SK57999A3 - Nucleic acid and amino acid sequences relating to helicobacter pylori and vaccine compositions thereof - Google Patents

Abstract

Recombinant or substantially pure preparations of H. pylori polypeptides are described. The nucleic acids encoding the polypeptides also are described. The H. pylori polypeptides are useful for diagnostics and vaccine compositions, wherein the figure depicts an amino acid sequence alignment of five H. pylori proteins.

Description

Helicobacter pylori nucleic acids and amino acid sequences and vaccine compositions containing them

BACKGROUND OF THE INVENTION

Helicobacter pylon is a gram-negative, microaerophilic, S-shaped bacterium that has been discovered and cultured from a biopsy sample of the human stomach. (Warren, J.R. and B. Marshall, (1983) Lancet 1: 1273-1275; and Marshall et al., (1984) Microbios Lett. 25: 83-88). H. pylon was strongly associated with chronic gastritis and duodenal ulcer disease. (Rathbone et al., (1986) Gut 27: 635-641). In addition, evidence is collected about the etiological role of H. pylori in non-ulcer dyspepsia, gastric ulcer disease and gastric adenocarcinoma. (Blaser, M.J., (1993) Trends Microbiol. 1: 255-260). Bacterial transmission occurs via the oral route and the risk of infection increases with age. (Taylor, D. N. and M.J. Blaser, (1991) Epidemiol. Rev 13: 42-50). H. pylori colonizes the mucosa of the human stomach and creates an infection that usually persists for decades. H. pylori infection is widespread worldwide. Infection in developed countries reaches more than 50% of the adult population, while infection in developing countries reaches 90% of adults over 20 years of age. (Hopkins, R.J. and J.G. Morris (1994) Am. J. Mes. 97: 265-277).

The bacterial factors necessary for colonization of the stomach environment and for virulence of the pathogen are poorly understood. Examples of alleged virulent factors include the following: urease, an enzyme that may play a role in neutralizing gastric acid pH (Eaton et al., (1991) Infect. Immunol. 59: 2470-2475; Ferrero, RL and A. Lee (1991) Microb Ecol.Hlth Dis 4: 121-134; Labigne et al., (1991) J. Bacteriol 173: 1920-1931); bacterial flagellins responsible for moving through the mucosal layer (Hazeil et al., (1986) J. Inf. Dis. 153: 658-663; Leying et al., (1992) Mol. Microbiol. 6: 2863-2874; and Haas et al., (1993 (Mol. Microbiol. 8: 753-760); Vac A, a bacterial toxin that induces the formation of intracellular vacuoles in epithelial cells (Schmitt, W and R. Haas, (1994) Molecular Microbiol. 12 ( 2): 307-319) and several gastric, tissue-specific adhesins (Boren et al., (1993) Science 262: 1892-1895; Evans et al., (1993) J. Bacteriol. 175: 674-683; and Falk et al., (1993) Proc. Natl. Acad. Sci USA 90: 2035-203).

A number of therapeutic agents that kill H. pylon infections in vitro are currently available. (Huesca et al., (1993) Coll. Bact. 280: 244-252; Hopkins, R.J. and J.G. Morris, supra). However, many of these drugs are less than optimally effective in vivo due to bacterial resistance, altered drug distribution, due to patient inconsistency or poor drug availability. (Hopkins, R.J. and J.G. Morris, supra). Part of the standard regimen used to treat H. pylon infection is treatment with antibiotics in combination with bismuth. (Malfertheiner, P. and J. E. Dominguez-Munoz (1993) Clinical Therapeutics 15 Supp. B: 37-48). Recently, combinations of proton pump inhibitors and one antibiotic have been shown to improve duodenal ulcer disease. (Malfertheiner, P. and J. E. Dominguez Munoz, supra). However, methods using antibiotic agents can cause the problem of the appearance of bacterial strains that are resistant to these agents. (Hopkins, R.J. and J.G. Morris, supra). These limitations demonstrate the need for new, more effective methods for controlling H. pylori infections in vivo. In particular, it is highly desirable to design new vaccines that can prevent infection by bacteria.

SUMMARY OF THE INVENTION

The present invention relates to novel genes, e.g. genes encoding polypeptides such as bacterial surface proteins, from Helicobacter pylori (H. pylori), and other related genes, their products and uses thereof. The nucleic acids and peptides of the present invention are useful for the diagnosis and therapy of H. pylori and other Helicobacter species. They can also be used to detect the presence of H. pylori and other Helicobacter species in a sample; and for screening for compounds having the ability to interfere with or inhibit H. pylori infection in the life cycle of H. pylori. More specifically, the present invention provides nucleic acid compositions corresponding to the entire coding sequence of H. pylori proteins, including surface or secreted proteins or portions thereof, nucleic acids capable of binding mRNA from H. pylori proteins, to block protein translation, and methods for producing H. pylori proteins or parts thereof using peptide synthesis techniques and recombinant DNA techniques. The invention also relates to antibodies and nucleic acids that can be used as probes to detect H. pylori infection. In addition, the present invention encompasses vaccine compositions and methods of protecting or treating H. pylori infection.

BRIEF DESCRIPTION OF THE DRAWINGS

Figure 1 shows the amino acid sequence alignment of the five H. pylori proteins (shown by a single letter amino acid code and indicated by its amino acid sequence identification numbers; shown from N end to C end, left to right).

Figure 2 shows a portion of the N terminus of three H. pylori proteins (shown by a single letter amino acid code and labeled with its amino acid sequence identification numbers; shown from N terminus to C terminus, left to right).

DETAILED DESCRIPTION OF THE INVENTION

In one aspect, the invention relates to a recombinant or substantially pure preparation of a H. pylori polypeptide of SEQ. 98. The invention also encompasses a substantially pure nucleic acid encoding a H. pylori polypeptide of SEQ. 98, wherein such nucleic acid is contained in SEQ ID NO: 98. The H. pylori polypeptide sequences described herein are contained in the Sequence Listing and also the nucleic acids encoding the H. pylori polypeptides of the invention are contained in the Sequence Listing.

In another aspect, the invention relates to a substantially pure nucleic acid that encodes a H. pylori polypeptide having amino acid sequence # 1. 99 such as a nucleic acid comprising nucleotide sequence no. Second

In another aspect, the invention relates to a substantially pure nucleic acid that encodes a H. pylori polypeptide having amino acid sequence # 1. 100, such as a nucleic acid comprising nucleotide sequence no. Third

In another aspect, the invention relates to a substantially pure nucleic acid that encodes a H. pylori polypeptide having amino acid sequence # 1. 101, such as a nucleic acid comprising nucleotide sequence no. 4th

In another aspect, the invention relates to a substantially pure nucleic acid that encodes a H. pylori polypeptide having amino acid sequence # 1. 102, such as a nucleic acid comprising nucleotide sequence no. 5th

In another aspect, the invention relates to a substantially pure nucleic acid that encodes a H. pylori polypeptide having amino acid sequence # 1. 103, such as a nucleic acid comprising nucleotide sequence no. 6th

In another aspect, the invention relates to a substantially pure nucleic acid that encodes a H. pylori polypeptide having amino acid sequence # 1. 104, such as a nucleic acid comprising nucleotide sequence no. 7th

In another aspect, the invention relates to a substantially pure nucleic acid that encodes an H. py / ori polypeptide having amino acid sequence # 1. 105, such as a nucleic acid comprising nucleotide sequence no. 8th

In another aspect, the invention relates to a substantially pure nucleic acid that encodes an H. py / ori polypeptide having amino acid sequence # 1. 106, such as a nucleic acid comprising nucleotide sequence no. 9th

In another aspect, the invention relates to a substantially pure nucleic acid that encodes a H. pylori polypeptide having amino acid sequence # 1. 107, such as a nucleic acid comprising nucleotide sequence no. 10th

In another aspect, the invention relates to a substantially pure nucleic acid that encodes a H. pylori polypeptide having amino acid sequence # 1. 108, such as a nucleic acid comprising nucleotide sequence no. 11th

In another aspect, the invention relates to a substantially pure nucleic acid that encodes a H. pylori polypeptide having amino acid sequence # 1. 109, such as a nucleic acid comprising nucleotide sequence no. 12th

In another aspect, the invention relates to a substantially pure nucleic acid that encodes an H. py / ori polypeptide having amino acid sequence # 1. 110, such as a nucleic acid comprising nucleotide sequence no. 13th

In another aspect, the invention relates to a substantially pure nucleic acid that encodes a H. pylori polypeptide having amino acid sequence # 1. 111, such as a nucleic acid comprising nucleotide sequence no. 14th

In another aspect, the invention relates to a substantially pure nucleic acid that encodes a H. pylori polypeptide having amino acid sequence # 1. 112, such as a nucleic acid comprising nucleotide sequence no. 15th

In another aspect, the invention relates to a substantially pure nucleic acid that encodes an H. py / ori polypeptide having amino acid sequence # 1. 113, such as a nucleic acid comprising nucleotide sequence no. 16th

In another aspect, the invention relates to a substantially pure nucleic acid that encodes a H. pylori polypeptide having amino acid sequence # 1. 114, such as a nucleic acid comprising nucleotide sequence no. 17th

In another aspect, the invention relates to a substantially pure nucleic acid that encodes a H. pylori polypeptide having amino acid sequence # 1. 115, such as a nucleic acid comprising nucleotide sequence no. 18th

In another aspect, the invention relates to a substantially pure nucleic acid that encodes an H. py / ori polypeptide having amino acid sequence # 1. 116, such as a nucleic acid comprising nucleotide sequence no. 19th

In another aspect, the invention relates to a substantially pure nucleic acid that encodes a H. pylori polypeptide having amino acid sequence # 1. 117, such as a nucleic acid comprising nucleotide sequence no. 20th

In another aspect, the invention relates to a substantially pure nucleic acid that encodes a H. pylori polypeptide having amino acid sequence # 1. 118, such as a nucleic acid comprising nucleotide sequence no. 21st

In another aspect, the invention relates to a substantially pure nucleic acid that encodes an H. py / ori polypeptide having amino acid sequence # 1. 119, such as a nucleic acid comprising nucleotide sequence no. 22nd

In another aspect, the invention relates to a substantially pure nucleic acid that encodes a H. pylori polypeptide having amino acid sequence # 1. 120, such as a nucleic acid comprising nucleotide sequence no. 23rd

In another aspect, the invention relates to a substantially pure nucleic acid that encodes a H. pylori polypeptide having amino acid sequence # 1. 121, such as a nucleic acid comprising nucleotide sequence no. 24th

In another aspect, the invention relates to a substantially pure nucleic acid that encodes a H. pylori polypeptide having amino acid sequence # 1. 122, such as a nucleic acid comprising nucleotide sequence no. 25th

In another aspect, the invention relates to a substantially pure nucleic acid that encodes a H. pylori polypeptide having amino acid sequence # 1. 123, such as a nucleic acid comprising nucleotide sequence no. 26th

In another aspect, the invention relates to a substantially pure nucleic acid that encodes a H. pylori polypeptide having amino acid sequence # 1. 124, such as a nucleic acid comprising nucleotide sequence no. 27th

In another aspect, the invention relates to a substantially pure nucleic acid that encodes a H. pylori polypeptide having amino acid sequence # 1. 125, such as a nucleic acid comprising nucleotide sequence no. 28th

In another aspect, the invention relates to a substantially pure nucleic acid that encodes a H. pylori polypeptide having amino acid sequence # 1. 126, such as a nucleic acid comprising nucleotide sequence no. 29th

In another aspect, the invention relates to a substantially pure nucleic acid that encodes a H. pylori polypeptide having amino acid sequence # 1. 127, such as a nucleic acid comprising nucleotide sequence no. 30th

In another aspect, the invention relates to a substantially pure nucleic acid that encodes an H. pylon polypeptide having amino acid sequence # 1. 128, such as a nucleic acid comprising nucleotide sequence no. 31st

In another aspect, the invention relates to a substantially pure nucleic acid that encodes an H. pylon polypeptide having amino acid sequence # 1. 129, such as a nucleic acid comprising nucleotide sequence no. 32nd

In another aspect, the invention relates to a substantially pure nucleic acid that encodes an H. pylon polypeptide having amino acid sequence # 1. 130, such as a nucleic acid comprising nucleotide sequence no. 33rd

In another aspect, the invention relates to a substantially pure nucleic acid that encodes an H. pylon polypeptide having amino acid sequence # 1. 131, such as a nucleic acid comprising nucleotide sequence no. 34th

In another aspect, the invention relates to a substantially pure nucleic acid that encodes a H. pylori polypeptide having amino acid sequence # 1. 132, such as a nucleic acid comprising nucleotide sequence no. 35th

In another aspect, the invention relates to a substantially pure nucleic acid that encodes a H. pylori polypeptide having amino acid sequence # 1. 133, such as a nucleic acid comprising nucleotide sequence no. 36th

In another aspect, the invention relates to a substantially pure nucleic acid that encodes a H. pylori polypeptide having amino acid sequence # 1. 134, such as a nucleic acid comprising nucleotide sequence no. 37th

In another aspect, the invention relates to a substantially pure nucleic acid that encodes a H. pylori polypeptide having amino acid sequence # 1. 135, such as a nucleic acid comprising nucleotide sequence no. 38th

In another aspect, the invention relates to a substantially pure nucleic acid that encodes a H. pylori polypeptide having amino acid sequence # 1. 136, such as a nucleic acid comprising nucleotide sequence no. 39th

In another aspect, the invention relates to a substantially pure nucleic acid that encodes an H. pylon polypeptide having amino acid sequence # 1. 137, such as a nucleic acid comprising the nucleotide sequence δ. 40th

In another aspect, the invention relates to a substantially pure nucleic acid that encodes an H. pylon polypeptide having amino acid sequence # 1. 138, such as a nucleic acid comprising nucleotide sequence no. 41st

In another aspect, the invention relates to a substantially pure nucleic acid that encodes an H. py / ori polypeptide having amino acid sequence # 1. 139, such as a nucleic acid comprising nucleotide sequence no. 42nd

In another aspect, the invention relates to a substantially pure nucleic acid that encodes a H. pylori polypeptide having amino acid sequence # 1. 140, such as a nucleic acid comprising nucleotide sequence no. 43rd

In another aspect, the invention relates to a substantially pure nucleic acid that encodes an H. py / orz polypeptide having amino acid sequence # 1. 141, such as a nucleic acid comprising nucleotide sequence no. 44th

In another aspect, the invention relates to a substantially pure nucleic acid that encodes a H. pylori polypeptide having amino acid sequence # 1. 142, such as a nucleic acid comprising nucleotide sequence no. 45th

In another aspect, the invention relates to a substantially pure nucleic acid that encodes a H. pylori polypeptide having amino acid sequence # 1. 143, such as a nucleic acid comprising nucleotide sequence no. 46th

In another aspect, the invention relates to a substantially pure nucleic acid that encodes a H. pylori polypeptide having amino acid sequence # 1. 144, such as a nucleic acid comprising nucleotide sequence no. 47th

In another aspect, the invention relates to a substantially pure nucleic acid that encodes a H. pylori polypeptide having amino acid sequence # 1. 145, such as a nucleic acid comprising nucleotide sequence no. 43rd

g

In another aspect, the invention relates to a substantially pure nucleic acid that encodes an H. pylon polypeptide having amino acid sequence # 1. 146, such as a nucleic acid comprising nucleotide sequence no. 49th

In another aspect, the invention relates to a substantially pure nucleic acid that encodes a H. pylori polypeptide having amino acid sequence # 1. 147, such as a nucleic acid comprising nucleotide sequence no. 50th

In another aspect, the invention relates to a substantially pure nucleic acid that encodes an H. py / ori polypeptide having amino acid sequence # 1. 148, such as a nucleic acid comprising nucleotide sequence no. 51st

In another aspect, the invention relates to a substantially pure nucleic acid that encodes an H. py / ori polypeptide having amino acid sequence # 1. 149, such as a nucleic acid comprising nucleotide sequence no. 52nd

In another aspect, the invention relates to a substantially pure nucleic acid that encodes a H. pylori polypeptide having amino acid sequence # 1. 150, such as a nucleic acid comprising nucleotide sequence no. 53rd

In another aspect, the invention relates to a substantially pure nucleic acid that encodes a H. pylori polypeptide having amino acid sequence # 1. 151, such as a nucleic acid comprising nucleotide sequence no. 54th

In another aspect, the invention relates to a substantially pure nucleic acid that encodes a H. pylori polypeptide having amino acid sequence # 1. 152, such as a nucleic acid comprising nucleotide sequence no. 55th

In another aspect, the invention relates to a substantially pure nucleic acid that encodes a H. pylori polypeptide having amino acid sequence # 1. 153, such as a nucleic acid comprising nucleotide sequence no. 56th

In another aspect, the invention relates to a substantially pure nucleic acid that encodes an H. py / ori polypeptide having amino acid sequence # 1. 154, such as a nucleic acid comprising nucleotide sequence no. 57th

In another aspect, the invention relates to a substantially pure nucleic acid that encodes an H. py / ori polypeptide having amino acid sequence # 1. 155, such as a nucleic acid comprising nucleotide sequence no. 58th

In another aspect, the invention relates to a substantially pure nucleic acid that encodes an H. py / ori polypeptide having amino acid sequence # 1. 156, such as a nucleic acid comprising nucleotide sequence no. 59th

In another aspect, the invention relates to a substantially pure nucleic acid that encodes a H. pylori polypeptide having amino acid sequence # 1. 157, such as a nucleic acid comprising nucleotide sequence no. 60th

In another aspect, the invention relates to a substantially pure nucleic acid that encodes an H. py / ori polypeptide having amino acid sequence # 1. 158, such as a nucleic acid comprising nucleotide sequence no. 61st

In another aspect, the invention relates to a substantially pure nucleic acid that encodes an H. py / ori polypeptide having amino acid sequence # 1. 159, such as a nucleic acid comprising nucleotide sequence no. 62nd

In another aspect, the invention relates to a substantially pure nucleic acid that encodes a H. pyphor polypeptide having amino acid sequence # 1. 160, such as a nucleic acid comprising nucleotide sequence no. 63rd

In another aspect, the invention relates to a substantially pure nucleic acid that encodes a H. pyphor polypeptide having amino acid sequence # 1. 161, such as a nucleic acid comprising nucleotide sequence no. 64th

In another aspect, the invention relates to a substantially pure nucleic acid that encodes a H. pylori polypeptide having amino acid sequence # 1. 162, such as a nucleic acid comprising nucleotide sequence no. 65th

In another aspect, the invention relates to a substantially pure nucleic acid that encodes an H. py / ori polypeptide having amino acid sequence # 1. 163, such as a nucleic acid comprising nucleotide sequence no. 66th

In another aspect, the invention relates to a substantially pure nucleic acid that encodes an H. pylon polypeptide having amino acid sequence # 1. 164, such as a nucleic acid comprising nucleotide sequence no. 67th

In another aspect, the invention relates to a substantially pure nucleic acid that encodes a H. pylori polypeptide having amino acid sequence # 1. 165, such as a nucleic acid comprising nucleotide sequence no. 68th

In another aspect, the invention relates to a substantially pure nucleic acid that encodes a H. pylori polypeptide having amino acid sequence # 1. 166, such as a nucleic acid comprising nucleotide sequence no. 69th

In another aspect, the invention relates to a substantially pure nucleic acid that encodes a H. pylori polypeptide having amino acid sequence # 1. 167, such as a nucleic acid comprising nucleotide sequence no. 70th

In another aspect, the invention relates to a substantially pure nucleic acid that encodes a H. pylori polypeptide having amino acid sequence # 1. 168, such as a nucleic acid comprising nucleotide sequence no. 71st

In another aspect, the invention relates to a substantially pure nucleic acid that encodes a H. pylori polypeptide having amino acid sequence # 1. 169, such as a nucleic acid comprising nucleotide sequence no. 72nd

In another aspect, the invention relates to a substantially pure nucleic acid that encodes a H. pylori polypeptide having amino acid sequence # 1. 170, such as a nucleic acid comprising nucleotide sequence no. 73rd

In another aspect, the invention relates to a substantially pure nucleic acid that encodes a H. pylori polypeptide having amino acid sequence # 1. 171, such as a nucleic acid comprising nucleotide sequence no. 74th

In another aspect, the invention relates to a substantially pure nucleic acid that encodes a H. pylori polypeptide having amino acid sequence # 1. 172, such as a nucleic acid comprising nucleotide sequence no. 75th

In another aspect, the invention relates to a substantially pure nucleic acid that encodes a H. pylori polypeptide having amino acid sequence # 1. 173, such as a nucleic acid comprising nucleotide sequence no. 76th

In another aspect, the invention relates to a substantially pure nucleic acid that encodes a H. pylori polypeptide having amino acid sequence # 1. 174, such as a nucleic acid comprising nucleotide sequence no. 77th

In another aspect, the invention relates to a substantially pure nucleic acid that encodes a H. pylori polypeptide having amino acid sequence # 1. 175, such as a nucleic acid comprising nucleotide sequence no. 78th

In another aspect, the invention relates to a substantially pure nucleic acid that encodes a H. pylori polypeptide having amino acid sequence # 1. 176, such as a nucleic acid comprising nucleotide sequence no. 79th

In another aspect, the invention relates to a substantially pure nucleic acid that encodes a H. pylori polypeptide having amino acid sequence # 1. 177, such as a nucleic acid comprising nucleotide sequence no. 80th

In another aspect, the invention relates to a substantially pure nucleic acid that encodes a H. pylori polypeptide having amino acid sequence # 1. 178, such as a nucleic acid comprising nucleotide sequence no. 81st

In another aspect, the invention relates to a substantially pure nucleic acid that encodes a H. pylori polypeptide having amino acid sequence # 1. 179, such as a nucleic acid comprising nucleotide sequence no. 82nd

In another aspect, the invention relates to a substantially pure nucleic acid that encodes a H. pylori polypeptide having amino acid sequence # 1. 180, such as a nucleic acid comprising nucleotide sequence no. 83rd

In another aspect, the invention relates to a substantially pure nucleic acid that encodes a H. pylori polypeptide having amino acid sequence # 1. 181, such as a nucleic acid comprising nucleotide sequence no. 84th

In another aspect, the invention relates to a substantially pure nucleic acid that encodes an H. py / οπ polypeptide having amino acid sequence # 1. 182, such as a nucleic acid comprising nucleotide sequence no. 85th

In another aspect, the invention relates to a substantially pure nucleic acid that encodes a H. pylori polypeptide having amino acid sequence # 1. 183, such as a nucleic acid comprising nucleotide sequence no. 86th

In another aspect, the invention relates to a substantially pure nucleic acid that encodes a H. pylori polypeptide having amino acid sequence # 1. 184, such as a nucleic acid comprising nucleotide sequence no. 87th

In another aspect, the invention relates to a substantially pure nucleic acid that encodes a H. pylori polypeptide having amino acid sequence # 1. 185, such as a nucleic acid comprising nucleotide sequence no. 88th

In another aspect, the invention relates to a substantially pure nucleic acid that encodes a H. pylori polypeptide having amino acid sequence # 1. 186, such as a nucleic acid comprising nucleotide sequence no. 89th

In another aspect, the invention relates to a substantially pure nucleic acid that encodes a H. pylori polypeptide having amino acid sequence # 1. 187, such as a nucleic acid comprising nucleotide sequence no. 90th

In another aspect, the invention relates to a substantially pure nucleic acid that encodes a H. pylori polypeptide having amino acid sequence # 1. 188, such as a nucleic acid comprising nucleotide sequence no. 91st

In another aspect, the invention relates to a substantially pure nucleic acid that encodes a H. pylori polypeptide having amino acid sequence # 1. 189, such as a nucleic acid comprising nucleotide sequence no. 92nd

In another aspect, the invention relates to a substantially pure nucleic acid that encodes a H. pylori polypeptide having amino acid sequence # 1. 190, such as a nucleic acid comprising nucleotide sequence no. 93rd

In another aspect, the invention relates to a substantially pure nucleic acid that encodes a H. pylori polypeptide having amino acid sequence # 1. 191, such as a nucleic acid comprising nucleotide sequence no. 94th

In another aspect, the invention relates to a substantially pure nucleic acid that encodes a H. pylori polypeptide having amino acid sequence # 1. 192, such as a nucleic acid comprising nucleotide sequence no. 95th

In another aspect, the invention relates to a substantially pure nucleic acid that encodes an H. py / ori polypeptide having amino acid sequence # 1. 193, such as a nucleic acid comprising nucleotide sequence no. 96th

In another aspect, the invention relates to a substantially pure nucleic acid that encodes a H. pylori polypeptide having amino acid sequence # 1. 194, such as a nucleic acid comprising nucleotide sequence no. 97th

In another aspect, the invention relates to an isolated nucleic acid having a nucleotide sequence that encodes an H. pylori polypeptide at least about 60% homologous to an amino acid sequence selected from the group consisting of SEQ ID NO: 2. 98 to 194. In a preferred embodiment, the isolated nucleic acid comprises a nucleotide sequence selected from the group consisting of SEQ ID NOs. 1 to 97 or their additions.

In another aspect, the invention relates to an isolated nucleic acid having a nucleotide sequence that encodes an H. pylori polypeptide selected from a ski-in consisting of SEQ ID NO: 2. 98 to 194.

In another aspect, the invention relates to an isolated nucleic acid that encodes an H. pylori polypeptide having a nucleotide sequence of at least about 60% homologous to a nucleotide sequence selected from the group consisting of SEQ ID NO: 2. 1 to 97 or their supplement.

In another aspect, the invention relates to an isolated nucleic acid molecule that encodes an H. pylori polypeptide with a nucleotide sequence that hybridizes under stringent hybridization conditions to a nucleic acid molecule with a nucleotide sequence selected from the group consisting of SEQ ID NO: 2. 1 to 97 or their supplement.

In another aspect, the invention relates to an isolated nucleic acid having a nucleotide sequence of at least 8 nucleotides in length, which hybridizes under stringent hybridization conditions to a nucleic acid with a nucleotide sequence selected from the group consisting of SEQ ID NO: 2. 1 to 97 or their supplement.

Particularly preferred is an isolated nucleic acid having a nucleotide sequence encoding a H. pylori cell envelope polypeptide or a fragment thereof, wherein the nucleic acid is selected from the group consisting of SEQ ID NO: 2. 63, no. 7, no. 8, no. 9, no. 13, no. 14, no. 23, no. 24, no. 27, no. 28, no. 50, no. 51, no. 61, no. 79, no. 80.

no. 84, no. 85, no. 91, no. 94, no. 5, no. 11, no. 26, no. 36, no. 42, no. 52, no. 22, no. 29, no. 30, no. 65, no. 66, no. 48, no. 49, no. 17, no. 18, no. 19, no. 43, no. 44, no. 38, no. 39, no. 1, no. 2, no. 6, no.

34, no. 35, no. 60, no. 69 and no. 83 or their supplements.

In one embodiment, the H. pylori cell envelope polypeptide or fragment thereof is a polypeptide associated with H. pylori flagellins or a fragment thereof encoded by a nucleic acid of nucleotide sequence # 1. 63 or its supplement.

In another embodiment, the H. pylori cell envelope polypeptide or fragment thereof is an H. pylori inner membrane polypeptide or fragment thereof encoded by a nucleic acid selected from the group consisting of SEQ ID NO: 2. 48, n.49, n. 17, no. 18, no. 19, No.43, No.44, No.38 and No.39, or a supplement thereof.

In another embodiment, the H. pylori inner membrane polypeptide or fragment thereof is an H. pylori polypeptide or fragment thereof involved in transport encoded by a nucleic acid selected from the group consisting of SEQ ID NO: 2. 48, n.49, n. 17, no. 18, no. 19, No.43 and No.44 or their supplement.

In another embodiment, the H. pylori cell envelope polypeptide or fragment thereof is an H. pylori outer membrane polypeptide or fragment thereof encoded by a nucleic acid selected from the group consisting of SEQ. 7, no. 8, no. 9, no. 13, no. 14, no. 23, no. 24, no. 27, no. 28, no. 50, no. 51, no. 61, no. 79, no. 80, no. 84, no. 85.

no. 91, no. 94, no. 5, no. 11, no. 26, no. 36, no. 42, no. 52, no. 22, no. 29, no. 30, no. 65 and no. 66 or their supplement.

In another embodiment, the H. pylori outer membrane polypeptide or fragment thereof is a phenylalanine-terminal H. pylori polypeptide or a fragment thereof encoded by a nucleic acid selected from the group consisting of SEQ ID NO: 2. 7, no. 8, no. 9, no. 11, no. 13, no. 14, no. 23, no. 24, no. 26, no. 27, no. 28, no. 36, no. 42, no. 50, no. 51, no. 52, no. 61, no. 79, no. 80, no. 84, no. 85, no. 91 and no. 94 or their supplement.

In another embodiment, the H. pylori outer membrane polypeptide or fragment thereof is a H. pylori polypeptide with a terminal phenylalanine residue and a terminal tyrosine cluster, or a fragment thereof encoded by a nucleic acid selected from the group consisting of SEQ ID NO: 2. 11, no. 26, no. 36, no. 42 and no. 52 or their supplement.

Particularly preferred is an isolated nucleic acid having a nucleotide sequence encoding a H. pylori cell envelope polypeptide or fragment thereof, wherein the nucleic acid is selected from the group consisting of SEQ ID NO: 2. 160, no. 104, no. 105, no. 106, no. 110, no. 111, no. 120, no. 121, no. 124, no. 125, no. 147, no. 148, no. 158, no. 176, no. 177, no. 181, no. 182, no. 188, no. 191, no. 102, no. 108, no. 123, no. 133, no. 139, no. 149, no. 119, no. 126, no. 127, no. 162, no. 163, no. 145, no. 146, no. 114, no. 115, no. 116, no. 140, no. 141, no. 135, no. 136, no. 98, no. 99, no. 103, no. 131, no. 132, no. 157, no. 166 and no. 180th

In another embodiment, the H. pylori cell envelope polypeptide or fragment thereof is a polypeptide associated with H. pylori flagellins or a fragment thereof having amino acid sequence # 1. 160th

In another embodiment, the H. pylori cell envelope polypeptide or fragment thereof is H. pylori inner membrane polypeptide or fragment thereof selected from the group consisting of SEQ ID NO: 2. 145, no. 146, no. 114, no. 115, no. 116, no. 140, no. 141, no. 135 and no. 136th

In another embodiment, the H. pylori inner membrane polypeptide or fragment thereof is a H. pylori polypeptide or fragment thereof involved in transport selected from the group consisting of SEQ ID NO: 2. 145, no. 146, no. 114, no. 115, no. 116, no. 140 and no. 141st

In another embodiment, the H. pylori cell envelope polypeptide or fragment thereof is an H. pylori outer membrane polypeptide or fragment thereof selected from the group consisting of SEQ ID NO: 2. 104, no. 105, no. 106, no. 110, no. 111, no. 120, no. 121, no. 124, no. 125, no. 147, no. 148, no. 158, no. 176, no. 177, no. 181, no. 182, no. 188, no. 191, no. 102, no. 108, no. 123, no. 133, no. 139, no. 149, no. 119, no. 126, no. 127, no. 162 and no. 163rd

In another embodiment, the H. pylori outer membrane polypeptide or fragment thereof is a phenylalanine-terminal H. pylori polypeptide or a fragment thereof selected from the group consisting of SEQ ID NO: 2. 104, no. 105, no. 106, no. 108, no. 110, no. 111, no. 120, no. 121, no. 123, no. 124, no. 125, no. 133, no. 139, no. 147, no. 148, no. 149, no. 158, no. 176, no. 177, no. 181, no. 182, no. 188 and no. 191st

In another embodiment, the H. pylori outer membrane polypeptide or fragment thereof is a H. pylori polypeptide with a terminal phenylalanine residue and a terminal tyrosine cluster, or a fragment thereof selected from the group consisting of SEQ ID NO: 2. 108, no. 123, no. 133, no. 139 and no. 149th

Particularly preferred is an isolated nucleic acid having a nucleotide sequence encoding a cytoplasmic H. pylori polypeptide or fragment thereof, wherein the nucleic acid is selected from the group consisting of SEQ ID NO: 2. 57, no. 58, no. 86, no. 87, no. 88, no. 89, no. 92 and no. 93, or a supplement thereof.

In one embodiment, the cytoplasmic H. pylori polypeptide or fragment thereof is H. pylori polypeptide or fragment thereof involved in the translation of mRNA, wherein the nucleic acid is selected from the group consisting of SEQ ID NO: 2. 57 and no. 58 or their supplement.

In another embodiment, the cytoplasmic H. pylori polypeptide or fragment thereof is H. pylori polypeptide or fragment thereof involved in genomic replication, transcription, recombination, and repair, wherein the nucleic acid is selected from the group consisting of SEQ ID NO: 2. 86 and no. 87 or their supplement.

Particularly preferred is an isolated nucleic acid having a nucleotide sequence encoding a cytoplasmic H. pylori polypeptide, or fragment thereof, selected from the group consisting of SEQ ID NO: 2. 154, no. 155, no. 183, no. 184, no. 185, no. 186, no. 189 and no. 190th

In one embodiment, the cytoplasmic H. pylori polypeptide or fragment thereof is H. pylori polypeptide or fragment thereof involved in mRNA translation selected from the group consisting of SEQ ID NO: 2. 154 and no. 155th

In another embodiment, the cytoplasmic H. pylori polypeptide or fragment thereof is an H. pylori polypeptide or fragment thereof involved in genomic replication, transcription, recombination, and repair selected from the group consisting of SEQ ID NO: 2. 183 and no. 184th

Particularly preferred is an isolated nucleic acid having a nucleotide sequence encoding a H. pylori secreted polypeptide or fragment thereof, wherein the nucleic acid is selected from the group consisting of SEQ ID NO: 2. 3, no. 4, no. 10, no. 12, no. 20, no. 25, no. 31, no. 32, no. 45, no. 46, no. 53 č. 64, no. 67, no. 70, no. 77, no. 78, no. 81, no. 82, no. 90, no. 95 and no. 97 or their supplement.

Particularly preferred is an isolated nucleic acid having a nucleotide sequence encoding a H. pylori secreted polypeptide or a fragment thereof selected from the group consisting of SEQ ID NO: 2. 100, no. 101, no. 107, no. 109, no. 117, no. 122, no. 128, no. 129, no. 142, no. 143, no. 150 č. 161, no. 164, no. 167, no. 174, no. 175, no. 178, no. 179, no. 187, no. 192 and no. 194th

Particularly preferred is an isolated nucleic acid having a nucleotide sequence encoding a H. pylori cell polypeptide or a fragment thereof, wherein the nucleic acid is selected from the group consisting of SEQ ID NO: 2. 15, no. 16, no. 21, no. 33, no. 37, no. 40, no. 41, no. 47, no. 54, no. 55, no. 56 č. 59, no. 62, no. 68, no. 71, no. 72, no. 73, no. 74, no. 75, no. 76 and no. 96 or their supplement.

Particularly preferred is an isolated nucleic acid having a nucleotide sequence encoding a H. pylori cell polypeptide or a fragment thereof selected from the group consisting of SEQ ID NO: 2. 112, no. 113, no. 118, no. 130, no. 134, no. 137, no. 138, c. 144, no. 151, no. 152, no. 153 č. 156, no. 159, ó. 165, no. 168, ó. 169, no. 170, no. 171, no. 172, no. 173 and no. 193rd

In another aspect, the invention relates to a probe having a nucleotide sequence consisting of at least 8 nucleotides with a nucleotide sequence selected from the group consisting of SEQ ID NO: 2. 1 - no. 97 or their supplement.

In another aspect, the invention relates to an isolated H. pylori polypeptide having an amino acid sequence of at least about 60% homologous to an H. pylori polypeptide selected from the group consisting of SEQ ID NO: 2. 98 to no. 194th

In another aspect, the invention relates to an isolated H. pylori polypeptide that is encoded by a nucleic acid having a nucleotide sequence of at least about 60% homologous to a nucleotide sequence selected from the group consisting of SEQ ID NO: 2. 1 to no. 97. In one embodiment, the isolated H. pylori polypeptide is encoded by a nucleotide sequence selected from the group consisting of SEQ ID NOs. 1 to no. 97th

In another aspect, the invention relates to an isolated H. pylori polypeptide that is encoded by a nucleic acid that hybridizes under stringent hybridization conditions to a nucleic acid selected from the group consisting of SEQ ID NO: 2. 1 to 97 or their additions.

In another aspect, the invention relates to an isolated H. pylori polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO: 2. 97 to 194.

Particularly preferred is an isolated H. pylori cell envelope polypeptide, or fragment thereof, wherein the polypeptide is selected from the group consisting of SEQ ID NO: 2. 160, no. 104, no. 105, no. 106, no. 110, no. 111, no. 120, no. 121, no. 124, no. 125, no. 147, no. 148, no. 158, no. 176, no. 177, no. 181, no. 182, no. 188, no. 191, no. 102, no. 108, no. 123, no.

133, no. 139, no. 149, no. 119, no. 126, no. 127, no. 162, no. 163, no. 145, no. 146, no. 114, no. 115, no. 116, no. 140, no. 141, no. 135, no. 136, no. 98, no. 99, no. 103, no. 131, no. 132, no. 157, no. 166 and no. 180th

In one embodiment, the H. pylori cell envelope polypeptide or fragment thereof is a polypeptide associated with H. pylori flagellins or a fragment thereof having amino acid sequence # 1. 160th

In another embodiment, the H. pylori cell envelope polypeptide or fragment thereof is H. pylori inner membrane polypeptide or fragment thereof selected from the group consisting of SEQ ID NO: 2. 145, no. 146, no. 114, no. 115, no. 116, no. 140, no. 141, no. 135 and no. 136th

In another embodiment, the H. pylori inner cell membrane polypeptide or fragment thereof is a H. pylori polypeptide or transport fragment thereof selected from the group consisting of SEQ ID NO: 2. 145, no. 146, no. 114, no. 115, no. 116, no. 140, no. 141, no. 135 and no. 136th

In another embodiment, the H. pylori cell envelope polypeptide or fragment thereof is an H. pylori outer membrane polypeptide or fragment thereof selected from the group consisting of SEQ ID NO: 2. 104, no. 105, no. 106, no. 110, no. 111, no. 120, no. 121, no. 124, no. 125, no. 147, no. 148, no. 158, no. 176, no. 177, no. 181, no. 182, no. 188, no. 191, no. 102, no. 108, no. 123, no. 133, no. 139, no. 149, no. 119, no. 126, no. 127, no. 162 and no. 163rd

In another embodiment, the H. pylori outer membrane polypeptide or fragment thereof is a phenylalanine-terminal H. pylori polypeptide or a fragment thereof selected from the group consisting of SEQ ID NO: 2. 104, no. 105, no. 106, no. 108, no. 110, no. 111, no. 120, no. 121, no. 123, no. 124, no. 125, no. 133, no. 139, no. 147, no. 148, no. 149, no. 158, no. 176, no. 177, no. 181, no. 182, no. 188 and no. 191st

In another embodiment, the H. pylori outer membrane polypeptide or fragment thereof is a H. pylori polypeptide with a terminal phenylalanine residue and a terminal tyrosine cluster, or a fragment thereof selected from the group consisting of SEQ ID NO: 2. 108, no. 123, no. 133, no. 139 and no. 149th

Particularly preferred is an isolated H. pylori cell envelope polypeptide or fragment thereof, wherein the polypeptide is encoded by a nucleic acid selected from the group consisting of SEQ ID NO: 2. 63, no. 7, no. 8, no. 9, no. 13, no. 14, no. 23, no. 24, no. 27, no. 28, no. 50, no. 51, no. 61, no. 79, no. 80, no. 84, no. 85, no. 91, no. 94, no. 5, no. 11, no. 26, no. 36, no. 42, no. 52, no. 22, no. 29, no. 30, no. 65, no. 66, no. 48, no. 49, no. 17, no. 18, no. 19, no. 43, no. 44, no. 38, no. 39, no. 1, no. 2, no. 6, no. 34, no. 35, no. 60, no. 69 and no. 83rd

In one embodiment, the H. pylori cell envelope polypeptide or fragment thereof is a polypeptide associated with H. pylori flagellins or a fragment thereof encoded by a nucleic acid of nucleotide sequence # 1. 63rd

In another embodiment, the H. pylori cell envelope polypeptide or fragment thereof is an H. pylori inner membrane polypeptide or fragment thereof encoded by a nucleic acid selected from the group consisting of SEQ ID NO: 2. 48, no. 49, no. 17, no. 18, no. 19, no. 43, no. 44, no. 38 and no. 39th

In another embodiment, the H. pylori inner membrane polypeptide or fragment thereof is an H. pylori polypeptide or fragment thereof involved in transport encoded by a nucleic acid selected from the group consisting of SEQ ID NO: 2. 48, no. 49, no. 17, no. 18, no. 19, no. 43 and no. 44th

In another embodiment, the H. pylori cell envelope polypeptide or fragment thereof is an H. pylori outer membrane polypeptide or fragment thereof encoded by a nucleic acid selected from the group consisting of SEQ. 7, no. 8, no. 9, no. 13, no. 14, no. 23, no. 24, no. 27, no. 28, no. 50, no. 51, no. 61, no. 79, no. 80, no. 84, no. 85, no. 91, no. 94, no. 5, no. 11, no. 26, no. 36, no. 42, no. 52, no. 22, no. 29, no. 30, no. 65 and no. 66th

In another embodiment, the H. pylori outer membrane polypeptide or fragment thereof is a phenylalanine-terminal H. pylori polypeptide or a fragment thereof encoded by a nucleic acid selected from the group consisting of SEQ ID NO: 2. 7, no. 8, no. 9, no. 11, no. 13, no. 14, no. 23, no. 24, no. 26, no. 27, no. 28, no. 36, no. 42, no. 50, no. 51, no. 52, no. 61, no. 79, no. 80, no. 84, no. 85, no. 91 and no. 94th

In another embodiment, the H. pylori outer membrane polypeptide or fragment thereof is a H. pylori polypeptide with a terminal phenylalanine residue and a C22 terminal tyrosine cluster or a fragment thereof encoded by a nucleic acid selected from the group consisting of SEQ ID NO: 2. 11, no. 26, no. 36, no. 42 and no. 52nd

Particularly preferred is an isolated cytoplasmic H. pylori polypeptide or fragment thereof, wherein the polypeptide is selected from the group consisting of SEQ ID NO: 2. 154, no. 155, no. 183, no. 184, no. 185, no. 186, no. 189 and no. 190th

In another embodiment, the cytoplasmic H. pylori polypeptide or fragment thereof is H. pylori polypeptide or fragment thereof involved in mRNA translation selected from the group consisting of SEQ ID NO: 2. 154 and no. 155th

In another embodiment, the cytoplasmic H. pylori polypeptide or fragment thereof is an H. pylori polypeptide or fragment thereof involved in genomic replication, transcription, recombination, and repair selected from the group consisting of SEQ ID NO: 2. 183 and no. 184th

Particularly preferred is an isolated cytoplasmic H. pylori polypeptide or fragment thereof, wherein the polypeptide is encoded by a nucleic acid selected from the group consisting of SEQ ID NO: 2. 57, no. 58, no. 86, no. 87, no. 88, no. 89, no. 92 and no. 93rd

In one embodiment, the cytoplasmic H. pylori polypeptide or fragment thereof is an H. pylori polypeptide or fragment thereof involved in mRNA translation, wherein the polypeptide is selected from the group consisting of SEQ ID NO: 2. 57 and no. 58th

In another embodiment, the cytoplasmic H. pylori polypeptide or fragment thereof is H. pylori polypeptide or fragment thereof involved in genomic replication, transcription, and repair, wherein the polypeptide is encoded by a nucleic acid selected from the group consisting of SEQ ID NO: 2. 86 and no. 87th

Particularly preferred is an isolated H. pylori cell polypeptide or fragment thereof, wherein the polypeptide is selected from the group consisting of SEQ ID NO: 2.

112, no. 113, no. 118, no. 130, no. 134, no. 137, no. 138, no. 144, no. 151, no. 152, no. 153 č. 156, no. 159, no. 165, no. 168, no. 169, no. 170, no. 171, no. 172, no. 173 and no. 193rd

Particularly preferred is an isolated H. pylori cell polypeptide or fragment thereof, wherein the polypeptide is encoded by a nucleic acid selected from the group consisting of SEQ ID NO: 2. 15, no. 16, no. 21, no. 33, no. 37, no. 40, no. 41, no. 47, no. 54, no. 55, no. 56 č. 59, no. 62, no. 68, no. 71, no. 72, no. 73, no. 74, no. 75, no. 76 and no. 96th

Particularly preferred is an isolated H. pylori secreted polypeptide or fragment thereof, wherein the polypeptide is selected from the group consisting of SEQ ID NO: 2. 100, no. 101, no. 107, no. 109, no. 117, no. 122, no. 128, no. 129, no. 142, no. 143, no. 150 č. 161, no. 164, no. 167, no. 174, no. 175, no. 178, no. 179, no. 187, no. 192 and no. 194th

Particularly preferred is an isolated H. pylori secreted polypeptide or fragment thereof, wherein the polypeptide is encoded by a nucleic acid selected from the group consisting of SEQ ID NO: 2. 3, no. 4, no. 10, no. 12, no. 20, no. 25, no. 31, no. 32, no. 45, no. 46, no. 53 č. 64, no. 67, no. 70, no. 77, no. 78, no. 81, no. 82, no. 90, no. 95 and no. 97th

In another aspect, the invention relates to a chimeric H. pylori polypeptide comprising at least two H. pylori polypeptides or fragments thereof, wherein the polypeptides are encoded by nucleic acid sequences selected from the group of Seq. 1 to no. 97th

In another aspect, the invention relates to a chimeric H. pylori polypeptide consisting of at least two H. pylori polypeptides or fragments thereof, wherein the polypeptides are selected from the group consisting of SEQ ID NO: 2. 98 to no. 194th

In another aspect, the invention relates to a fusion protein consisting of a H. pylori polypeptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 2. 98 to no. 194 operably linked to a non-H. pylori polypeptide.

In another aspect, the invention relates to a vaccine composition for the prophylactic or therapeutic treatment of an H. pylori infection comprising an effective amount of at least one isolated nucleic acid of the invention.

In another aspect, the invention relates to a vaccine composition for the prophylactic or therapeutic treatment of an H. pylori infection comprising an effective amount of at least one H. pylori polypeptide of the invention.

The vaccine composition of the invention preferably further comprises a pharmaceutically acceptable carrier. In one embodiment, the pharmaceutically acceptable carrier comprises an adjuvant. In another embodiment, the pharmaceutically acceptable carrier comprises a delivery system, e.g. a live vector, e.g. bacteria or virus. In another embodiment, the pharmaceutically acceptable carrier comprises both an adjuvant and a delivery system.

In another aspect, the invention relates to a method of treating or reducing the risk of H. pylori infection in a subject. The method comprises administering to the subject a vaccine composition of the invention so as to treat or reduce the risk of H. pylori infection.

In another aspect, the invention relates to a method of making a vaccine composition of the invention. The method comprises combining at least one isolated H. pylori polypeptide or fragment thereof selected from the group consisting of SEQ ID NO: 2. 98 to no. 194 with a pharmaceutically acceptable carrier to form a vaccine formulation.

In another aspect, the invention relates to a method of making a vaccine composition of the invention. The method comprises culturing the cell under conditions that allow expression of a H. pylori polypeptide or fragment thereof selected from the group consisting of SEQ ID NO: 2. 98 to no. 194, isolating polypeptide II. pylori from the cell and combining at least one isolated H. pylori polypeptide or fragment thereof with a pharmaceutically acceptable carrier to form a vaccine preparation.

In another aspect, the invention relates to any single member of an H. pylori polypeptide, or a nucleic acid encoding such member from the above identified groups of H. pylori polypeptides.

In another aspect, the invention relates to nucleic acids capable of binding mRNA from H. pylori. Such a nucleic acid is capable of acting as an antisense nucleic acid to control the transcription of H. pylori mRNA. Another aspect relates to a nucleic acid that is capable of binding specifically to H. pylori nucleic acid. These nucleic acids are also referred to herein as complements and have utility as probes and capture agents.

In another aspect, the invention relates to an expression system comprising an open reading frame corresponding to a H. pylori nucleic acid. The nucleic acid further comprises a control sequence compatible with the intended host. The expression system is useful for producing polypeptides corresponding to H. pylori nucleic acid.

In another aspect, the invention relates to a cell transformed with an expression system to produce H. pylori polypeptides.

In another aspect, the invention relates to a method of generating antibodies against H. pylori polypeptides that are capable of binding specifically to H. pylori polypeptides. Such antibodies are used as reagents in immunoassays to evaluate the amount and distribution of H. pylori-specific antigens.

In another aspect, the invention relates to a method of making vaccines for immunizing individuals against H. pylori. The method of vaccination comprises: immunizing a subject with at least one H. pylori polypeptide of the present invention, e.g. a surface or secretory polypeptide, or an active portion thereof, and a pharmaceutically acceptable carrier. Such a vaccine has therapeutic and / or prophylactic benefit.

In another aspect, the invention provides a method of making a vaccine comprising a modified immunogenic H. pylori polypeptide, e.g. a surface or secretory polypeptide, or an active portion thereof, and a pharmacologically acceptable carrier.

In another aspect, the invention relates to a method of assessing the ability of a compound e.g. a polypeptide, e.g. a fragment of a host cell polypeptide, to bind the H. pylori polypeptide. The method comprises: contacting the test compound with an H. pylori polypeptide and determining whether the compound binds or otherwise interacts with the H. pylori polypeptide. Compounds that bind H. pylori are candidates as activators or inhibitors of the bacterial life cycle. These assays may be performed in vitro or in vivo.

In another aspect, the invention relates to a method of assessing the ability of a compound e.g. a polypeptide, e.g. a fragment of a host cell polypeptide, to bind H. pylori nucleic acid, e.g. DNA or RNA. The method comprises: contacting the test compound with an H. pylori nucleic acid and determining whether the compound binds or otherwise interacts with the H. pylori polypeptide. Compounds that bind H. pylori are candidates as activators or inhibitors of the bacterial life cycle. These assays may be performed in vitro or in vivo.

The invention relates to H. pylori polypeptides, preferably a substantially pure preparation of H. pylori polypeptide or recombinant H. pylori polypeptide. In preferred embodiments: the polypeptide has biological activity; the polypeptide has an amino acid sequence at least 60%, 70%, 80%, 90%, 95%, 98%, or 99% identical or homologous to the amino acid sequence of the invention contained in the Sequence Listing, preferably having approximately 65% sequence identity to the amino acid sequence of of the invention contained in the Sequence Listing, and most preferably has about 92% to 99% sequence identity to the amino acid sequence of the invention comprised in the Sequence Listing; the polypeptide has an amino acid sequence substantially the same as the amino acid sequence of the invention, which is contained in the Sequence Listing; the polypeptide is at least 5, 10, 20, 50, 100, or 150 amino acid residues in length; the polypeptide comprises at least 5, preferably at least 10, more preferably at least 20, more preferably at least 50, 100 or 150 contiguous amino acid residues of the invention that are included in the Sequence Listing. In yet another preferred embodiment, the invention comprises an amino acid sequence that differs in sequence identity of about 7% to about 8% from the H. pylori amino acid sequences of the invention that are contained in the Sequence Listing.

In preferred embodiments: the H. pylori polypeptide is encoded by a nucleic acid comprised in the Sequence Listing or by a nucleic acid having at least 60%, 70%, 80%, 90%, 95%, 98% or 99% homology to the nucleic acid of the invention contained in the sequence list.

In a preferred embodiment, the subject H. pylori polypeptide differs in amino acid sequence in 1, 2, 3, 5, 10, or more residues from a sequence of the invention that is included in the Sequence Listing. However, the differences are only such that the H. pylori polypeptide exhibits biological activity of H. pylori, e.g. the H. pylori polypeptide retains the biological activity of the naturally occurring H. pylori polypeptide.

In preferred embodiments, the polypeptide comprises all or fragments of the amino acid sequences of the invention that are contained in the Sequence Listing; fused in reading frame to another amino acid residue, preferably to a residue encoded by 5 'or 3' genomic DNA to genomic DNA that encodes a sequence of the invention contained in the Sequence Listing.

In yet other preferred embodiments, the H. pylori polypeptide is a recombinant fusion protein comprising a first portion of the H. pylori polypeptide and a second polypeptide portion, e.g. the second polypeptide portion has an amino acid sequence that does not refer to H. pylori. The second polypeptide moiety may be e.g. glutathione-S-transferase, DNA binding domain, or polymerase activating domain. In a preferred embodiment, the fusion protein may be used in a two-hybrid assay.

Polypeptides of the invention include those resulting from alternative transcription, alternative RNA splicing, and alternative translational and posttranslational events.

The invention also encompasses an immunogenic component comprising at least one H. pylori polypeptide in an immunogenic composition. The immunogenic component is capable of eliciting an immune response that is specific for an H. pylori polypeptide, e.g. a hormonal response, an antibody response, or a cellular response. In preferred embodiments, the immunogenic component comprises at least one antigenic determinant from a polypeptide of the invention that is included in the Sequence Listing.

In another aspect, the invention provides a substantially pure nucleic acid having a nucleotide sequence that encodes a H. pylori polypeptide. In preferred embodiments: the encoded polypeptide has biological activity; the encoded polypeptide has an amino acid sequence at least 60%, 70%, 80%, 90%, 95%, 98% or 99% homologous to the amino acid sequence of the invention contained in the Sequence Listing; the encoded polypeptide has an amino acid sequence substantially the same as the amino acid sequence of the invention, which is contained in the Sequence Listing; the encoded polypeptide is at least 5, 10, 20, 50, 100, or 150 amino acid residues in length; the encoded polypeptide comprises at least 5, preferably at least 10, more preferably at least 20, more preferably at least 50, 100 or 150 consecutive amino acid residues of the invention that are contained in the Sequence Listing.

In preferred embodiments: the nucleic acid of the invention is contained in the Sequence Listing; the nucleic acid has at least 60%, 70%, 80%, 90%, 95%, 98% or 99% homology to the nucleic acid of the invention contained in the Sequence Listing.

In a preferred embodiment, the encoded H. pylori polypeptide differs (e.g., by amino acid substitution, addition or deletion of at least one amino acid residue) in the amino acid sequence at 1, 2, 3, 5, 10, or more residues from the sequence of the invention that is contained in List the sequences. However, the differences are only such that: the polypeptide encoded by H. pylori exhibits biological activity of H. pylori, e.g. the enzyme encoded by H. pylori retains the biological activity of naturally occurring H. pylori.

In preferred embodiments, the encoded polypeptide comprises all or a fragment of the amino acid sequences of the invention that are contained in the Sequence Listing; fused in-frame to other amino acid residues, preferably residues encoded by genomic DNA 5 'or 3' to genomic DNA that encodes a sequence of the invention contained in the Sequence Listing.

In preferred embodiments, the subject H. pylori nucleic acid will comprise a transcriptional regulatory sequence, e.g. at least one transcriptional promoter or transcriptional enhancer operably linked to a H. pylori gene sequence, e.g. to adapt the H. pylori gene sequence to be suitable for expression in a recombinant host cell.

In yet another preferred embodiment, a nucleic acid that encodes a H. pylori polypeptide of the invention hybridizes under stringent conditions to a nucleic acid probe that corresponds to at least 8 consecutive nucleotides of the invention that are contained in the Sequence Listing; more preferably at least 12 contiguous nucleotides of the invention that are contained in the Sequence Listing; more preferably at least 20 contiguous nucleotides of the invention that are contained in the Sequence Listing; more preferably at least 40 contiguous nucleotides of the invention, which are included in the Sequence Listing.

In a preferred embodiment, the nucleic acid encodes a peptide that differs by at least one amino acid residue from the sequences of the invention that are contained in the Sequence Listing.

In a preferred embodiment, the nucleic acid differs by at least one nucleotide from the nucleotide sequences of the invention contained in the Sequence Listing.

In another aspect, the invention includes: a vector comprising a nucleic acid that encodes an H. pylori polypeptide or a H. pylori polypeptide variant as described herein; a vector transfected host cell; and a method of generating a recombinant H. pylori polypeptide or variant H. pylori polypeptide, including culturing a cell, e.g. in a cell culture medium, and isolating the H. pylori or H. pylori polypeptide variant e.g. from a cell or cell culture medium.

In another aspect, the invention relates to a purified recombinant nucleic acid having at least 50%, 60%, 70%, 80%, 90%, 95%, 98% or 99% homology to the sequence of the invention included in the Sequence Listing.

The invention also provides a probe or primer that comprises a substantially purified oligonucleotide. The oligonucleotide comprises a region of a nucleotide sequence that hybridizes under stringent conditions to at least 8 consecutive nucleotides of the sense or antisense sequence of the invention that is contained in the Sequence Listing, or naturally occurring mutants thereof. In preferred embodiments, the probe or primer further comprises an attached labeling moiety. The labeling group may be e.g. preferably an oligonucleotide is at least 8 and less than 10, 20, 30, 50, 100, or 150 nucleotides in length.

The invention also provides an isolated H. pylori polypeptide that is encoded by a nucleic acid that hybridizes under stringent conditions to the nucleic acid contained in the Sequence Listing.

The invention further provides nucleic acids, e.g. RNA or DNA encoding a polypeptide of the invention. These include double-stranded nucleic acids as well as coding and antisense single strands.

The H. pylori strain from which the genomic sequence was sequenced was deposited with the American Type Culture Collection (ATCC No. 55679; deposited by Genome Therapeutics Corporation, 100 Beaver Street, Waltham, MA 02154) as an HP-J99 strain.

Included in the invention; allelic variations; natural mutants; induced mutants; proteins encoded by DNA which hybridizes under very or low stringency conditions to a nucleic acid that encodes a polypeptide of the invention contained in the Sequence Listing (for definition of very and low stringency conditions, see Current Protocols in Molecular Biology, John Wiley & Sons, New York, 1989) , 6.3.1-6.3.6 and 6.4.1-6.4.10, herein incorporated by reference); and polypeptides that are specifically bound by antisera to H. pylori polypeptides, especially antisera to the active sites or binding domains of the H. pylori polypeptide. The invention also includes fragments, preferably biologically active fragments. These and other polypeptides are also referred to herein as H. pylori analogs or variants.

Table 1 lists possible functions that have been identified for several H. pylori polypeptides of the invention.

Further, the present invention includes H. pylori polypeptides characterized as shown in Table 1 below, inclusive; H. pylori cell envelope proteins, H. pylori secretory proteins, H. pylori cytoplasmic proteins, and H. pylori cellular proteins. Members of these groups were identified by BLAST homology searches and through secretion signal searches or transmembrane protein motifs. Polypeptides related to significant polypeptide homology in Table 1 are also considered to be classified in the same manner as the homologues listed in Table 1.

Table 1

NT sequ. no. [PCT] AK SEQ. no. [PCT] A. CELL PACKAGING A.1 Associated with flagella hp 1 p13939_24322162_f3_17 63 160 A.2 Outer membrane A.2.1 End Phe residue 02ge10116_23462_f2_43 7 104 02ge10116_804550_f2_44 8 105 02ge41622_14875000_c2_65 9 106 01cp20708_214843_c2_49 13 110 01cp20708_4960952_c1_43 14 111 06ae11016_4729625_c3_68 23 120 06ep10615_49068_c2_87 24 121 06gp71906_35158328_f3_85 27 124

06gp71906_3941642_f2_70 28 125 13ae10610_156411_c3_33 50 147 13ae10610_6522827_c3_37 51 148 hp4e53394_11798952_c2_101 61 158 06ge20501_4298568_c3_53 79 176 11ae12004_3367666_c2_41 80 177 hp7e10433_5345837_c3_13 84 181 14ce61516_24609816_f2_9 85 182 11ap20714_2077_c3_103 91 188 02cp10615_21908138_f1_4 94 191 A.2.2 No terminal Phe residue 07gp11909_26460892_f2_6 5 102 A.2.3 Phe and Tyr Cluster at the End 02ge41622_34176513_c1_50 11 108 06gp71906_20486556_f2_65 26 123 hp7e10520_14728137_f1_1 36 133 02ae31010_417818_f3_29 42 139 13ae10610_26855313_f3_15 52 149 A.2.4 Through homology hp5p15212_13729635_c3_35 22 119 07ee11402_1046877_c3_100 29 126 14ee41924_1046877_c3_104 30 127 hp1p13939_21641016_f1_1 65 162 hp4p62853_4766691_f3_23 66 163 A.3 Internal membrane A.3.1 Proteins involved in the transport

06cp30603_664083_c1_94 48 145 09cp10713_36359687_c1_119 49 146 04ep41903_16667055_c1_37 17 114 04ep41903_19689182_c1_43 18 115 14ce31519_24650009_c1_17 19 116 09ce10413_26734687_f3_23 43 140 hp6p10904_6726062_f3_13 44 141 A.3.2 Other inner membrane proteins 02ae31010_16679640_f2_21 38 135 07ee50709_16679640_f3_60 39 136 A.4 Other cell envelope proteins 01ce61016_1056562_c3_123 1 98 09cp61003_16619192_c2_83 2 99 02ge10116_15632000_c2_114 6 103 04ae61517_12345837J2_4 34 131 04ae61517_21744091_f3_5 35 132 hp4e13394_26750068_c3_113 60 157 hp5p15575_1053590_c1_35 69 166 hp7e10433_5345837_c2_8 83 180 B. CYTOPLASMATIC PROTEINS B.1. Proteins involved in mRNA translation hp3e10946_32609412_f3_4 57 154 hp3e10946_34175837_f3_3 58 155 B.2 Proteins involved in genomic replication, transcription, recombination, and repair

14CE-61516_12600937_f2_11 86 183 14cp11908_25402267_c3_104 87 184 B.3 Other cytoplasmic proteins 05ce10910_23712780_c1_4 88 185 hp7e10192_23712780_f2_5 89 186 11 ap20714_34663910_f3_29 92 189 hp8e10065_4962812_f2__18 93 190 C. ELIMINATED PROTEINS 01ce61016_23593955_c3_140 3 100 09cp61003_23593955_c1_79 4 101 02ge41622_20730462_f1_19 10 107 01cp20708_10628177_c2_50 12 109 05ae30220_24415693_c3_175 20 117 06gp10409_4015687_f2_11 25 122 hp2e10911_10213593_c1_73 31 128 hp2e10911_35567005_c2_88 32 129 09ze10333_1457137_f3_11 45 142 06cp30603_10744075_c3_136 46 143 12ae10622_30273255_f1_13 53 150 05ce10208_4707035_c2_17 64 161 06ep30223_176437_c2_134 67 164 hp5p15575_26016387_f2_16 70 167 hp6p12244_4881375_c3_97 77 174 06ce20610_34647187_c2_33 78 175 hp7e10433_36339535_f3_3 81 178 hp7e10433_36339535_f3_3 82 179 hp7e10420_24391078_f1_3 90 187 02ce71018_35720091_c3_4 95 192

hp6e10363_30517031_f3_3 97 194 D. OTHER CELL PROTEINS 01ae11010_26437877_c2_52 15 112 hp4p33322_5891077_c2_45 16 113 hp3p21118_54628_c3_3 21 118 02ae31010_1064125_f1_11 33 130 hp2e10911_15680337_c3_105 37 134 hp2e10911_24804577_c3_104 40 137 hp2e10911_32234750_c1_68 41 138 06cp30603_26070252_c3_140 47 144 03ae10804_235286_f3_19 54 151 09ge11604_4804692_c1_8 55 152 hp2p10610_21987687_c2_5 56 153 hp4e13394_26182793_f2_45 59 156 hp4e53394_2082126_c2_102 62 159 06ep30223_25402187_c1_112 68 165 hp6e10491_12712706_f3_12 71 168 hp6p12129_12542880_c3_29 72 169 hp6p12129_17067265_c3_29 73 170 hp6p12129_214055_f1_2 74 171 hp6p12129_214055_f3_17 75 172 hp6p12244_33492712_c3_88 76 173 hp1 e13054_22360653_f2_4 96 193

In Table 1, "NT" means the nucleotide sequence identification number and "AK" means the amino acid sequence identification number.

definitions

The terms "purified polypeptide" and "isolated polypeptide" and "substantially pure preparation of a polypeptide" are used interchangeably herein and mean without the other proteins, lipids, and nucleic acids with which they naturally occur. Preferably, the polypeptides are also separated from the substances, e.g. antibodies or gel matrix, e.g. polyacrylamide used for their purification. Preferably, the polypeptides represent at least 10, 20, 50, 70, 80, or 95% of the dry weight of the purified preparation. Preferably, the composition comprises: sufficient polypeptide to allow protein sequencing; at least 1, 10, or 100 µg of polypeptide; at least 1.10 or 100 mg of polypeptide. In addition, the terms "purified polypeptide and" isolated polypeptide "and" substantially pure preparation of a polypeptide "as used herein refer to both a polypeptide derived from naturally and a polypeptide produced by recombinant DNA techniques as described herein.

For example, an "isolated or" purified "protein or biologically active portion thereof is substantially free of cellular material or other contaminating proteins from a cell or tissue source from which the H. pylori protein is derived, or substantially free of chemical precursors or other chemicals, if chemically synthesized. The term "substantially free of cellular material" includes preparations of H. pylori protein in which the protein is separated from cellular components from cells from which it is isolated or recombinantly produced. In one embodiment, the term "substantially free of cell material" includes preparations of an H. pylori protein having less than about 30% (dry weight) of a protein other than H. pylori (also referred to herein as a "contaminating protein"), more preferably less than about 20%. more preferably less than about 10% of a non-H. pylori protein, and most preferably less than about 5% of a non-H. pylori protein. If the H. pylori protein or biologically active portion thereof is recombinantly produced, it is also preferably substantially free of culture medium, that is, the culture medium is less than about 20%, more preferably less than about 10% and most preferably less than about 5% by volume. protein preparation.

The term "substantially free of chemical precursors or other chemicals includes preparations of the H. pylori protein in which the protein is separated from chemical precursors or other chemicals that are involved in protein synthesis. In this embodiment, the term "substantially free of chemical precursors or other chemicals" includes preparations of an H. pylori protein having less than about 30% (dry weight) chemical precursors or other chemicals than H. pylori, more preferably less than about 20% chemical precursors or other chemicals such as H. pylori, even more preferably less than about 10% chemical precursors or other chemicals such as H. pylori, and most preferably less than about 5% chemical precursors or other chemicals such as H. pylori.

A purified cellular preparation means, in the case of plant or animal cells, an in vitro cellular preparation and not an entire plant or animal. In the case of cultured cells or microbial cells, it consists of a composition with at least 10% and more preferably 50% of the subject cells.

A purified or isolated or substantially pure nucleic acid, i.e. substantially pure DNA (the terms are used interchangeably herein), is a nucleic acid having one or both of the following characteristics: it is not directly linked to the two coding sequences to which it is directly linked (i.e. means one at the 5 'end and one at the 3' end) of the naturally occurring genome of the organism from which the nucleic acid is derived; or which is substantially free of the nucleic acid with which it occurs in the organism from which the nucleic acid was derived. The term includes, for example, recombinant DNA that is incorporated into a vector, e.g. into an autonomously replicating plasmid or virus, or into a genomic DNA of a prokaryote or eukaryote, or which exists as a separate molecule (e.g., a cDNA or genomic DNA fragment produced by PCR or by restriction endonuclease treatment) independently of other DNA sequences. Substantially pure DNA also includes recombinant DNA that is part of a hybrid gene encoding another H. pylori DNA sequence.

A "contig" as used herein is a nucleic acid that represents a continuous range of the genomic sequence of an organism.

An "open reading frame", also referred to herein as an ORF, is a region of a nucleic acid that encodes a polypeptide. This region may represent part of the coding sequence or the entire sequence and may be determined from the stop to the stop codon or from the start to the stop codon.

As used herein, a coding sequence is a nucleic acid that is transcribed into a messenger RNA and / or translated into a polypeptide when placed under the control of appropriate regulatory sequences. The boundaries of the coding sequence are determined by a translation start codon at the 5 'end and a translation stop codon at the 3' end. The coding sequence may include, but is not limited to, messenger RNA, synthetic DNA, and recombinant nucleic acid sequences.

A "complement" of a nucleic acid as used herein means an antiparallel or antisense sequence that corresponds to a Watson-Crick base pairing with the original sequence.

A "gene product" is a protein or structural RNA that is specifically encoded by a gene.

The term "probe," as used herein, means a nucleic acid, peptide, or other chemical entity that specifically binds to a target molecule. Probes are often connected or able to associate with the label. The label is the chemical part that can be detected. Typical labels include dyes, radioisotopes, luminescent and chemiluminescent moieties, fluorophores, enzymes, precipitating agents, amplification sequences, and the like. Similarly, nucleic acids, peptides, or other chemical entities that specifically bind a target molecule and immobilize such a molecule are referred to herein as "scavenger ligands." The capture ligands are typically bonded or capable of bonding to a support such as nitrocellulose, glass, nylon membranes, beads, particles, and the like. The specificity of the hybridization is dependent upon conditions such as the composition of the base pair of nucleotides and the temperature and concentration of salts in the reaction mixture. These conditions are routinely determined by one skilled in the art by routine experimentation.

Homology refers to sequence similarity or sequence identity between two polypeptides or between two nucleic acid molecules. If the same base or amino acid monomeric subunit is located at a certain position in both of the two sequences being compared, e.g. if adenine is placed at a certain position in each of the two DNA molecules, then the molecule is homologous at that position. The percent homology between two sequences is a function of the number of identical or homologous positions shared by the two sequences divided by the number of aligned positions x 100. For example, if 6 of the 10 positions in the two sequences are identical or homologous, then the two sequences are 60% homologous. For example, the DNA sequences ATTGCC and TATGGC share 50% homology. Generally, comparisons are performed when the two sequences are aligned to have maximum homology.

Nucleic acids are capable of hybridizing with each other when at least one strand of nucleic acid can anneal to another nucleic acid under defined stringent conditions. The stringency of the hybridization is determined; (a) the temperature at which the hybridization and / or wash is performed; and b) the ionic strength and polarity of the hybridization and wash solutions. Hybridization requires that two nucleic acids contain complementary sequences; however, depending on the stringency of the hybridization, some mismatches may be tolerated. Typically, hybridization of two sequences at high stringency (e.g., in a 0.5 x SSC solution at 65 ° C) requires that the sequences are substantially completely homologous. Under conditions of moderate stringency (such as 2 x SSC at 65 ° C) and low stringency (such as 2 x SSC at 55 ° C), a correspondingly lower overall complementarity between hybridizing sequences is required. (1 x SSC is 0.15 M NaCl, 0.015 M Na citrate). A preferred, non-limiting example of stringent hybridization conditions is hybridization in 6 x sodium chloride / sodium citrate (SSC) at about 45 ° C, followed by one or more washes in 0.2 x SSC, 0.1% SDS at 50 to 65 ° C .

The terms peptides, proteins and polypeplides are used interchangeably herein.

The term "surface protein" as used herein means all surface-accessible proteins, e.g. inner and outer membrane proteins, cell wall adhering proteins, and secretory proteins.

A polypeptide has the biological activity of H. pylori if it has one, two or preferably more of the following properties: (1) when expressed in the case of H. pylori infection, it can provide or mediate the attachment of H. pylori to the cell; (2) has an enzymatic activity, structural or regulatory function characteristic of the H. pylori protein, (3) the gene encoding it can cure a lethal mutation in the H. pylori gene, (4) or is immunogenic in the subject. A polypeptide has biological activity when it is an antagonist, agonist or super agonist of a polypeptide having one of the above properties.

The biologically active fragment or analog has in vivo or in vitro activity characteristic of the H. pylori polypeptides of the invention contained in the Sequence Listing or other naturally occurring H. pylori polypeptides, e.g. one or more biological activities described herein. Particularly preferred are fragments that exist in vivo, e.g. fragments that arise from post-transcriptional processing, or that result from the translation of alternatively spliced RNA. Fragments include those that are expressed in natural or endogenous cells, as well as those produced in expression systems, e.g. CHO cells. Because proteins such as H. pylori polypeptides often exhibit different physiological properties, and because such properties can be attributed to different parts of the molecule, a useful H. pylori fragment or H. pylori analog is one that exhibits biological activity in any H. pylori biological assay. . Most preferably, the fragment or analog has 10%, preferably 40%, more preferably 60%, 70%, 80% or 90% or greater H. pylori activity, in vivo or in vitro assays.

Analogs may differ from naturally occurring H. pylori polypeptides in an amino acid sequence or in a non-sequence manner, or both. Non-sequential modifications include changes in acetylation, methylation, phosphorylation, carboxylation, or glycosylation. Preferred analogs include H. pylori polypeptides (or active fragments thereof) whose sequences differ from naturally occurring sequences by one or more conservative amino acid substitutions or one or more non-conservative amino acid substitutions, deletions, or insertions that do not substantially reduce the biological activity of the H. polypeptide. pylori. Conservative substitutions typically include substitution of one amino acid with another with similar properties, e.g. substitutions within the following groups: valine, glycine; glycine, alanine; valine, isoleucine, leucine; aspartic acid, glutamic acid; asparagine, glutamine; serine, threonine; lysine, arginine; and phenylalanine, tyrosine. Other conservative substitutions may be made according to the table below.

Table 2

Conservative amino acid substitutions

For the amino acid code Replacement for any of alanine A D-Ala, Gly, beta-Ala, L-Cys, and D-Cys arginine R D-Arg, Lys, D-Lys, homo-Arg, D-homo-Arg, Met, Ile, D-Met, D-Ile, Orn, D-Orn asparagine N D-Asn, Asp, D-Asp, Glu, D-Glu, Gln, D-Gln acid aspartic D D-Asp, D-Asn, Asn, Glu, D-Glu, Gln, D-Gln cysteine C D-Cys, S-Me-Cys, Met, D-Met, Thr, D-Thr glutamine Q D-Gln, Asn, D-Asn, Glu, D-Glu, Asp, D-Asp acid glutamic E D-Glu, D-Asp, Asp, Asn, D-Asn, Gln, D-Gln glycine G Ala, D-Ala, Pro, D-Pro, beta-Ala, Acp isoleucine I D-Ile, Val, D-Val, Leu, D-Leu, Met, D-Met leucine L D-Leu, D-Val, D-Val, Leu, D-Leu, Met, D-Met lysine The D-Lys, Arg, D-Arg, Homo-Arg, D-Homo-Arg, Met, D-Met, Ile, D-Ile, Orn, D-Om methionine M D-Met, S-Me-Cys, Le, D-Le, Val, DVal phenylalanine F D-Phe, Tyr, D-Thr, L-Dopa, His, D-His, Trp, DTrp, Trans-3,4, or 5-phenylproline, cis-3,4, or 5-phenylproline proline P D-Pro, L-1-thioazolidine-4-carboxylic acid, or L-1-oxazolidine-4-carboxylic acid

For the amino acid code Replacement for any of serine WITH D-Ser, Thr, D-Thr, allo-Thr, Met, D-Met, Met (O), D-Met (O), L-Cys, and D-Cys threonine T D-Thr, Ser, D-Ser, allo-Thr, Met, D-Met, Met (O), D-Met (O), Val, D-Val tyrosine Y D-Tyr, Phe, D-Phe, L-Dopa, His, D-His valine in D-Val, Leu, D-Leu, lle, D-lle, Met, D-Met

Other analogs of the invention are those containing modifications that enhance the stability of the peptide; such analogs may contain, for example, one or more non-peptide bonds (which replace peptide bonds) in the peptide sequence. Also included are: analogs that contain residues other than naturally occurring L-amino acids, e.g., D-amino acids or non-naturally occurring or synthetic amino acids, e.g. β or γ amino acids; and cyclic analogs.

The term "fragment" as used herein for an H. pylori analogue will typically be at least about 20 residues in length, more typically at least about 40 residues, preferably at least about 60 residues. H. pylori polypeptide fragments can be generated by methods known to those skilled in the art. Also included are H. pylori polypeptides containing residues that are not necessary for the biological activity of the peptide, or that result from alternative splicing of mRNA or from alternative protein processing procedures.

An "immunogenic component" as used herein is an entity such as a H. pylori polypeptide, analog, or fragment that is capable of eliciting a humoral and / or cellular immune response of a host animal, either alone or with an adjuvant.

An "antigenic component" as used herein is an entity, such as a H. pylori polypeptide, analog, or fragment, that is capable of binding to a specific antibody with sufficiently high affinity to form a detectable antigen-antibody complex.

The term "transgene," as used herein, means a nucleic acid (encoding, for example, one or more polypeptides) that is in part or all heterologous, i.e. foreign, to a transgenic animal or cell into which it is incorporated, but which is designed to be incorporated into, or incorporated into, the cellular genome in such a way that it alters the genome of the cell into which it has been incorporated (e.g., is inserted into a position that differs from, or results in, the deletion of the gene). The transgene may comprise one or more transcriptional regulatory sequences and any other nucleic acid, such as introns, that may be necessary for optimal expression of the selected nucleic acid, all of which are operably linked to the selected nucleic acid, and may include an enhancer sequence.

The term "transgenic cell" as used herein means a cell containing the transgene.

A "transgenic animal" as used herein is any animal in which one or more, and preferably substantially all, cells contain a transgene. The transgene may be incorporated into the cell directly or indirectly by incorporation into a cell precursor by a method of relaxed genetic manipulation, such as by transformation of competent cells, or by micro-infection or infection with a recombinant virus. This molecule may be integrated inside the chromosome, or may be extrachromosomally replicating DNA.

The term "antibody" as used herein is intended to include fragments thereof that specifically react with H. pylori polypeptides.

As used herein, the term "cell-specific promoter" means a DNA sequence that serves as a promoter, that is, it regulates the expression of a selected DNA sequence that is operably linked to a promoter and that affects the expression of the selected DNA sequence in specific cells or tissue. . The term also covers so-called "leakage promoters, which primarily regulate expression of the selected DNA in one tissue, but also trigger expression in other tissues.

"Misexpression" as used herein means an unnatural type of gene expression method. Includes: expression at unnatural type levels; overexpressing; an expression method that differs from the wild type in terms of time or stage at which the gene is expressed, e.g. increasing or decreasing expression (as compared to wild type) at a predetermined developmental period or stage; an expression method that differs from wild type in terms of reduced expression (as compared to wild type) in a predetermined cell or tissue type; an expression method that differs from the wild type in terms of spliced size, amino acid sequence, post-restriction modifications, or biological activity of the expressed protein; an expression method that differs from the wild type in terms of the effect of environmental or extracellular stimuli on gene expression, e.g. a method of increasing or decreasing expression (as compared to wild type) in increasing or decreasing the stimulus potency.

The term "host cells as used herein and other such terms" refers to microorganisms or lines of higher eukaryotic cells cultured as unicellular entities, and means cells that can become or can be used as recipients of a recombinant vector or other transferred DNA, and include the progeny of the original cell that has been transfected. It will be appreciated by those skilled in the art that the progeny of a single parent cell need not necessarily be completely identical in genome or total DNA content to the parent, due to a random or targeted mutation.

The term "control sequence" as used herein means a nucleotide sequence with a base sequence that is recognized by the host organism so as to affect the expression of the coding sequence with which it is ligated. The nature of such a control sequence varies depending on the host organism; in prokaryotes, such a control sequence generally includes a promoter, a ribosome binding site, terminators, and in some cases enhancers. The term control sequence is intended to include at least all components whose presence is necessary for expression, and may also include other components whose presence is preferred, e.g. leader sequences.

The term "operably linked," as used herein, means combining or ligating sequences to function as intended. For example, a control sequence is operably linked to a coding sequence in such a way as to achieve expression of the coding sequence under conditions compatible with the control sequence and the host cell.

"Metabolism of a substance as used herein means any aspect of the expression, function, activity or regulation of a substance. The metabolism of the agent includes modifications, e.g. covalent or non-covalent modifications of the substance. The metabolism of the agent includes modifications, e.g. covalent or non-covalent modifications that the substance induces in other substances. The metabolism of a substance also involves changes in the distribution of the substance. The metabolism of a substance also includes changes that the substance induces in the distribution of other substances.

The term "sample as used herein" means a biological sample, such as tissue or fluid isolated from an individual (including, without limitation, plasma, serum, cerebrospinal fluid, lymph, tears, saliva and tissue sections) or from in vitro cell cultures. as well as environmental samples.

Embodiments of the invention will employ, unless otherwise indicated, conventional techniques of chemistry, molecular biology, microbiology, recombinant DNA, and immunology known in the art. Such techniques are fully explained in the literature. See e.g. Sambrook, Fritsch, and Maniatis, Molecular Cloning; Laboratory Manual 2nd ed. (1989); DNA Cloning, Volume I and II (D. N Glover ed. 1985); Oligonucleotide Synthesis (M.J. Gait ed., 1984); Nucleic Acid Hybridization (B. D. Hames & S. J. Higgins ed. 1984); series, Methods in Enzymology (Academic Press, Inc.), especially Vol. 154 and Vol. 155 (Wu and Grossman, Ed.) And PCR-A Practical Approach (McPherson, Quirke, and Taylor, Ed., 1991).

I. Isolation of N-Acids from H. pylori and Use thereof

The genomic sequence of H. pylori

The present invention provides nucleotide sequences of the H. pylori genome, and thus includes a DNA sequence library of H. pylori genomic DNA. The detailed description that follows provides the nucleotide sequence of H. pylori and also describes how this sequence was obtained and how the ORF and protein coding sequences were identified. Also described are methods of using the claimed H. pylori sequences, including diagnostic and therapeutic applications. In addition, the library can be used as a database to identify and compare medically important sequences in this and other H. pylori strains.

To determine the genomic sequence of H. pylori, DNA from H. pylori strain (ATCC No. 55679; deposited with Genome Therapeutics Corporation, 100 Beaver Street, Waitham, MA 02154) was isolated and mechanically cut by nebulization to a medium size of 2 kb. After size fractionation by gel electrophoresis, the fragments were blunt, adapter nucleotides ligated, and the fragments were cloned into each of 20 different pMPX vectors (Rice et al., Abstracts of Meeting of Genome Mapping and Sequencing, Cold Spring Harbor, NY, 5/11). -5/15, 1994, p. 225) to construct a series of shotgun subclone libraries.

DNA sequencing was achieved using multiplex sequencing procedures, essentially as described in Church et al., 1988, Science 240: 185: U.S. Pat. U.S. Pat. 4,942,124 and 5,149,625). The DNA was extracted from the harvested cultures and sequenced chemically or enzymatically. The sequencing reaction mixtures were redissolved by electrophoresis and the products were transferred and covalently bound to nylon membranes. Finally, the membranes were sequentially hybridized with a series of labeled oligonucleotides complementary to the "tag" sequences that were in different shotgun cloning vectors. In this way, a large number of sequences could be obtained from one set of sequential reaction mixtures. Cloning and sequencing procedures are described in more detail in the examples.

Individual sequence records obtained in this manner were compiled using FALCON ™ (Church et al., 1994, Automated DNA Sequencing and Analysis, JC Venter, eds., Academic Press) and PHRAP (P. Green, Abstracts of DOE Human Genome Program Contractor- Grantee Workshop V, Jan. 1996, p. 157). The average length of the contig was approximately 3-4 kb.

Various approaches were used to obtain contigs containing a continuous sequence representing the entire H. pylori genome. Synthetic oligonucleotides are designed to be complementary to sequences at the end of each contig. In order to identify clones that contain linking regions between individual contigs, these oligonucleotides can be hybridized to a H. pylori genomic DNA library, for example, in lambda phage vectors or plasmid vectors. Such clones are then used to isolate the tempiate DNA and the same oligonucleotides are then used as primers in the polymerase chain reaction (PCR) to amplify the linker fragments, and then the nucleotide sequence of these fragments is determined.

H. pylori sequences were analyzed for the presence of open reading frames (ORFs) of at least 180 nucleotides. It should be understood that the result of the ORF analysis based on stop-stop codon readings may not correspond to the ORF of the naturally occurring H. pylori polypeptide. These ORFs may contain start codons that indicate the initiation of protein synthesis of a naturally occurring H. pylori polypeptide. Such a start codon within an ORF provided herein can be identified by one of ordinary skill in the relevant art, and the resulting ORF and encoded H. pylori polypeptide are within the scope of the invention. For example, within the ORF, codons AUG or GUG (encoding methionine or valine) that are part of the initiation signal for protein synthesis can be identified, and the ORF can be modified to the corresponding naturally occurring H. pylori polypeptide. The putative coding regions were defined by evaluating the coding potential of such sequences by the GENEMARK ™ program (Borodovsky and McLinnch, 1993, Comp. Chem. 17: 123).

Other H. pylori nucleic acids

The nucleic acids of the invention can be obtained directly from the DNA of the above-mentioned H. pylori strain using a polymerase chain reaction (PCR). See "PCR, A Practical Approach" (McPherson, Quirke, and Taylor, eds., IRL Press, Oxford, UK, 1991) for a more detailed description of PCR. High precision PCR can be used to ensure the identity of a copy of DNA prior to expression. In addition, the authenticity of the amplified products can be checked by conventional sequencing methods. The clones carrying the desired sequences described herein can also be obtained by screening libraries by PCR or by hybridizing synthetic oligonucleotide probes to filter lifts of library colonies or plaques, as known in the art (see, e.g., Sambrook et al., Molecular Cloning, A). Laboratory Manual 2nd Edition, 1989, Cold Spring Harbor Press, NY).

Also, according to the protocols described herein, nucleic acids encoding H. pylori polypeptides can be obtained from a cDNA library. The cDNA encoding the H. pylori polypeptide can be obtained by isolating total mRNA from the respective strain. Double-stranded cDNAs can then be prepared from total mRNA. Subsequently, the cDNAs can be incorporated into a suitable plasmid or viral (e.g., bacteriophage) vector using any of a variety of known techniques. Genes encoding H. pylori polypeptides can also be cloned using established polymerase chain reaction techniques in accordance with the nucleotide sequence information of the invention. The nucleic acids of the invention may be DNA or RNA. Preferred nucleic acids of the invention are listed in the Sequence Listing.

The nucleic acids of the invention can also be chemically synthesized using standard techniques. Various methods of chemical synthesis of polydeoxynucleotides are known, including solid phase synthesis, which, like peptide synthesis, is fully automated in commercially available DNA synthesizers (see, e.g., Itakura et al., U.S. Patent No. 4,598,049; Caruthers et al. No. 4,458,066 and US Patent Nos. 4,401,796 and 4,373,071, incorporated herein by reference).

Nucleic acids isolated or synthesized according to features of the present invention are useful, for example, without limitation, as probes, primers, capture ligands, antisense genes, and for the development of expression systems for the synthesis of proteins and peptides corresponding to these sequences. As probes, primers, capture ligands, and antisense agents, nucleic acids normally consist of all or part (about twenty or more nucleotides to provide specificity as well as the ability to form stable hybridization products) of the nucleic acids of the invention that are contained in the Sequence Listing. These uses are described in more detail below.

probes

A nucleic acid isolated or synthesized in accordance with the sequence of the invention, which is listed in the Sequence Listing, can be used as a probe for the specific detection of H. pylori. The sequence information in this application identifies sequences of twenty or more nucleotides that provide the desired inclusiveness and exclusivity with respect to H. pylori and foreign nucleic acids that may occur under hybridization conditions. More preferably, the sequence will contain at least twenty to thirty nucleotides to ensure the stability of the hybridization product formed between the probe and the intended target molecules.

It is difficult to synthesize sequences longer than 1000 nucleotides, but these can be generated by recombinant DNA techniques. Those skilled in the art will readily appreciate that nucleic acids for use as probes may be labeled to facilitate detection of the hybridization product.

A nucleic acid isolated or synthesized in accordance with the sequence of the invention, which is included in the Sequence Listing, can also be used as a probe to detect the homologous regions (especially homologous genes) of other Helicobacter strains using suitable stringent hybridization conditions as described herein.

Capture ligand

When used as a capture ligand, the nucleic acid selected in the above manner for probes can be routinely associated with the support. The method by which a nucleic acid is linked to substrates is well known. A nucleic acid comprising twenty or more nucleotides in a sequence of the invention, which is included in the Sequence Listing, can be used to separate H. pylori nucleic acid from another nucleic acid of the same and other organisms. A nucleic acid comprising twenty or more nucleotides in a sequence of the invention, which is included in the Sequence Listing, can also be used to separate Helicobacter species from each other and to separate them from other organisms. Preferably, the sequence will contain at least twenty nucleotides to ensure the stability of the hybridization product formed between the probe and the intended target molecules. It is difficult to synthesize sequences longer than 1000 nucleotides, but these can be generated by recombinant DNA techniques.

primers

A nucleic acid isolated or synthesized in accordance with the sequence of the invention, which is listed in the Sequence Listing, can be used as a primer to amplify H. pylon nucleic acid. These nucleic acids can also be used as primers to amplify nucleic acids in other Helicobacter species. Due to the polymerase chain reaction (PCR) techniques, a nucleic acid sequence of 10-15 nucleotides of the invention contained in the Sequence Listing can be used together with suitable enzymes and reagents to make copies of H. pylori nucleic acid. More preferably, the sequence will contain at least twenty or more nucleotides to ensure the stability of the hybridization product formed between the primer and the intended target molecules. It is difficult to control the binding conditions of primers longer than 100 nucleotides and to achieve specificity using them. High-precision PCR can be used to ensure the identity of the DNA copy prior to expression. In addition, the amplified products can be checked by conventional sequencing methods.

The copies may be used in diagnostic assays to detect specific sequences, including genes from H. pylori and / or other Helicobacter species. The copies may also be incorporated into cloning and expression vectors to generate polypeptides corresponding to the nucleic acid synthesized by PCR, as described in more detail herein.

antisense

Nucleic acid or nucleic acid hybridizing derivatives isolated or synthesized in accordance with the sequence described herein can be used as antisense agents to prevent expression of H. pylori genes. These sequences can also be used as antisense agents to prevent the expression of genes of other Helicobacter species.

In one embodiment, the nucleic acids or derivatives corresponding to H. pylori nucleic acids are loaded into a suitable carrier, such as a liposome or bacteriophage, for incorporation into bacterial cells. For example, a nucleic acid of twenty or more nucleotides is capable of binding to a bacterial nucleic acid or a mediator RNA. Preferably, the antisense nucleic acid comprises 20 or more nucleotides to provide the necessary stability of the hybridization product of the non-naturally occurring nucleic acid and bacterial nucleic acid and / or mediator RNA. It is difficult to synthesize sequences longer than 1000 nucleotides, but these can be generated by recombinant DNA techniques. Methods of loading nucleic acid into liposomes are known in the art, and U.S. Pat. No. 4,241,046, issued December 23, 1980 to Papahadjopoulos et al.

II. Expression of H. pylori nucleic acids

A nucleic acid that is isolated or synthesized in accordance with the sequences described herein can be used to generate polypeptides. The nucleic acid of the invention, exemplified in the Sequence Listing, or fragments thereof that encode active portions of H. pylori polypeptides may be cloned into suitable vectors or used to isolate the nucleic acid. The isolated nucleic acid is combined with appropriate DNA linkers and cloned into a suitable vector.

By expression in a bacterial strain, under conditions in which the activity of the gene products determined by the gene or operon under test can be specifically measured, the function of a particular gene or operon can be specified. Alternatively, a large amount of gene product can be generated in the expression strain for use as an antigen, as an industrial reactant, for structural studies and the like. This expression can be carried out in a mutant strain in which the gene to be tested is not active or in a strain that does not produce the same gene product. This includes, but is not limited to, other Helicobacter strains or other bacterial strains, such as E. coli, Norcardia, Corynebacterium, Campylobacter, and Streptomyces. In some cases, the expression host will utilize the native Helicobacter promoter, while in others it will be necessary to direct the gene with a promoter sequence derived from the expressing organism (e.g., the E. coli β-galactosidase promoter for expression in E. coli).

For example, the following procedure may be used to express a gene product utilizing the native H. pylori promoter. The restriction fragment containing the gene of interest, together with its associated natural promoter element and regulatory sequences (identified by DNA sequence data), is cloned into a suitable recombinant plasmid that contains an origin of replication that functions in the host organism and an appropriate selection marker. This can be accomplished by a number of methods known to those skilled in the art. Most preferably, the embodiment is by cleaving the plasmid and the fragment to be cloned with the same restriction endonuclease to create compatible ends that can be ligated, thereby joining the two pieces together. For example, the recombinant plasmid is incorporated into the host organism by electroporation, and cells containing the recombinant plasmid are identified by selection for a marker in the plasmid. Expression of the desired gene product is detected using gene product specific assays.

If it requires a different promoter, the gene body (coding sequence) is specifically excised and cloned into the appropriate expression plasmid. This subcloning can be accomplished in several ways, but the simplest is by PCT amplification of a specific fragment that, after treatment with a restriction enzyme or exonuclease PCR product, to form suitable ends for cloning, is ligated into an expression plasmid.

A suitable host cell for expression of the gene may be any prokaryotic or eukaryotic cell. For example, the H. pylori polypeptide may be expressed in bacterial cells such as E. coli, insect cells (baculovirus), yeast, or mammalian cells, such as Chinese hamster ovary (CHO) cells. Other suitable host cells are known to those skilled in the art.

Expression in eukaryotic cells, such as mammalian, yeast or insect cells, may result in partial or complete glycosylation and / or the formation of relevant inter- or intra-chain disulfide bonds in the recombinant peptide product. Examples of vectors for expression in yeast S. cerívisae include pYepSed (Baldari. Et al., (1987) Embo J. 6: 229234), pMFα (Kurjan and Herskowitz, (1982) Cell 30: 933-943), pJEY88 (Schultz et al. al., (1987) Gene 54: 113-123) and pYES2 (Invitrogen Corporation, San Diego, CA). Baculovirus vectors available for protein expression in cultured insect cells (SF 9 cells) include the pAc series (Smith et al., (1983) Mol. Cell Biol. 3: 2156-2165) and the pVL series (Lucklow, VA, and Summers, MD. , (1989) Virology 170: 31-39). In general, COS cells (Gluzman, Y. (1981) Cell 23: 175-182) are used in conjunction with such vectors as pCDM 8 (Aruffo, A and Seed, B., (1987) Proc. Natl. Acad. Sci.). USA 84: 8573-8577) for short-term amplification / expression in mammalian cells, while CHO cells (dhfr Chinese Hamster Ovary) are used with vectors such as pMT2PC (Kaufman et al. (1987), EMBO J. 6: 187 -195), for stable amplification / expression in mammalian cells. The DNA vector may be incorporated into mammalian cells by conventional techniques such as co-precipitation with calcium phosphate or calcium chloride, DEAE-dextran mediated transfection or electroporation. Suitable methods for transforming host cells can be found in Sambrook et. al. (Molecuiar Cloninq: A Laborator's Manual, second edition, Cold Spring Harbor Laboratory press (1989)), and other laboratory textbooks.

Expression in prokaryotes is most often performed in E. coli with either fused or non-fused inducible expression vectors. Fused vectors usually add several NH ₂ terminal amino acids to the expressed target gene. These NH ₂ terminal amino acids are often referred to as a reporter group. Typically, such reporter groups serve two purposes: 1) enhancing the solubility of the target recombinant protein; and 2) help purify the target recombinant protein by acting as a ligand in affinity purification. Often, a protoolytic cleavage site is incorporated into the fused expression vectors to link the reporter group and the target recombinant protein, allowing separation of the target recombinant protein from the reporter group following purification of the fusion protein. Such enzymes and their related recognition sequences include Factor Xa, thrombin and enterokinase. Typical fusion expression vectors include pGEX (Amrad Corp., Melbourne, Australia), pMAL (New England Biolabs, Beverly, MA) and pRIT5 (Pharmacia, Piscataway, NJ) that fuse glutathione-S-transferase, protein-binding maltose E, respectively. protein A, to the target recombinant protein. A preferred reporter group is poly (His), which can be fused to the carboxy terminus of the protein, and which makes the recombinant fusion protein readily purified by metal chelate chromatography.

Inducible unfused expression vectors include pTrc (Amann et al., (1988) Gene 69: 301-315) and pET11d (Studier et al., Gene Expression Technology: Methods in Enzymology 185. Academic Press, San Diego, California (1990) 60 -89). While in pTrc the expression of the target gene depends on transcription by the host RNA polymerase from the hybrid trp-lac fusion promoter, the expression of the target genes incorporated into pET11d depends on the transcription of the t7 gn10-lac 0 fusion promoter which is mediated by coexpressed viral RNA polymerase. This viral polymerase is supplied by the host strains BL21 (DE3) or HMS174 (DE3) from a λ prophase living therein that carries T7 gnl under transcriptional control of the laclIV 5 promoter.

For example, a host cell transfected with a nucleic acid vector that is intended to express a nucleic acid sequence encoding a H. pylori polypeptide may be cultured under appropriate conditions that allow expression of the polypeptide. The polypeptide may be secreted and isolated from a mixture of cells and peptide-containing medium. Alternatively, the polypeptide may be held in the cytoplasm, and then the cells are harvested, lysed, and the polypeptide isolated. Cell culture includes host cells, medium and other by-products. Suitable cell culture media are known in the art. Polypeptides of the invention can be isolated from cell culture medium, host cells, or both, using art-known protein purification techniques, including ion-exchange chromatography, goal filtration chromatography, ultrafiltration, electrophoresis, and immunoaffinity purification with antibodies specific for such polypeptides. In addition, in many situations, polypeptides can be produced by chemical cleavage of a native protein (e.g., by triptic cleavage), and the cleavage products can then be purified by standard techniques.

In the case of membrane-bound proteins, these can be isolated from the host cell by contacting a fraction of the membrane-associated protein and the detergent to form a solubilized complex where the membrane-associated protein is no longer incorporated into the membrane fraction and is dissolved at least to the extent that it can be chromatographically isolated from the membrane fraction. Several different criteria are used to select a detergent that is suitable for solubilizing these complexes. For example, one feature considered is the ability of the detergent to dissolve the H. pylori protein within the membrane fraction with minimal denaturation of the membrane-associated protein, so as to allow the activity or functionality of the membrane-associated protein to reconstitute. Another feature that is considered in the choice of detergent is the critical micellar concentration (CMC) of the detergent, wherein the selected detergent preferably has a higher CMC value that allows easy removal after reconstitution. A third property taken into consideration in the choice of detergent is the hydrophobicity of the detergent. Typically, membrane-associated proteins are very hydrophobic, so detergents that are also hydrophobic, e.g. tritone series would be useful for dissolving hydrophobic proteins. Another property important for the detergent may be the ability of the detergent to remove H. pylori protein with minimal protein-protein interaction, which facilitates further purification. Another feature of the detergent that should be taken into account is the detergent charge. For example, if it is desired to use ion exchange resins in the purification process, then the preferred detergent should not have a charge. Chromatographic techniques that can be used in the final purification step are known in the art and include hydrophobic interaction, lectin affinity, ion exchange, dye affinity, and immunoaffinity.

One strategy to maximize expression of recombinant H. pylori peptide in E. coli is to express the protein in a host bacterium with impaired ability to proteolytically cleave the recombinant protein (Gottesman, S., Gene

Expression Technology: Methods in Enzymology 185. Academic Press, San Diego, California (1990) 119-128. Another strategy could be to change the nucleic acid encoding the H. pylori peptide to be incorporated into the expression vector such that the individual codons of each amino acid would be those that are preferably used in highly expressed E. coli proteins (Wada et al., ( 1992) Nuc Acids Res 20: 2111-2118). Such a change of nucleic acids of the invention may be accomplished by standard DNA synthesis techniques.

The nucleic acids of the invention can also be chemically synthesized using standard techniques. Various methods of chemical synthesis of polydeoxynucleotides are known, including solid phase synthesis, which, like peptide synthesis, can be fully automated in commercially available DNA synthesizers (see, e.g., Itakura et al., US Patent No. 4,598,049; Caruthers et al. U.S. Patent No. 4,458,066 and Itakura U.S. Patent Nos. 4,401,796 and 4,373,071, which are incorporated herein by reference).

III. H. pylori polypeptides

The present invention encompasses isolated H. pylori polypeptides encoded by the claimed H. pylori genomic sequences, including polypeptides of the invention that are included in the Sequence Listing. The polypeptides of the invention preferably have a length of at least 5 amino acids. The use of the DNA sequence information provided herein for the amino acid sequences of the polypeptides of the invention can be derived by methods known in the art. It is to be understood that the entire nucleic acid sequence encoding H. pylori polypeptides can be isolated and identified based on an ORF that encodes only a fragment of the related, protein coding region. This can be achieved, for example, by using an isolated nucleic acid encoding an ORF or fragments thereof, to initiate a polymerase chain reaction with a genomic H. pylori nucleic acid as a template; followed by sequencing the amplified product.

Polypeptides of the invention may be isolated from the wild-type or mutant H. pylori cells or from heterologous organisms or cells (including but not limited to bacterial, yeast, insect, plant and mammalian cells) into which it has been incorporated and in which it has been expressed. H. pylori nucleic acid. In addition, the polypeptides may be part of a recombinant fusion protein.

The H. pylori polypeptides of the invention can be chemically synthesized using commercially automated procedures, for example those mentioned above.

H. pylori polypeptides of the invention also include chimeric proteins and truncated proteins as described.

Chimeric proteins of H. pylori

H. pylori chimeric proteins comprise one or more H. pylori polypeptides fused to each other. These combined sequences may be prepared by combining two or more genes, or two or more polypeptide coding sequences, or at least one gene and at least one polypeptide coding sequence in tandem, followed by expression of the encoded proteins by conventional molecular biology techniques. The linked nucleotide sequences may consist of a combination of either full-length H. pylori nucleotide sequences or fragments of such sequences, e.g. fragments that contain immunologically relevant portions of the encoded H. pylori protein. These H. pylori chimeric proteins then contain the combined or synergistic vaccine potential for each individual H. pylori protein sequence and can be used in the vaccine formulation of the invention.

Truncated gene expression and protein production

H. pylori proteins encoded by a given nucleotide sequence can also be used in a biologically active truncated form. Such truncation can be achieved, for example, by eliminating regions of the 5 'and / or 3' coding sequence of nucleotides. These truncations can affect recombinant expression of the encoded protein and / or subsequent purification of the protein. For example, truncation of the nucleotide sequence encoding the predicted export sequence of a specific protein may alter the expression of the protein. Alternatively, truncation of the C-terminus of a H. pylori polypeptide by eliminating the 3 'end of the nucleic acid coding region can also improve protein expression and subsequent purification and use, as indicated in Example VIII below. Deletion of the nucleic acid regions encoding the internal H. pylori protein may also result in improved expression, purification and / or efficacy of the protein as a vaccine candidate.

IV. Identification of nucleic acids that encode vaccine components and targets for agents effective against H. pylori

The claimed H. pylori genomic sequence includes segments that direct synthesis of carbon-nucleic acids and polypeptides, as well as origins of replication, promoters, other types of regulatory sequences, and inter-gene nucleic acids. The invention includes nucleic acids encoding immunogenic vaccine components and targets for agents effective against H. pylori. The identification of said immunogenic components involved in determining the function of the claimed sequences can be achieved using various approaches. Non-limiting examples of these approaches are briefly described below.

Homology to Known Sequences: To identify functional H. pylori nucleic acid and polypeptide sequences, a computer-assisted comparison of the claimed H. pylori sequences with previously published sequences that are in publicly available databases is useful. Obviously, protein coding sequences can be compared, for example, as a whole, and that a high degree of sequence homology between two proteins (such as more than 80 to 90%) at the amino acid level indicates that the two proteins also exhibit some degree of functional homology, such as between enzymes involved in metabolism, DNA synthesis or cell wall synthesis, and between proteins involved in transport, cell division, etc. In addition, many structural features of particular protein classes can be identified and aligned with specific consensus sequences, such as nucleotide, DNA, metal ion, and other small molecule binding domains; covalent modification sites such as phosphorylation, acylation, and the like; protein-protein interaction sites, etc. These consensus sequences may be quite short and thus may represent (en fraction of the entire protein coding sequence. Identification of such traits in the H. pylori sequence is therefore useful in determining the function of the encoded protein and in identifying useful targets for antibacterial drugs.

Of particular importance to the present invention are structural features that are common to secretory, transmembrane and surface proteins, including secretory signal peptides and hydrophobic transmembrane domains. H. pylori proteins, which have been determined to contain probable signal sequences and / or transmembrane domains, are very useful as immunogenic components of vaccines.

Identification of essential genes: Nucleic acids that encode proteins that are essential for the growth or viability of H. pylori are preferred as drug targets. H. pylori genes can be tested for their biological relevance to the body by examining the effect of deletion and / or gene disruption, i.e., the so-called gene knock-out, using techniques known to those skilled in the art. In this way, essential genes can be identified.

Strain Specific Sequences: It is believed that due to the evolutionary relationship between different H. pylori strains, the presently described H. pylori sequences may be useful in identifying and / or distinguishing between previously known and novel H. pylori strains. Other H. pylori strains are believed to exhibit at least 70% sequence homology with the sequence described herein. Systematic and routine analysis of DNA sequences derived from samples containing H. pylori strains and comparison with the present sequence allows identification of sequences that can be used to distinguish between strains as well as those that are common to all H. pylori strains. In one embodiment, the invention provides nucleic acids including probes, and peptide and polypeptide sequences that differentiate different H. pylori strains. Stem specific elements can also be identified functionally through their ability to elicit or react with antibodies that selectively recognize one or more H. pylori strains.

In another embodiment, the invention provides nucleic acids including probes and peptide and polypeptide sequences that are common to all H. pylori strains but are not found in other bacterial species.

Specific example: Determination of candidates for protein antigens for antibodies and vaccine development

Selection of protein antigen candidates for vaccine development may be derived from nucleic acids encoding H. pylori polypeptides. First, the ORFs can be analyzed for homology to other known exported or membrane proteins and analyzed using the discriminant analysis described by Klein, et al. (Klein, P., Kanehsia, M., and DeLisi, C. (1985) Biochimica et Biophysica Acta 815, 468-476) to predict exported and membrane proteins.

The homology survey can be performed using the BLAST algorithm contained in the Wisconsin Sequence Analysis Package (Genetics Computer Group, University Research Park, 575 Science Drive, Madison, W1 53711), comparing each putative amino acid sequence of the ORF with all sequences found in the current database. GenBank, SWISS-PROT and PIR. BLAST conducts a local match search between ORF and database sequences and reports a probable score that indicates the likelihood of this sequence being accidentally found in the database. An ORF with significant homology (e.g., with a probability that homology is only random, less than 1x10 ⁶ ) to membrane or exported proteins represents protein antigens for vaccine development. Based on sequence homology to genes cloned in other organisms, possible functions can be assigned to the H. pylori gene.

Discriminant analysis (Klein, et al. Supra) can be used to examine the amino acid sequences of ORFs. This algorithm uses its own information contained in the ORF amino acid sequence and compares it with information derived from the properties of known membrane and exported proteins. This comparison predicts which proteins will be exported, membrane associated or cytoplasmic. The ORF amino acid sequences identified by this algorithm as exported or membrane-associated are likely protein antigens for vaccine development.

The outer membrane proteins exposed on the surface are probably the best antigens to provide a protective immune response against H. pylori. Among the algorithms that can assist in predicting these outer membrane proteins is the presence of an amphipathic beta fold region at their C-terminus. This region, which has been detected in a large number of outer membrane proteins in gram-negative bacteria, is often characterized by hydrophobic residues (Phe or Tyr) at approximately positions 1, 3, 5, 7 and 9 from the C-terminus (see, for example, Figure 1, block F) . Importantly, these sequences were not detected at the C-terminus of the periplasmic proteins, so that they allow to pre-distinguish these classes of proteins based on primary sequence data. This phenomenon has been described by Struyve et al. (J. Mol. Biol. 218: 141-148, 1991).

Also shown in Figure 1 are additional amino acid sequence motifs found in many of the outer membrane proteins of H. pylori. The amino acid sequence alignment in Figure 1 shows portions of the sequences of five H. pylori proteins (indicated in the one letter amino acid code), indicated by their sequence identification numbers, and shown from N-terminal to C-terminal, from left to right. Six separate blocks (labeled A to F) with similar amino acid residues have been found that contain distinctive hydrophobic residues (Phe or Tyr; F or Y in the single letter amino acid residue code), which often occur at positions near the C-termini of the outer membrane proteins. The presence of several common motifs clearly demonstrates the similarity between members of this family of proteins.

In addition, outer cell wall proteins isolated from H. pylori often have a common motif near the mature N-terminus (ie after processing to remove the secretory signal), as illustrated by the blocked amino acid residues in Figure 2. Figure 2 shows the N-terminal portion of three proteins H.

pylori (indicated by their amino acid sequence identification numbers and displayed from N-terminal to C-terminal from left to right).

One of skill in the art will recognize that these common sequence motifs are highly significant and determine the similarity within this family of proteins.

Sometimes it is not possible to distinguish between several possible nucleotides at a given position in a nucleic acid sequence. In these cases, ambiguities are indicated by the extended alphabet as follows:

Following are the official one letter IUPAC-IUB base codes.

code Description of the base G guanine A adenine T thymine C cytosine R purine (A or G) Y pyrimidine (C or T or U) M amino (A or C) The ketone (G or T) WITH strong interaction (C or G) W weak interaction (A or T) H Not-G (A or C or T) B Not-A (C or G or T) IN No-T (no-U) (A or C or G) D Not-C (A or G or T) N whatever (A or C or G or T)

The translated double meaning codon is referred to as the letter "X" in the amino acid translations of the invention that include double meaning nucleic acids. In all cases, possible amino acid residues at a particular position are apparent from a nucleic acid sequence search based on the standard genetic code.

V. Production of H. pylori nucleic acid fragments and analogs and polypeptides

Based on the discovery of the H. pylori gene products of the invention, which are provided in the Sequence Listing, one skilled in the art can alter the claimed structures (H. pylori genes), e.g. by producing fragments or analogs thereof, and can test these newly formed structures for activity. Examples of techniques that are known to those skilled in the art and which allow the generation and testing of fragments and analogs are discussed below. These or analogous methods can be used to generate and search polypeptide libraries, e.g. random peptide libraries, or libraries of fragments or analogs of cellular proteins, for the ability to bind H. pylori polypeptides. Such scans are useful for identifying H. pylori inhibitors.

Generate fragments:

Protein fragments can be generated in several ways, e.g. recombinantly, by proteolytic cleavage, or by chemical synthesis. Internal or terminal fragments of a polypeptide can be generated by removing one or more nucleotides from one (for the terminal fragment) or both ends (for the internal fragment) of the nucleic acid that encodes the polypeptide. Expression of the mutated DNA creates polypeptide fragments. End-nibbling can thus generate DNAs that encode a number of fragments. DNAs that encode fragments of the protein can also be generated by random shearing, restriction digestion, or a combination of the above methods.

Fragments can also be chemically synthesized using techniques known in the art, such as conventional Merrifield f-Moc or t-Boc solid phase chemistry. For example, the peptides of the present invention may be arbitrarily divided into fragments of desired length without overlapping the fragments, or may be divided into overlapping fragments of desired length.

Change of nucleic acids and polypeptides: random methods

Variants of the amino acid sequence of a protein can be prepared by random mutagenesis of a DNA that encodes a protein or a particular domain or region of a protein. Useful methods include PCR mutagenesis and saturation mutagenesis. A library of random amino acid sequence variants can also be generated by synthesis of a set of degenerate oligonucleotide sequences. (A method for screening proteins in a variant library is also provided herein).

(A) PCR mutagenesis

In PCR mutagenesis, the accuracy of Taq polymerase is reduced to introduce random mutations into the cloned DNA fragment (Leung et al., 1989, Technique 1: 11-15). The DNA region to be mutated is amplified using a polymerase chain reaction (PCR) under conditions that reduce the accuracy of Taq DNA polymerase synthesis, e.g. using a dGTP / dATP ratio of 5 and adding Mn ²⁺ to the PCR reaction mixture. The pool of amplified DNA fragments is then incorporated into appropriate cloning vectors to create random mutant libraries.

(B) Saturation mutagenesis

Saturation mutagenesis allows for the rapid incorporation of a large number of single base substitutions into cloned DNA fragments (Mayers et al., 1985, Science 229: 242). This technique involves the generation of mutations e.g. by in vitro chemical treatment or irradiation of single stranded DNA, and synthesis of complementary DNA strand. The frequency of mutations can be modulated by modulating the hardness of the treatment, and virtually all possible base substitutions can be obtained. Since this process does not involve genetic selection for mutant fragments, both neutral substitutions and those that alter function are obtained. The point mutation distribution is not directed to conservative sequence elements.

(C) degenerate oligonucleotides

The homolog library may also be constructed from a set of degenerate oligonucleotide sequences. Chemical synthesis of degenerate sequences can be performed in an automated DNA synthesizer and the synthetic genes can be ligated into an appropriate expression vector. The synthesis of degenerate oligonucleotides is known in the art (see, for example, Narang, SA (1983) Tetrahedmn 39: 3; Itakura et al. (1981) Recombinant DNA, Proc 3rd Cleveland Sympos. Macmmolecules, ed. AG Walton, Amsterdam: Elsevier p. 273). Itakura et al (1984) Annu Rev. Biochem 53: 323; itakura et al (1984) Science 198: 1056; Ike et al (1983) Nucleic Acid Res 11: 477. be used in the directed evolution of other proteins (see, for example, Scott et al. (1990) Science 249: 386-390; Roberts et al. (1992) PNAS 89: 2429-2433; Devlin et al. (1990) Science 249: 404- 406 (Cwiria et al. (1990) PNAS 87: 6378-6382; as well as US Patent Nos. 5,223,409, 5,198,346 and 5,096,815).

Change of nucleic acids and polypeptides: Methods of directed mutagenesis

Non-random or directed mutagenesis techniques can be used to provide specific sequences or mutations in specific regions. These techniques can be used to generate variants that include e.g. deletions, insertions, or substitutions of residues of a known amino acid sequence of a protein. The mutation sites may be modified individually or in series, e.g. (1) substitution by conservative amino acids, and then more radical options depending on the results achieved; (2) deletion of the target residue, or (3) insertion of residues of the same or different class into a designated site, or a combination of options 1 to 3.

(A) Alanine scanning mutagenesis

Alanine scanning mutagenesis is a useful method for identifying certain residues or regions of a desired protein that are preferred sites or domains for mutagenesis, Cunningham and Wells (Science 244: 1081-1085, 1989). In alanine scanning, a residue or group of target residues (e.g., charged residues such as Arg, Asp, His, Lys, and Glu) are identified and exchanged with a neutral or negatively charged amino acid (most preferably alanine or polyalanine). Amino acid substitution may affect the interaction of amino acids with the aqueous environment surrounding them or the cell exterior. Those domains that exhibit functional sensitivity to substitutions are then improved by introducing additional or other variants at the substitution sites. Thus, while the site of introduction of the amino acid sequence variation is predetermined, the nature of the mutation itself may not be predetermined. For example, to optimize the course of a mutation at a given site, alanine scanning or random mutagenesis can be performed at the target codon or region, and the expressed desired protein subunit variants are screened for optimal combination of desired activity.

(B) Oligonucleotide-mediated mutagenesis

Oligonucleotide-mediated mutagenesis is a useful method for preparing DNA substitution, deletion and insertion variants, see e.g. Adelman et al., (DNA 2: 183,1983). Briefly, the DNA of interest is altered by hybridizing the oligonucleotide encoding the mutation to the DNA template, wherein the template is a single-stranded form of a plasmid or bacteriophage that contains an unchanged or natural DNA sequence of the protein of interest. Following hybridization, DNA polymerase is used to synthesize the entire second complementary strand of the template, which thus contains the oligonucleotide primer, and will thus encode a selected change in the DNA of the desired protein. In general, oligonucleotides of at least 25 nucleotides in length are used. The optimal oligonucleotide will have from 12 to 15 nucleotides that are completely complementary to the template on each side of the nucleotide that encodes the mutation. This ensures that the oligonucleotide will properly hybridize to the single-stranded template molecule

DNA. Oligonucleotides are commonly synthesized using techniques known in the art, such as described by Crea et al. (Proc. Natl. Acad. Sci. USA, 75: 5765 [1978j]).

(C) Cassette mutagenesis

Another method for preparing variants - cassette mutagenesis - is based on the technique described by Welis et al. (Gene 34: 315 [1985]). The starting material is a plasmid (or other vector) that contains the DNA of the protein subunit to be mutated. The DNA codon of the protein subunit to be mutated is identified. There must be a unique restriction endonuclease site on each side of the designated mutation site (s). If such sites do not exist, they can be generated using the oligonucleotide-directed mutagenesis method described above to introduce them into the appropriate DNA sites of the desired protein subunit. After the restriction sites have been introduced into the plasmid, the plasmid is linearized by cleavage at these sites. A double stranded oligonucleotide that encodes the DNA sequence between the restriction sites but contains the desired mutations) is synthesized using standard procedures. The two strands are synthesized separately and then hybridized together using standard techniques. This double-stranded oligonucleotide is referred to as a cassette. This cassette is designed so that its 3 'and 5' ends are compatible with the ends of the linearized plasmid so that it can be directly ligated into the plasmid. This plasmid now contains a mutated DNA sequence of the desired protein subunit.

(D) Combination mutagenesis

Combination mutagenesis can also be used to generate mutants (Ladner et al., WO 88/06630). In this method, the amino acid sequences of a group of homologs or other related proteins are preferably aligned so as to achieve the highest possible homology. All amino acids that are located at a given position in the aligned sequences can be selected to generate a degenerate set of combination sequences. Combination mutagenesis generates a varied library of variants at the nucleic acid level and is encoded by a varied gene library. For example, a mixture of synthetic oligonucleotides may be enzymatically ligated into gene sequences such that the degenerate set of potential sequences is expressible in the form of individual peptides or alternatively in the form of a set of larger fusion proteins that contain a set of degenerate sequences.

Other modifications of H. pylori nucleic acids and polypeptides

It is possible to modify the structures of the H. pylori polypeptide to increase solubility, enhance stability (e.g., ex vivo storage time and resistance to proteolytic degradation in vivo). As described herein, a modified H. pylori protein or peptide may be made in which the amino acid sequence has been altered, for example, by amino acid substitution, deletion, or addition.

The H. pylori peptide can also be modified by substitution of cysteine residues, preferably with alanine, serine, threonine, leucine or glutamic acid residues, thereby minimizing dimerization through disulfide bonds. In addition, the amino acid side chains of the protein fragments of the invention may be chemically modified. Another modification is cyclization of the peptide.

In order to increase the stability and / or reactivity of the H. pylori polypeptide, it can be modified by incorporating one or more polymorphisms into the amino acid sequence of the protein resulting from any natural allelic variation. In addition, within the scope of the invention, D-amino acids, unnatural amino acids, or non-amino acid analogs may be substituted or added to produce the modified protein. Further, the H. pylori polypeptide can be modified using polyethylene glycol (PEG) according to Method A. Sehon et al. (Wie et al., Supra) to form a PEG conjugated protein. In addition, PEG may be added during chemical protein synthesis. Other modifications of H. pylori proteins include reduction / alkylation (Tarr, Methods of Protein Microcharacterization, J. E. Silver ed., Humana Press, Clifton NJ 155-194 (1986)); acylation (Tarr, supra); chemical coupling with the appropriate carrier (Mishell and Shiigi, eds., Selected Methods in Cellular Immunology, W.H.

Freeman, San Francisco, CA (1980); U.S. Patent 4,939,239; or mild formalin treatment (Marsh, (1971) Int. Árch. of Allergy and Appl. Immunol., 41; 199-215).

To facilitate purification and potentially increase the solubility of the H. pylori protein or peptide, it is possible to add an amino acid fusion moiety to the peptide backbone. For example, hexa-histidine can be added to a protein for purification by immobilized metal ion affinity chromatography (Hochuli, E. et al., (1988) Bio / Technology, 6: 1321-1325). In addition, to facilitate isolation of peptides without irrelevant sequences, specific endoprotease cleavage sites may be located between the fusion sequence and the peptide.

To potentially help correct antigenic processing of epitopes within the H. pylori polypeptide, canonical protease-sensitive sites may be projected between regions each containing at least one epitope by recombinant or synthetic methods. For example, charged amino acid pairs, such as KK or RR, may be included between regions within a protein or fragment during their recombinant construction. The resulting peptide may be sensitive to cleavage by cathepsin and / or other trypsin-like enzymes that may form portions of the protein containing one or more epitopes. In addition, such charged amino acid residues may increase the solubility of the peptide.

Primary methods for screening polypeptides and analogs

Various techniques for screening mutant gene products are known in the art. Techniques for screening large gene libraries often include cloning a gene library into expression vectors that are capable of replicating, transforming the respective cells with the resulting library in vectors, and expressing the genes under conditions in which detection of the desired activity, e.g. in this case, binding of the polypeptide or interacting protein of H. pylori facilitates the relatively simple isolation of the vector encoding the gene whose product has been detected. Each of the techniques described below is adaptable to high throughput analysis to search a large number of sequences generated e.g. by random mutagenesis techniques.

(A) Two-hybrid system

A two-hybrid assay such as the system described above (also with other screening methods described herein) can be used to identify peptides, e.g. fragments or analogs of a naturally occurring H. pylori polypeptide, e.g. cell proteins or randomly generated polypeptides that bind H. pylori protein. (The H. pylori domain is used as bait protein and the variant library is expressed as captured fusion proteins). In an analogous manner, the two-hybrid assay (also with other screening methods described herein) can be used to detect polypeptides that bind H. pylori polypeptide.

(B) Display Libraries

In one screening procedure, candidate peptides are displayed on the surface of a cellular or viral particle, and the ability of certain cellular or viral particles to bind the respective receptor protein through the exposed product is detected by "plating". For example, a gene library can be cloned into the bacterial cell surface membrane protein gene and the resulting fusion protein can be detected by plating (Ladner et al., WO 88/06630; Fuchs et al. (1991) Biophysics 9: 1370-1371; and Goward et al. (1992) TIBS 18: 136-140). In a similar method, a detectably labeled ligand can be used to capture potentially functional peptide homologs. Fluorescent labeled ligands, e.g. receptors can be used to detect homologues that retain ligand binding activity. The use of fluorescently labeled ligands allows the bots of the cell to be examined visually and separated under a fluorescent microscope or, if the cell morphology so permits, separated by a fluorescent activated cell sorter.

The gene library can be expressed as a fusion protein on the surface of the viral particle. For example, in a filamentous phage system, foreign peptide sequences can be expressed on the surface of infectious phage, resulting in two significant advantages. First, since these phages can be used as affinity matrices at a concentration well above 10 ¹³ phages per milliliter, a large number of phages can be searched at once. Second, since each infectious phage carries a gene product on its surface, if a certain phage is obtained from a low yield affinity matrix, it can be amplified in another infectious cycle. In phage display libraries, a group of nearly identical E. coli filamentous phages M13, fd and f1 is most commonly used. Both glll and gVIII coat phage proteins can be used to generate fusion proteins without disrupting the necessary packaging of the viral particle. Foreign epitopes can be expressed at the NH ₂ -terminus of pIII, and phage carrying such epitopes can be obtained from a large excess of phages without this epitope (Ladner et al. PCT Publication WO 90/02909; Garrard et al., PCT Publication WO 92/09690; Marks et al (1992) J. Biol Chem 267: 16007-16010 Griffiths et al (1993) EMBO J 12: 725-734 Clackson et al (1991) Nature 352: 624628 and Barbas et al (1992) PNAS 89: 4457-4461.

Conventional approaches use the E. coli maltose receptor (outer membrane protein, LamB) as a partner for peptide fusion (Charbit et al. (1986) EMBO 5, 3029-3037). Oligonucleotides were incorporated into plasmids encoding the LamB gene to generate peptides fused to one of the extracellular loops of the protein. These peptides are available for binding with ligands, e.g. antibodies, and may elicit an immune response when cells are administered to animals. Other cell surface proteins, e.g. OmpA (Schorr et al. (1991) Vaccines 91, pp. 387-392), PhoE (Agterberg, et al. (1990) Gene 88, 37-45), and PAL (Fuchs et al. (1991) Bio / Tech 9, 1369-1372), as well as large bacterial surface structures, served as vehicles for peptide exposure. The peptides can be fused with pilin, a protein that polymerizes to form pilus, a tube for the inter-bacterial exchange of genetic material (Thiry et al. (1989) Appl. Environ. Microbiol. 55, 984-993). Since it plays a role in interaction with other cells, pilus provides a useful carrier for presenting peptides to the extracellular environment. Another large surface structure used for the peptide display is a bacterial movement organ, the flagellum. Fusion of peptides to the flagellin protein subunit provides a dense array of many peptide copies on host cells (Kuwajima et al. (1988) Bio / Tech. 6, 1080-1083). Surface proteins of other bacterial species have also served as partners for peptide fusion. Examples include protein A from Staphylococcus and the outer membrane IgA protease Neisseria (Hansson et al. (1992) J. Bacteriol. 174, 4239-4245 and Klauser et al. (1990) EMBO J. 9,1991-1999).

In the filamentous phage systems and in the La m B system described above, there is a physical association between the peptide and its coding DNA through the DNA content within the particle (cell or phage) that carries the peptide on its surface. By trapping the peptide, particles are trapped, with the DNA inside. An alternative method uses the Lac-DNA-binding protein (Cull et al. (1992) PNAS USA 89: 18651869) to establish a peptide-DNA connection. This system uses a plasmid that contains the Lac1 gene with an oligonucleotide cloning site at the 3 'end. The protein fused to the Lac1 peptide is produced by controlled induction of arabinose. This phtizia retains the natural ability of Lac1 to bind to a short DNA sequence known as the LacO operator (LacO). By introducing two copies of LacO into the expression plasmid, it is achieved that the Lac1-peptide fusion binds tightly to the plasmid encoding it. Since plasmids in each cell contain only one oligonucleotide sequence and each cell expresses only one peptide sequence, the peptides are specifically and stably associated with the DNA sequence that directs their synthesis. Library cells are gently lysed and peptide-DNA complexes are exposed to a matrix of immobilized receptors to obtain complexes containing active peptides. The associated DNA is then reintroduced into the cells for amplification and the DNA sequenced to determine the identity of the peptide ligands. As a demonstration of the practical utility of this method, a large library of random dodecapeptides was produced and selected on a monocional antibody against the opioid peptide of dynorphin B. A group of peptides were obtained, all related to containing a consensus sequence corresponding to the six residual portion of dynorphin B (Cull et al. (1992) Proc Natl Acad Sci Sci USA 89-1869).

This system, sometimes referred to as peptides on plasmids, differs from two-way phage display methods. First, the peptides are attached to the C-terminus of the fusion protein, as a result of which the library members are exposed as free carboxyl-terminus peptides. Both filamentous phage coat proteins, both pIII and pIII, are anchored to the phage at their C-terminus, and the host proteins are positioned such that their N-terminal domains are directed outward. In some designs, phage-exposed proteins are present directly at the amino terminus of the fusion protein (Cwirla, et al. (1990) Proc. Natl. Acad. Sci. U.S.A. 87, 6378-6382). The second difference is the set of biological tendencies that affect the population of peptides actually present in libraries. Lac1 fusion molecules are trapped in the cytoplasm of the host cells. Phage coat fusions are rapidly exposed to the cytoplasm during translation, but are rapidly secreted across the inner membrane into the periplasmic compartment, while remaining anchored in the membrane by their terminal hydrophobic domains, with N-termini that contain peptides protruding into the periplasm while waiting for phages to form . Peptides in Lac1 and phage libraries can vary significantly due to their exposure to various proteolytic activities. Phage coat proteins require transport across the inner membrane and signal peptidase processing as an introduction prior to incorporation into the phage. Certain peptides have a detrimental effect on these processes and are less common in libraries (Gallop et al. (1994) J. Med. Chem. 37 (9): 1233-1251). These particular tendencies do not play a role in the Lacl display system.

The number of small peptides available in recombinant random libraries is enormous. Libraries of 10 ⁷ to 10 ⁹ independent clones are routinely prepared. Libraries having a size of 10 ¹¹ recombinants were generated, but this size approaches the practical limit of clone libraries. This limitation of the size of the library occurs in the step of transforming DNA that contains random segments into host bacterial cells. To circumvent this limitation, an in vitro system based on exposure of nascent peptides in polyzom complexes has been developed. This dispersion library method has the potential to create libraries that are 3 to 6 orders larger than the currently available phage / phagemid or plasmid libraries. In addition, library construction, peptide expression, and screening are performed in a completely cell-free format.

Using another method (Gallop et al. (1994) J. Med. Chem. 37 (9): 1233-1251), a molecular DNA library encoding 10 ¹² decapeptides was constructed and the library was expressed in E. coli S30 in vitro linked transcriptional / translation system. The conditions were selected such that the ribosomes were retained on the mRNA, thereby accumulating a substantial portion of the RNA in the polysomes and yielding complexes containing the nascent peptides still associated with their coding RNA. Polysomes were robust enough to be affinity purified at immobilized receptors, mostly in the same way as conventional recombinant peptide display libraries are searched. RNA from the bound complexes is removed, converted to cDNA, and amplified by PCR, thereby forming a template for the next round of synthesis and screening. The polysome display method may be associated with a phage display system. After several rounds of screening, cDNA from an enriched pool of polysomes was cloned into a phagemid vector. This vector serves both as a peptide expression vector that exposes peptides fused to coat proteins and as a DNA sequencing vector to identify the peptide. By expressing polyosome-derived peptides on phage, either the affinity selection procedure can be continued in this manner, or the peptides in individual clones can be tested for binding activity in phage ELISA, or for binding specificity in complete phage ELISA (Bairet, et al. (1992) (Anal Biochem 204, 357-364). The DNA generated by the phagemid host is sequenced to determine the sequences of the active peptides.

Secondary search of polypeptides and analogs

The highly efficient procedures described above may be followed by secondary scans to identify other biological activities, e.g. they allow the skilled artisan to distinguish agonists from antagonists. The type of secondary crawl used will depend on the activity you want to test. For example, a method may be developed in which the ability to inhibit the interaction between a target protein and its corresponding ligand can be used to determine antagonists in a group of peptide fragments that have been isolated in one of the primary scans described above.

Thus, methods for generating fragments and analogs and testing them for their activity are known in the art. Once the nucleus of the target sequence is identified, obtaining analogs and fragments is routine to one of skill in the art.

Peptide mimetics of H. pylori polypeptides

The invention also provides for reducing the protein binding domains of the subject H. pylori polypeptides, thereby generating mimetics, e.g. peptide or non-peptide agents. Peptide mimetics are capable of disrupting the binding of a polypeptide to its opposite ligand, e.g. in the case of a H. pylori polypeptide binding a naturally occurring ligand. It is possible to determine the critical residues in the subject H. pylori polypeptide that are involved in the molecular recognition of the polypeptide and can be used to generate H. pylori-derived peptidomimetics that competitively or non-competitively inhibit binding of the H. pylori polypeptide to the interacting polypeptide. EP-412 762A and EP-B31 080A).

For example, scanning mutagenesis may be used to map the amino acid residues of a particular H. pylori polypeptide that are involved in binding an interacting polypeptide. Peptomimetic compounds (e.g., diazepine or isoquinoline derivatives) may be formed which mimic these residues when binding to an interacting polypeptide, and thus may inhibit binding of the H. pylori polypeptide to the interacting polypeptide and thus affect the function of the H. pylori polypeptide. For example, peptide analogs of such residues that cannot be hydrolyzed can be generated using benzodiazepine (e.g., see Freidinger et al. In Peptides: Chemistry and Biology, GR Marshall ed., ESCOM Publisher: Leiden, Netherlands, 1988), azepine (e.g. Huffman et al in Peptides: Chemistry and Biology, GR Marshall ed., ESCOM Publisher: Leiden, Netherlands, 1988), substituted gamma lactam rings (Garvey et al. In Peptides: Chemistry and Biology, GR Marshall ed., ESCOM Publisher: Leiden, Netherlands, 1988), keto-methylene pseudopeptides (Ewenson et al. (1986) J Med Chem 29: 295; and Ewenson et al. In Peptides: Structure and Function (Proceedings of the 9th American Peptide Symposium)) Pierce Chemical Co. Rockland, IL, 1985), β-coiled dipeptide nuclei (Nagai et al. (1985) Tetrahedron Lett 26: 647; and Sato et al. (1986) J Chem Soc Perkin Trans 1: 1231), and β-aminoalcohols (Gordon et al. (1985) Biochem Biophys Res Commun 126: 419 and Dann et al (1986) Biochem Biophys Res Commun 134: 71).

VI. H. pylori vaccine preparations of nucleic acids and polypeptides

The invention also relates to vaccine compositions or preparations (interchangeable herein) for protection against H. pylori infection or for treating infection

H. pylori. The term "treatment of H. pyloid infection" as used herein means the therapeutic treatment of an existing or established H. pylori infection. The term "protection against H. pyloid infection or" preventive treatment "means the use of a vaccine preparation of H. pylori to reduce the risk or prevent infection if there is a risk of H. pylori infection. In one embodiment, the vaccine compositions comprise one or more immunogenic components, such as a H. pylori surface protein, or a portion thereof, and a pharmaceutically acceptable carrier. For example, in one embodiment, the vaccine compositions of the invention comprise at least one H. pylori polypeptide or a combination thereof, or fragments thereof from the same or different H. pylori antigens. H. pylori nucleic acids and polypeptides for use in the vaccine compositions of the invention include the nucleic acids and polypeptides set forth in the Sequence Listing, preferably those H. pylori nucleic acids that encode surface proteins or fragments thereof. For example, the preferred H. pylori nucleic acid and polypeptide for use in the vaccine composition of the invention is selected from the group of nucleic acids that encode the cell envelope proteins and the H. pylori cell envelope proteins shown in the table.

However, any nucleic acid encoding an immunogenic H. pylori protein and an H. pylori polypeptide, or a portion thereof, may be used in the present invention. These vaccines have therapeutic and / or prophylactic uses.

In one aspect, the invention provides a vaccine composition for protection against H. pylori comprising at least one immunogenic fragment of H. pylori protein and a pharmaceutically acceptable carrier. Preferred fragments include peptides of at least about 10 amino acid residues in length, preferably about 10 to 12 amino acid residues, and more preferably about 12 to 16 amino acid residues.

For example, the immunogenic components of the invention can be obtained by screening for polypeptides that have been recombinantly generated from the appropriate nucleic acid fragments that encode the entire H. pylori protein. In addition, the fragments can be chemically synthesized using techniques known in the art, such as conventional Merrifield f-Moc or t-Boc solid phase chemistry.

In another embodiment, the immunogenic components are identified through the ability of the peptide to stimulate T cells. Peptides that stimulate T cells, as determined by determining, for example, T cell proliferation or cytokine secretion, are defined herein as peptides comprising at least one T cell epitope. It is believed that T cell epitopes are involved in initiating and maintaining an immune response to a protein allergen that is responsible for the clinical symptoms of allergy. These T cell epitopes are considered to trigger early events at the T helper cell level by binding the respective HLA molecule to the surface of antigen-presenting cells, thereby stimulating T cell subpopulation with the respective T cell epitope receptor. These events lead to T cell proliferation, lymphokine secretion, local inflammatory responses, the collection of additional immune cells at the site of antigen-T cell interaction, and activation of the B cell cascade that leads to antibody production. The T cell epitope is the essential element, or the smallest unit, that is recognized by the T cell receptor, wherein the epitope includes amino acids necessary for receptor recognition (e.g., about 6 or 7 amino acid residues). Amino acid sequences that mimic these T cell epitopes are within the scope of this invention.

In another embodiment, the immunogenic components of the invention are identified through genomic vaccination. The basic protocol is based on the idea that the expression of libraries consisting of all parts of the genome of the pathogen, e.g. The H. pylori genome can mediate protection when used to genetically immunize a host. This immunization with an expression library (ELI) is analogous to expression cloning and involves the incorporation of a genomic expression library of a pathogen, e.g. H. pylori, into plasmids that act as genetic vaccines. Plasmids can also be designed to encode a genetic adjuvant that can significantly stimulate a humoral response. These genetic adjuvants may be incorporated at separate sites and may act both extracellularly and intracellularly.

It is a new approach in vaccine production that has many benefits of living / attenuated pathogens but does not carry any risk of infection. The expression library of pathogenic DNA is used to immunize the host, thereby causing a risk-free presentation of the live vaccine antigen. For example, in the present invention, random fragments of the H. pylori genome or cosmid or plasmid clones, as well as PCR products of genes identified by genome sequencing can be used to immunize the host. The feasibility of this method has been demonstrated on Mycoplasma pulmonis (Bány et al., Nature 377: 632-635, 1995), where, although only partial expression of libraries of Mycoplasma pulmonis, a natural rodent pathogen, has provided protection against the pathogen.

ELI is a technique that allows the production of non-infectious multipartite vaccines, although little is known about the pathogen biology, since ELI uses the immune system to search for gene candidates. When these genes are isolated, they can be used as genetic vaccines or for the development of recombinant protein vaccines. Thus, ELI allows the production of vaccines in a systematic, mostly mechanized manner.

The screening of the immunogenic components can be performed using one or more different methods. For example, in vitro peptide T cell stimulatory activity is assayed by contacting a peptide known or believed to be immunogenic, with an antigen-presenting cell that presents the respective MHC molecules, in a T cell culture. Presentation of the immunogenic H. pylori peptide associated with the respective MHC molecules to T cells together with the necessary stimulation causes signal transduction into the T cell, which induces increased production of cytokines, especially interleukin-2 and interleukin-4. Culture supernatant can be harvested and assayed for interleukin-2 or other known cytokines. For example, any of several common methods for interleukin-2 can be used, such as the assay described in Proc. Natl. Acad. Sci USA, 86: 1333 (1989), the important parts of which are incorporated herein by reference. A kit for assaying interferon production is also available from Genzyme Corporation (Cambridge, MA).

Alternatively, a conventional T cell proliferation assay requires measurement of the incorporation of tritiated thymidine. T cell proliferation can be measured in vitro by determining the amount of ³ H-labeled thymidine that is incorporated into the replicating

DNA of cultured cells. Thus, it is possible to quantify the rate of DNA synthesis and hence the rate of cell division.

The vaccine compositions or compositions of the invention comprising one or more immunogenic components (e.g., an H. pylori polypeptide or fragment thereof, or a nucleic acid encoding an H. pylori polypeptide or fragment thereof) preferably comprise a pharmaceutically acceptable carrier. The term "pharmaceutically acceptable carrier" is meant to include any and all solvents, dispersing media, coating agents, antibacterial and antifungal agents, isotonic and absorption delaying agents and the like that are compatible with pharmaceutical administration. Suitable pharmaceutically acceptable carriers include, for example, one or more of water, saline, phosphate buffered saline, dextrose, glycerol, ethanol, and the like, as well as combinations thereof. Pharmaceutically acceptable carriers may further comprise minor amounts of additives, such as wetting or emulsifying agents, preservatives, and buffers, which increase the storage time and efficiency of the H. pylori nucleic acid or polypeptide. For vaccine compositions of the invention comprising H. pylori polypeptides, the polypeptides are preferably administered together with a suitable adjuvant and / or delivery system described herein.

One of skill in the art will recognize that a therapeutically effective amount of the DNA or protein of the invention will depend inter alia on the mode of administration, the dosage unit of the nucleic acid or H. pylori polypeptide administered, whether the protein or nucleic acid is administered in combination with other therapeutic agents. agents, the immune status and health of the patient, and the therapeutic activity of a particular protein or nucleic acid.

Vaccine formulations are commonly administered parenterally, e.g. by injection either subcutaneously or intramuscularly. Methods of intramuscular immunization are described in Wolff et al. (1990) Science 247: 1465-1468 and Sedegah et al. (1994) Immunology 91: 9866-9870. Other routes of administration include oral and pulmonary formulations, lace, and transdermal applications. To induce protection against H. pylori infection, oral immunization is preferable to parenteral methods of Czinn et. al. (1993) Vaccine 11: 637-642. Oral formulations contain normally used excipients such as pharmaceutical grades of mannitol, lactose, starch, magnesium stearate, sodium saccharin, cellulose, magnesium carbonate, and the like.

In one embodiment, the vaccine composition comprises an adjuvant as a pharmaceutically acceptable carrier. Examples of suitable adjuvants for use in the vaccine compositions of the invention include, but are not limited to, aluminum hydroxide; Nacetyl-muramyl-L-threonyl-D-isoglutamine (thr-MDP); N-acetyl-nor-muramyl-L-alanyl-D-isoglutamine (CGP 11637, referred to as nor-MDP); N-acetylmuramyl-L-alanyl-D-isoglutaminyl-L-alanine-2- (1 '-2'-dipalmitoyl-sn-glycero-3-hydroxyphosphoryloxy) ethylamine (CGP 19835A, referred to as MTP-PE); RIBI, which contains three components from a bacterium; monophosphoryl lipid A; trehalose dimycoloate; cell wall skeleton (MPL + TDM + CWS) in 2% squalene / Tween 80 emulsion; and cholera toxin. Others that may be used are nontoxic derivatives of cholera toxin, including its B subunit, and / or conjugates or genetically engineered fusions of H. pylori polypeptide with cholera toxin or its B subunit, procholeragenoid, fungal polysaccharides, including schizophylan, muramyl dipeptide, muramyl dipeptide derivatives, phorbol esters, labile toxins of E. coli, non-H. pylori bacterial lysates, block polymers or saponins.

In another embodiment, the vaccine composition comprises a delivery system as a pharmaceutically acceptable carrier. Suitable delivery systems for use in the vaccine compositions of the invention include biodegradable microcapsules or immunostimulatory complexes (ISCOMs), cochleate or liposomes, genetically engineered attenuated live vectors such as viruses or bacteria, and recombinant (chimeric) virus-like particles, e.g. "Bluetongue. In another embodiment, the vaccine composition comprises both a delivery system and an adjuvant.

The delivery system in humans may include enteric-release capsules that protect the antigen from the acidic environment of the stomach, and contain the H. pylori polypeptide in insoluble form as a fusion protein. Suitable carriers for the vaccines of the invention are enteric-coated capsules and polyactin-glycolide microspheres. Suitable diluents are 0.2 N NaHCO ₃ and / or physiological saline.

The vaccines of the invention may be administered as a primary prophylactic agent to adults or children, as a secondary prevention following successful eradication of H. pylori in an infected host, or as a therapeutic agent for inducing an immune response in a susceptible host to prevent H. pylori infection. The vaccines of the invention are administered in amounts readily determined by one skilled in the art. Thus, a suitable adult dose will be in the range of 10 µg to 10 g, preferably 10 µg to 100 mg, for example 50 µg to 50 mg. A suitable adult dose will also be in the range of 5 µg to 500 mg. Similar dosage ranges will be applicable to children.

The amount of adjuvant used will depend on the type of adjuvant used. For example, when the mucosal adjuvant is cholera toxin, it is suitably used in an amount of from 5 pg to 50 pg, for example in an amount of 10 pg to 35 pg. When used in the form of microcapsules, the amount used to achieve the desired dosage will depend on the amount found in the microcapsule matrix. Determination of this amount is within the skill of the art.

Those skilled in the art will appreciate that the optimal dose will more or less depend on the patient's body weight, disease, route of administration, and other factors. It will also be appreciated by those skilled in the art that appropriate dose levels can be obtained based on results relating to known oral vaccines, such as E. coli lysate-based vaccines (6 mg daily dose up to a total of 540 mg) and enterotoxin purified. E. coli antigen (4 doses of 1 mg each) (Schulman et al., J. Urol. 150: 917-921 (1993)); Boedecker et al., American Gastroenterological Assoc. 999.A-222 (1993)). The number of doses will depend on the disease, formulation, and efficacy data from clinical cases. Without intending to limit the method of treatment in any way, treatment may be provided by more than 3 to 8 doses under a primary immunization regimen of more than 1 month (Boedeker, American Gastroenterological Assoc. 888: A-222 (1993)).

In a preferred embodiment, the vaccine composition of the invention may be based on a composition comprising whole killed E. coli with an immunogenic fragment of an H. pylori protein of the invention that is expressed on its surface, or may be based on an E. coli lysate in which E. coli is killed. coli serves as a carrier or adjuvant.

It will be appreciated by those skilled in the art that some vaccine compositions of the invention are useful only for the prevention of H. pylori infection, some are useful only for the treatment of H. pylori infection, and some are useful for both the prevention and treatment of H. pylori infection . In a preferred embodiment, the vaccine composition of the invention provides protection against H. pylori infection by stimulating humoral and / or cell-mediated immunity against H. pylori. Of course, the desired clinical goal is to ameliorate any symptoms of H. pylori infection, including reducing the doses of drugs used to treat H. pylori caused by the disease, or increasing antibody production in the serum or mucosa of patients.

VII. Antibodies reactive with H. pylori polypeptides

The invention also encompasses antibodies specifically reacting with the subject H. pylori polypeptide. Anti-protein / anti-peptide antisera or monoclonal antibodies can be made by standard procedures (see, for example, Antibodies: A Laboratory Manual ed. By Harlow and Lane (Cold Spring Harbor Press: 1988)). Mammals such as mice, hamsters and rabbits can be immunized with an immunogenic form of the peptide. Techniques to ensure immunogenicity of a protein or peptide, including conjugation to carriers, or other techniques are known in the art. The immunogenic portion of the subject H. pylori polypeptide can be administered in the presence of an adjuvant. The progress of the immunization can be monitored by detecting antibody titers in plasma or serum. Standard ELISA or other immunoassays with an immunogen as an antigen can be used to detect antibody levels.

In a preferred embodiment, the subject antibodies are immunospecific for antigenic determinants of H. pylori polypeptides of the invention, e.g. antigenic determinants of a polypeptide of the invention that is included in the Sequence Listing or for a closely related human or non-human mammalian homologue (e.g., 90% homology, more preferably at least 95% homology). In yet another preferred embodiment, the anti-H. pylori antibodies do not substantially cross-react (i.e., react specifically) with a protein that is, for example, less than 80% homologous to the sequence of the invention contained in the Sequence Listing. By "substantially non-cross-reactive" is meant that the binding affinity of the antibody to the non-homologous protein is less than 10%, more preferably less than 5%, and even more preferably less than 1% of the binding affinity for the protein of the invention. In the most preferred embodiment, there is no cross-reaction between bacterial and mammalian antigens.

As used herein, an antibody is intended to include fragments thereof that also specifically react with H. pylori polypeptides. Antibodies can be fragmented using conventional techniques, and fragments can be screened for utility in the same manner as described above for whole antibodies. For example, F (ab ') 2 may be generated by treating the antibody with pepsin. The resulting F (ab ') 2 fragment can be treated to reduce disulfide bridges to form Fab' fragments. In addition, the antibodies of the invention are intended to include bispecific and chimeric molecules having anti-H. pylori part.

Both monoclonal and polyclonal antibodies (Ab) directed against H. pylori polypeptides or H. pylori polypeptide variants, and antibody fragments such as Fab'a F (ab ') ₂ , can be used to block the effect of H. pylori polypeptide, by microinjection anti-H. pylori polypeptide antibodies of the present invention, studying the role of a particular H. pylori polypeptide of the invention in aberrant or unwanted intracellular signaling as well as normal cellular function of H. pylori.

Antibodies that specifically bind H. pylori epitopes can also be used to immunohistochemically stain tissue samples, to assess the amount and type of expression of H. pylori antigens. Anti H. pylori polypeptide antibodies can be used for diagnosis, immunoprecipitation and immunoblotting to detect and evaluate H. pylori levels in tissue or body fluid as part of a clinical testing procedure. In a similar manner, the ability to monitor levels of an H. pylori polypeptide in an individual may allow the efficacy of a given treatment regimen to be determined in an individual suffering from such a disorder. The level of H. pylori polypeptide may be measured in cells found in body fluid, for example urine samples, or may be measured in tissues obtained, for example, by gastric biopsy. Diagnostic tests using anti-tf. pylori antibodies may include, for example, immunoassays designed to early diagnose H. pylori infections. The present invention can also be used as a method for detecting antibodies that are contained in samples from individuals infected with this bacterium using specific H. pylori antigens.

The anti-H. The pylori polypeptide antibodies of the invention can also be used to immunologically screen cDNA libraries that are incorporated into expression vectors such as Xgt11, λ18-23, λΖΑΡ and XORF8. Mediator libraries of this type, the coding sequence of which is incorporated into the correct reading frame and in the correct orientation, can produce fusion proteins. For example, Xgt11 will produce fusion proteins whose amino terminus will consist of β-galactosidase amino acid sequences, and whose carboxy termini will consist of a foreign polypeptide. The antigenic epitopes of the subject H. pylori polypeptide can then be detected by antibodies, such as, for example, by reaction with nitrocellulose filters taken from infected plates with anti- / 7. pylori with polypeptide antibodies. The phages captured in this way can then be isolated from the infected plates. Thus, the presence of H. pylori gene homologs can be detected and cloned from other species, and alternative isoforms (including splice variants) can be detected and cloned.

VIII. Kits comprising the nucleic acids, polypeptides or antibodies of the invention

The nucleic acid, polypeptides and antibodies of the invention may be combined with other reagents and kit articles. Kits for diagnostic purposes typically contain nucleic acid, polypeptides or antibodies in vials or other suitable containers The kits typically contain other reagents to carry out hybridization reactions, to polymerase chain reaction (PCR), or to reconstitute lyophilized components such as aqueous media Kits may also contain sample processing agents such as detergents, chaotropic salts, etc. The kits may also contain immobilizing agents such as particles, carriers, wells, scoops and the like. means such as dyes, development agents, radioisotopes, fluorescent agents, luminescent or chemiluminescent agents, enzymes, intercalating agents, etc. By utilizing the nucleic acid sequence information provided herein, one of ordinary skill in the art can readily remain within the skill of the art. Kits may further include instructions for use.

IX. Methods of drug screening using H. pylori polypeptides

By making available purified and recombinant H. pylori polypeptides, the present invention provides methods that can be used to screen for drugs that are either agonists or antagonists of normal cellular function, in this case, the subject H. pylori polypeptides, or for determining their role in intracellular signaling. Such inhibitors or activators may be useful as novel therapeutic agents for the control of H. pylori infections in humans. Various types of assays will be appropriate and are known to those skilled in the art in accordance with the present invention.

In many drug discovery programs that test libraries of compounds and natural extracts, highly efficient methods for obtaining the maximum number of compounds within a given time range are described. Methods that are performed in cell-free systems, which may be derived from, for example, purified or semi-purified proteins, are often referred to as primary screening because they can be designed to allow the development and relatively easy detection of changes in the molecular target that is mediated test compound. Moreover, in the in vitro system, the effects of cellular toxicity and / or bioavailability of the test compound can be substantially ignored. Instead, the method is primarily directed to the effect of the drug on the molecular target, which may be manifested by a change in the binding affinity to other proteins or a change in the enzymatic properties of the molecular target. Accordingly, in an exemplary screening method of the present invention, the target compound is contacted with an isolated and purified H. pylori polypeptide.

Screening assays can be constructed in vitro with purified H. pylori polypeptide or a fragment thereof, such as H. polypeptide.

pylori having enzymatic activity, for example, the ability to form a detectable reaction product. The efficacy of the compound can be evaluated by generating dose response curves from data obtained using various concentrations of the test compound. In addition, a control test can be performed to provide a basis for comparison. Suitable products include those having different, for example, absorbent, fluorescent or chemiluminescent properties, since detection can be simply automated. Various synthetic or naturally occurring compounds can be tested by a procedure to identify those that inhibit or ameliorate H. pylori polypeptide activity. Some of these active compounds may, directly or after chemical changes, promote membrane permeability or solubility, they may also inhibit or improve certain activity (e.g., enzymatic activity) in whole living H. pylori cells.

DETAILED DESCRIPTION OF THE INVENTION

The present invention will be further illustrated by the following examples, which should not be construed as limiting. The contents of all references and published patent applications cited herein are incorporated herein by reference.

I. Cloning and DNA Sequencing of H. pylori

H. pylori chromosomal DNA was isolated according to the basic DNA protocol of Schleif R. F. and Wensink P. C., Practical Methods in Molecular Biology, p. 98, Springer-Verlag, NY., 1981, with minimal modifications. Briefly, cells were pelleted, resuspended in TE (10 mM Tris, 1 mM EDTA, pH 7.6) and GES lysis buffer (5.1 M guanidium thiocyanate, 0.1 M EDTA, pH 8.0, was added). 0.5% N-lauryl sarcosine). The suspension was cooled and ammonium acetate (NH 4 AC) was added to a final concentration of 2.0 M. DNA was extracted, first with chloroform, then phenol-chloroform, and re-extracted with chloroform. DNA was precipitated with isopropanol, washed twice with 70% EtOH, dried and resuspended in TE.

After isolation, total genomic H. pylori DNA was dispersed (Bodenteich et al., Automated DNA Sequencing and Analysis (J.C. Venter, ed.), Academic Press,

1994) to an average size of 2000 bp. After dispersion, the DNA was concentrated and resolved on a standard 1% agarose gel. Several fractions corresponding to approximate sizes of 900-1300 bp, 1300-1700 bp, 1700-2200 bp, 2200-2700 bp, were excised from the gel and purified by the GeneClean procedure (Bio101, Inc.).

The purified DNA fragment was then blunt-ended using T4 DNA polymerase. The treated DNA was then ligated with unique BstXI-linker adapters in a 100-1000 fold molar excess. These vectors are complementary to the BstXI-cut pMPX vectors, while the overflowing ends are not complementary to each other. Thus, linkers will not form concatamers, nor will the cleaved vector easily back-ligate with itself. Linker-treated inserts were separated from unincorporated linkers in a 1% agarose gel and were purified using GeneClean. Linker-modified inserts were then ligated into each of the 20 pMPX vectors to construct a series of shotgun subclone libraries. The vectors contain the lacZ gene outside the reading frame at the cloning site that reaches the reading frame when the adapter-dimer is cloned, allowing blue staining to be obtained.

All further steps are based on the multiplex DNA sequencing protocols set forth in Church G. M. and Kiefler-Higgins S., Science 240: 185188, 1988. Only major modifications of the protocols are highlighted. Briefly, each of the 20 vectors was then transformed into DH5α competent cells (Gibco / BRL, DH5α transformation protocol). Libraries were evaluated by plating on antibiotic plates containing ampicillin, methicillin and IPTG / Xgal. Plates were incubated overnight at 37 ° C. Successful transformants were then placed on plates and collected in multiple stocks. Clones were tapped into 40 ml cultures of growth medium. Cultures were grown overnight at 37 ° C. DNA was purified using Qiagen Midi-prep kits and Tip-100 columns (Qiagen, Inc.). In this way, 100 mg of DNA per stock was obtained. Fifteen 96-well DNA plates were created to obtain 5-10 fold sequence dilutions assuming a 250-300 basis average length.

These purified DNA samples were then sequenced using multiplex DNA sequencing based on chemical degradation methods (Church).

G. M. and Kieffer-Higgins S., Science 240: 185-188, 1988) or Sequithre (Epicenter Technologies) by dideoxy sequencing procedures. The sequencing reaction mixtures were subjected to electrophoresis and transferred to nylon membranes by direct transfer of 40 cm gel electrophoresis (Richterich P. and Church G. M., Methods in Enzymology 218: 187-222, 1993) or by electroblotting (Church, supra). 24 samples were run on one gel. 45 positive membranes were generated by chemical sequencing and 8 dideoxy sequencing. DNA was covalently bound to membranes by exposure to ultraviolet radiation and the DNA hybridized to labeled oligonucleotides complementary to vector tag sequences (Church, supra). The membranes were washed to wash non-specific bound probes and were exposed to X-ray film to visualize the individual sequence ladders. After autoradiography, the hybridized probe was removed by incubation at 65 ° C and the hybridization cycle was repeated with another tag sequence until the membrane was probed 38 times for chemical sequencing membranes and 10 times for dideoxy sequencing membranes. Thus, a large number of films were made from each gel, each containing new sequence information. Whenever a new blot was processed, it was always first probed with an internal standard sequence that was added to each pool.

Digital film images were generated using a laser scanning densitometer (Molecular Dynamics, Sunnyvale, CA). Digitized images were processed on computer workstations (VaxStation 4000’s) using REPLICA ™ (Church et al., Automated DNA Sequencing and Analysis (J.C. Venter, ed.), Academic Press, 1994). Image processing included straightening the lines, adjusting the contrast to equalize the intensity differences, and enhancing the resolution through multiple gaus deconvolution. The sequences were then automatically selected in REPLICA ™ and subjected to an interactive screen read before they were stored in the project database. The screen read was performed by rapid visual scanning of the film image, followed by a mouse click on the bands in the displayed image to modify the base records. Many sequence errors could be detected and corrected because multiple sequence readings covering the same portion of genomic DNA provide adequate sequence excess for editing.

An identification number (corresponding to the microtiter plate, probe information and kit number) was automatically assigned to each sequence. This number serves as a permanent sequence identifier, so it is always possible to identify the origin of any particular sequence without returning to a specialized database.

Routine assembly of H. pylori sequences was performed using the FALCON program (Church, Church et al., Automated DNA Sequence and Analysis (J.C. Venter, ed.), Academic Press, 1994). It has been verified that this program is fast and reliable for most sequences. Assembled contigs were displayed using a modified version of GelAssemble, developed by Genetics Computer Group (GCG) (Devereux et al., Nucleic Acid Res. 12: 387-95, 1984), which interacts with REPLICA ™. This has provided an integrated editor that allows multiple sequential gels images to be immediately retrieved from the REPLICA ™ database and displayed, allowing rapid contig scanning and gel-scan readings when there is a discrepancy between different sequential records in the assembly.

II. Identification, kioning and expression of recombinant H. pylori DNA sequences

In order to facilitate the kioning, expression and purification of membrane and secreted proteins from H. pylori, a strong pET gene expression system (Novagen) was selected for the cation and expression of recombinant proteins in E. coli. To facilitate the purification of recombinant protein products, a DNA sequence encoding a peptide tag, His tag, was also fused to the 3 'end of the DNA of the target sequence. The 3 'end was selected for fusion to avoid altering any 5' terminal signal sequence. An exception to the above was ppiB, a gene cloned for use as a control in expression assays. In this assay, the H. pylori ppiB sequence contains a DNA sequence encoding a His tag fused to the 5 'end of the entire gene because the protein product of this gene does not contain a signal sequence and is expressed as a cytoplasmic protein.

PCR amplification and cloning of DNA sequences containing ORF membrane and secreted proteins from Helicobacter pylori J99 strain

Selected sequences (from the DNA sequence listing of the invention) for cloning from the H. pylori J99 strain were prepared by amplification cloning by polymerase chain reaction (PCR). Synthetic oligonucleotide primers (Table 3) specific for the 5 'and 3' ends of the open reading frames (ORFs) were designed and purchased (GibcoBRL Life Technologies, Gaithersburg, MD, USA). All forward primers (specific for the 5 'end of the sequence) were designed to include an NcoI cloning site at the very 5' end, except for HpSeq. 4821082 where Ndel. These primers were designed to allow initiation of protein transcription at a methionine residue followed by a valine residue and the coding sequence of the remaining native H. pylori DNA sequence. The exception is the H. pylori sequence 4821082, where the initiator methionine is immediately followed by the remainder of the native H. pylori DNA sequence. All reverse primers (specific for the 3 'end of any H. pylori ORF) contained an EcoRI site at the very 5' end, allowing each H. pylori sequence to be cloned into the pET-28b reading frame. The pET-28b vector provides a sequence encoding an additional 20 carboxyterminal amino acids (only 19 amino acids at HpSeq. 26380318 and HpSeq. 14640637) including the 6 histidine residues (at the full C-terminus) that form the His-tag. Except as noted above, the vector is constructed for the ppiB gene. The synthetic oligonucleotide primer specific for the 5 * end of the ppiB gene encoded a BamHI site at its full 5 'end, and the primer for the 3' end of the ppiB gene encoded an Xhol site at its full 5 * end.

Table 3

Oligonucleotide primers used for PCR amplification of H. pylori DNA sequences

Outer membrane proteins Direct primer 5 5 to 3 ' Reverse Primer 5 'to 3'

Outer membrane proteins Direct primer 5 až to 3 ’ Reverse primer 5 'to 3' Protein 16225006 5-TATACCATGGTGGG 5-ATGAATTCGAGTA CGCTAA-3 '(SEQ ID NO: 195) AGGATTTTTG-3 * (SEQ ID NO: 196) Protein 26054702 5 'TTAACCATGGTGA 5 'TAGAATTCGCATA AAAGCGATA-3 ' (SEQ ID NO: 197) ACGATCAATC-3 '(SEQ ID NO: 198) Protein 7116626 5 'ATATCCATGGTGA 5 'ATGAATTCAATTT GTTTGATGA-3 ' (SEQ ID NO: 199) TTTATTTTGCCA-3 ’(Seq. 200) Protein 29479681 5 'AATTCCATGGTGG 5 'ATGAATTCTCGAT GGGCTATG-3 ' (SEQ ID NO: 201) AGCCAAAATC-3 '(SEQ ID NO: 202) I Protein 14640637 5 'AATTCCATGGTG 5 'AAGAATTCTCTA CATAACTTCCATT-3 '(SEQ ID NO: 203) GCATCCAAATGGA-3 '(SEQ ID NO: 204) Periplasmic / secreted proteins Protein 30100332 5 'ATTTCCATGGTCATG 5 'ATGAATTCCATC TCTCATATT-3 ' (SEQ ID NO: 205) TTTTATTCCAC-3 '(SEQ ID NO: 206) I Protein 4721061 5 'AACCATGGTGATTT TAAGCATTGAAAG-3 '(SEQ ID NO: 207) 5 'AAGAATTCCAC TCAAAAl 1 111 IAACA G-3 ’(SEQ ID NO: 208) Other surface proteins

Outer membrane proteins Direct primer 5 až to 3 ’ Reverse Primer 5 'to 3' Protein 4821082 5 'GATCATCCATATGTT 5 'TGAATTCAACCA ATCTTCTAAT-3 '(SEQ ID NO: 209) TTTTAACCCTG-3 '(SEQ ID NO: 210) Protein 978477 5-TATACCATGGTGAA 5-AGAATTCAATT ATTTT ľCTTTTA-3 ’(SEQ ID NO: 211) GCGTCTTGTAAAAG-3 '(Seq. 212) Inner membrane protein Protein 26380318 5-TATACCATGGTGAT 5 'ATGAATTCCCACTT GGACAAACTC-3 '(SEQ ID NO: 213) GGGGCGATA-3 '(Seq. 214) cytoplasmic protein ppi 5 'TTATGGATCCAAAC 5 'TATCTCGAGTTATA CAATTAAAACT-3 '(SEQ ID NO: 215) GAGAAGGGC-3 '(SEQ ID NO: 216)

Genomic DNA prepared from H. pylori J99 strain (ATCC No. 55679; deposited with Genome Therapeutics Corporation, 100 Beaver Street, Waitham, MA 02154) was used as a template DNA source for PCR amplification reactions (Current Protocols in Molecular Biophogs, John Wiley and Sons, Inc., F. Ausubel et al., Eds., 1994). To amplify the DNA sequence containing the H. pylori ORF, genomic DNA (50 nanograms) was placed in a reaction vessel containing 2 mM MgCl2, 1 micromolar synthetic oligonucleotide primers (forward and reverse primers) complementary to and flanking the H. pylori ORF, 0.2 mM from each triphosphate deoxynucleotide; dATP, dGTP, dCTP, dTTP and 2.5 units of thermostable DNA polymerase (Amplitaq, Roche Molecular

Systems, Inc., Branchburg, NJ, USA) to a final volume of 100 microliters. The following thermal cycling conditions were used to obtain DNA amplified products; Perkin Elmer Cetus / GeneAmp PCR System 9600 thermal cycling was used for each ORF:

Protein 26054702, Protein 7116626, Protein 29479681, Protein 30100332, and Protein 4821082;

Denaturation at 94 ° C - 2 min, cycles at 94 ° C-15 sec, 30 ° C -15 sec 72 ° C -1.5 min 23 cycles at 94 ° C -15 sec, 55 ° C -15 sec 72 ° C -1.5 min Reactions were terminated at 72 ° C - 6 min.

Protein 16225006;

Denaturation at 94 ° C - 2 min, cycles at 95 ° C -15 sec, 55 ° C -15 sec and 72 ° C -1.5 min

The reaction was complete at 72 ° C for 6 minutes.

Protein 4721061;

Denaturation at 94 ° C - 2 min, cycles at 94 ° C -15 sec, 36 ° C -15 sec 72 ° C -1.5 min cycles at 94 ° C -15 sec, 60 ° C -15 sec 72 ° C -1.5 min

Reactions were terminated at 72 ° C for 6 minutes.

Protein 26380318;

Denaturation at 94 ° C - 2 min, cycles at 94 ° C -15 sec, 38 ° C -15 sec 72 ° C -1.5 min cycles at 94 ° C -15 sec, 62 ° C -15 sec 72 ° C -1.5 min

Reactions were terminated at 72 ° C for 6 minutes.

Protein 14640637;

Denaturation at 94 "C - 2 min, 94 cycles at -15 ^and C s, 33 ° C for 72 -15 ^E C -1.5 min 94 cycles at -15 DEG C. in 55 DEG C. -15 DEG C. for 72 -1.5 min

Reactions were terminated at 72 ° C for 6 minutes.

H. pylori ppiB amplification conditions;

Denaturation at 94 ° C - 2 min, cycles at 94 ° C -15 s, 32 ° C -15 with 72 C -1.5 min cycles at 94 ° C - 15 s, 56 ° C -15 with 72 ° C - 1.5 min

Reactions were terminated at 72 ° C for 6 minutes

After completion of the thermal cycling reactions, each amplified DNA sample was washed and purified using a Qiaquick Spin PCR purification kit (Qiagen, Gaithersburg, MD, USA). All amplified DNA samples were digested with restriction endonucleases, NcoI and EcoRI (New England BioLabs, Beverly, MA), or in the case of HpSeq. 4821082 (SEQ ID NO: 1309), with NdeI and EcoRI (Current Protocols in Molecular Biology, John Wiley & Sons, Inc., F. Ausubel et al., Eds., 1994). DNA samples were electrophoresed on a 1.0% NuSeive (FMC BioProducts, Rockland, ME USA) agarose gel. DNA was visualized by exposure to ethidium bromide and high wavelength UV radiation. DNA contained in the bands isolated from the agarose gel was purified using the Bio 101 GeneClean Kit protocol (Bio 101 Vista, CA, USA).

Cloning of H. pylori DNA sequences into the prokaryotic expression vector pET28b

The pET-28b vector was prepared for cloning by digesting with NcoI and EcoRI, or for H. pylori protein 4821082 with NdeI and EcoRI (Current Protocols in Molecular Biology, John Wiley & Sons, Inc., F. Ausubel et al.) (1994). For ppiB cioning, a pET-28a vector was used that encodes a His tag so that it can be fused to the 5 'end of the inserted gene, and the cloning site for cloning the ppiB gene was prepared by digestion with BamHI and XhoI restriction endonucleases.

After cleavage, the DNA inserts were cioned (Current Protocols in Molecular Biology, John Wiley & Sons, Inc., F. Ausubel et al., Eds., 1994) into the previously cleaved pET-28b expression vector, except for the amplified ppiB insert, which was cloned into the pET-28a expression vector. The ligation reaction products were then used to transform BL21 of E. coli strain (Current Protocols in Molecular Biology, John Wiley & Sons, Inc., F. Ausubel et al., Eds., 1994) as described below.

Transformation of competent bacteria with recombinant plasmids

Competent bacteria, strain E coliBL2A or strain E. coli BL21 (DE3), were transformed by recombinant pET expression plasmids carrying the cloned H. pylori sequences (Current Protocols in Molecular, John Wiley & Sons, Inc., F. Ausubel et al. (1994). Briefly, 1 microliter of the ligation reaction was mixed with 50 microliters of electrocompetent cells and were subjected to a high voltage pulse, after which the samples were incubated in 0.45 milliliters of SOC medium (0.5% yeast extract, 2.0% tryptone, 10 mM NaCl). , 2.5 mM KCl, 10 mM MgCl ₂ , 10 mM MgSO _4, and 20 mM glucose) at 37 ° C with stirring for 1 hour. The samples were then plated on LB agar plates containing 25 micrograms / ml kanamycin sulfate, where they were grown overnight. Transformed BL21 colonies were tapped and analyzed for evaluation of cloned inserts as described below.

Identification of recombinant pET expression plasmids carrying H. pylori sequences

Individually BL21 transformed with recombinant pET-28b-H. pylori ORFs were analyzed by PCR amplification of cloned inserts using the same forward and reverse primers specific for each H. pylori sequence that were used in the original PCR amplification cloning reactions. Successful amplification confirmed the integration of H. pylori sequences into the expression vector (Current Protocols in Molecular Biology, John Wiley & Sons, Inc., F. Ausubel et al., Eds., 1994).

Isolation and preparation of plasmid DNA from BL21 transformants

Individual clones of recombinant pET-28b vectors carrying properly cloned H. pylori ORFs were harvested and incubated in 5 ml LB medium with 25 micrograms / ml kanamycin sulfate overnight. The next day plasmid DNA was isolated and purified using the Qiagen plasmid purification protocol (Qiagen Inc., Chatsworth, CA, USA).

Expression of recombinant H. pylori sequences in an E. coli pET vector can be propagated in any E. coli K-12 strain e.g. HMS174, HB101, JM109, DH5, and the like, to ionize or prepare the plasmid. Expression hosts include E. coli strains containing a chromosomal copy of the T7 RNA polymerase gene. These hosts are the lysogens of bacteriophage DE3, a lambda derivative that carries the lacI gene, the lacUV5 promoter, and the T7 RNA polymerase gene. T7 RNA polymerase is induced by addition of isopropyl-β-Dtiogalactoside (IPTG), and T7 RNA polymerase transcribes any target plasmid, such as pET-28b, carrying the T7 promoter and target gene. The strains used include: BL21 (DE3) (Studier, F.W., Rosenberg, A.H., Dunn, J.J., and Dubendorff, J.W. (1990) Meth. Enzymol. 185, 60-89).

In order to express recombinant H. pylori sequences, 50 nanograms of plasmid DNA isolated as described above were used to transform competent BL21 (DE3) bacteria as described above (provided by Novagen as part of the kit for the pET expression system). The LacZ gene (βgalactosidase) was expressed in the pET-System as described for recombinant H. pylori constructs. The transformed cells were cultured in SOC medium for 1 hour, and the culture was then plated on LB plates containing 25 micrograms / ml kanamycin sulfate. On the next day, bacterial colonies were harvested and grown in LB medium containing kanamycin sulphate (25 micrograms / ml) to an optical density at 600 nM equal to 0.5 to 1.0 O.D. units. At this point, 1 millimolar IPTG was delivered to the culture for 3 hours to induce gene expression of recombinant H. pylori DNA constructs.

After induction of gene expression with IPTG, the bacteria were settled by centrifugation in a Sorvall RC-3B centrifuge at 3500 x g for 15 minutes at 4 ° C. The pellets were suspended in 50 ml of cooled 10 mM Tris-HCl, pH 8.0, 0.1 M NaCl and 0.1 mM EDTA (STE buffer). Cells were then centrifuged at 2000 x g for min at 4 ° C. The wet pellets were weighed and frozen at -80 ° C until ready for protein purification.

III. Purification of recombinant proteins from E. coli

Analytical methods

Concentrations of purified protein preparations were quantified spectrophotometrically using an absorption coefficient calculated from the amino acid content (Perkins, S.J. 1986 Eur. J. Biochem. 157, 169-180). Protein concentrations were also measured according to the method of Bradford, M. M. (1976) Anal. Biochem. 72, 248-254, and Lowry, O.H., Rosebrough, N., Farr, A.L. & Randall, R.J. (1951) J. Biol. Chem. 193, pages 265-275, using bovine serum albumin as standard.

SDS-polyacrylamide gels (12% or gels with 4.0-25% acrylamide gradient) were purchased from BioRad (Hercules, CA, USA), and were stained with Coomassie Blue. Molecular weight markers included rabbit skeletal muscle myosin (200 kDa), E. coli β-galactosidase (116 kDa), rabbit muscle phosphorylase B (97.4 kDa), bovine serum albumin (66.2 kDa), ovalbumin (45 kDa) ), bovine carbon anhydrase (31 kDa), soybean trypsin inhibitor (21.5 kDa), egg white lysozyme (14.4 kDa) and bovine aprotinin (6.5 kDa).

Purification of soluble proteins

All steps were performed at 4 ° C. The frozen cells were thawed, resuspended in 5 volumes of lysis buffer (20 mM Tris, pH 7.9, 0.5 M NaCl, 5 mM imidazole with 10% glycerol, 0.1% 2-mercaptoethanol, 200 mg / ml lysozyme, 1 mM phenylmethylsulfonyl fluoride (PMSF), and 10 gg / ml of each of leupeptin, aprotinin, pepstatin, L-1-chloro-3- [4-tosylamido] -7-amino-2-heptanone (TLCK), L1-chloro- 3- [4-tosylamido] -4-phenyl-2-butanone (TPCK) and soybean trypsin inhibitor), and were crushed by several passes through a small volume microfluidizer (Model M-110S, Microfluidics International Corporation, Newton, MA). The resulting 0.1% Brij 35 homogenate was produced and centrifuged at 100,000 x g for 1 hour to obtain pure supernatant (crude extract).

After filtration through a 0.8 mm Super filter (Gelman Sciences, FRG), the crude extract was applied directly to Ni ²⁺ -nitrilotriacetate-agarose (NTA) with a 5 ml loading volume (Hochuli, E., Dbeli, H., and Schacheer, A. (1987) J. Chromatography 411, 177-184), which was pre-equilibrated in a lysis buffer containing 10% glycerol, 0.1% Brij 35 and 1 mM PMSF. The column was washed with 250 ml (50 loading volumes) of lysis buffer containing 10% glycerol, 0.1% Brij 35, and was eluted by the following steps: lysis buffer containing 10% glycerol, 0.05% Brij 35, 1 mM PMSF, and sequentially 20, 100, 200, and 500 mM imidazole. Fractions were monitored by absorbance at OD 280 nm, and peak fractions were analyzed by SDS-PAGE. Fractions containing the recombinant protein were eluted at 100 mM imidazole.

Recombinant 14640637 and β-galactosidase (IacZ) and peptidylprolyl cis-trans isomerase (ppiB) proteins

Fractions containing recombinant proteins from Ni ²⁺ -NTA-agarose columns were collected and concentrated to approximately 5 ml by centrifugation filtration (Centriprep-10, Amicon, MA), and directly loaded onto a 180-ml column (1.6 x 91 cm) with Sephacryl S-100 HR gel filter medium equilibrated in Buffer A (10 mM Hepes, pH 7.5, 150 mM NaCl, 0.1 mM EGTA) and run in Buffer A at 18 ml / h. Fractions containing the recombinant protein were identified by absorbance at 280 nm and analyzed for SDS-PAGE. Fractions were collected and concentrated by centrifugation filtration.

Recombinant protein 7116626

Fractions containing recombinant protein from Ni ²⁺ -NTA-agarose column were collected and dialyzed overnight against 1 liter of dialysis buffer (10 mM MOPS, pH 6.5, 50 mM NaCl, 0.1 mM EGTA, 0.02%). Brij 35 and 1 mM PMSF). In the morning, the white precipitate was removed by centrifugation and the resulting supernatant was applied to 8 ml (8 x 75 mm) MonoS high performance liquid chromatography column (Pharmacia Biotechnology, Inc., Piscataway, NJ, USA) equilibrated in Buffer B (10 mM MOPS, pH 6). , 5, 0.1 mM EGTA) containing 50 mM NaCl. The column was washed with 10 loading volumes of Buffer B containing 50 mM NaCl, and developed with a 50 mL linear gradient of increasing NaCl (50-500 mM). Recombinant protein 7116626 eluted as a sharp peak at 300 mM NaCl.

2. Purification of insoluble proteins from inclusion bodies

The following steps were performed at 4 ° C. Cell pellets were suspended in lysis buffer with 10% glycerol, 200 mg / ml lysozyme, 5 mM EDTA, 1 mM PMSF and 0.1% mercaptoethanol. After passing through a cell disrupter, the resulting homogenate was mixed with 0.2% deoxychophate for 10 minutes, then centrifuged at 20,000 x g for 30 minutes. The pellets were washed with lysis buffer containing 10% glycerol, 10 mM EDTA, 1% Triton X-100, 1 mM PMSF and 0.1% mercaptoethanol, followed by several washes with lysis buffer containing 1 M urea, 1 mM PMSF and 0. 1% 2-mercaptoethanol. The resulting white pellet consisted primarily of inclusion bodies without unbroken cells and membrane material.

Recombinant proteins 26054702,16225006, 30100332,4721061

The following steps were carried out at room temperature. The purified inclusion bodies were dissolved in 20 ml of 8.0 M urea in lysis buffer with 1 mM PMSF and 0.1% 2-mercaptoethanol and incubated at room temperature for 1 hour. Materials that did not dissolve were removed by centrifugation. The clean supernatant was filtered and then loaded onto a Ni ²⁺ -NTA agarose column pre-equilibrated in 8.0 M urea in lysis buffer. The column was washed with 250 mL (50 loading volumes) of lysis buffer containing 8 M urea, 1.0 mM PMSF and 0.1% 2-mercaptoethanol and developed by subsequent steps of lysis buffer containing 8 M urea, 1 mM PMSF, 0, 1% 2-mercaptoethanol and sequentially 20, 100, 200, and 500 mM imidazole. Fractions were monitored by absorbance at OD ₂ bo nm and the peak fractions were analyzed

100 on SDS-PAGE. Fractions containing the recombinant protein were eluted at 100 mM imidazole.

Recombinant proteins 29479681,26380318

The pellet containing inclusion bodies was dissolved in buffer B containing 8 M urea, 1 mM PMSF and 0.1% 2-mercaptoethanol, and incubated for 1 hour at room temperature. Insoluble materials were removed by centrifugation at 20,000 xg for 30 min and the purified supernatant was loaded onto a 15 ml (1.6 x 7.5 cm) SP-Sepharose column pre-equilibrated in B buffer, 6 M urea, 1 mM PMSF, 0.1% 2-mercaptoethanol. After washing with 10 loading volumes, the column was developed with a linear gradient from 0 to 500 mM NaCl.

Dialysis and concentration of protein samples

Urea was slowly removed from the protein samples by dialysis against Tris-buffered saline (TBS; 10 mM Tris pH 8.0, 150 mM NaCl) containing 0.5% deoxycholate (DOC) with gradually decreasing urea concentration, as follows: 6 M, 4 M, 3 M, 2 M, 1 M, 0.5 M and finally TBS without urea. Each dialysis step was carried out for at least 4 hours at room temperature.

After dialysis, samples were concentrated by pressure filtration using Amicon stirred cells. Protein concentrations were measured using the methods of Perkins (1986 Eur. J. Biochem. 157, 169-180), Bradford ((1976) Anal. Biochem. 72, 248-254) and Lowry ((1951) J. Biol. Chem. 193, pages 265-275).

Recombinant proteins purified by the methods described above are summarized in Table 4 below.

101

Table 4

J99 identified. sequence homologue caller ID. protředí. BLAST genic symbol homoló- ga Bakt. cells. the fraction used for recombinant purification. protein process purification relative mol. % by weight on an SDSPAGE gel Konečná kone. by purification. protein composition buffer solution of

External membrane proteins

I 116225006 P28635 YEAC inclusion bodies His-tag 18 kDa 5 mg / ml B I26054702 P15929 flgH inclusion bodies His-tag 37 kDa 1.18 mg / ml B - dry pellets Iľ116626 P26093 e (P4) soluble faction His-tag 29 kDa 0.8 mg / ml A 1.85 mg / ml C I2947968I P13036 fecA inclusion bodies SP- Sepharose 23 kDa 2.36 mg / ml B 0.5 mg ml B - than dry pellets 14640637 P16665 TPF1 soluble faction His-tag 17 kDa 2.4 mg / ml A gel filtration S100 HR

Periplasmic / secreted proteins

102

3010032 P23847 dppA inclusion bodies His-tag 11 kDa 2.88 mg / ml ^B 4721061 P36175 GCP inclusion bodies His-tag 38 kDa 2.8 mg / ml B

Other surface proteins

4821082 P08089 M protein inclusion bodies His-tag 20 kOa 1.16 mg / ml B 978477 L28919 FBP54 inclusion bodies SP- Sepharose 44 kDa 2.56 mg / ml B 0.3 mg / ml B

Internal membrane proteins

26380318 P15933 Fligel inclusion bodies SP- Sepharose 11 kDa 22 mg / ml B

J99 homologue genic Bakt. cells. process relative final composition Identified. caller ID. symbol fraction used purification Mol. horses. purif. buffer sequence protředí. BLAST homologue and for recombinant purification. protein Mass on SDSPAGE gel protein solution of

His-tagged control proteins

I P00722 lacZ soluble faction His-tag 116 kDa 10 mg / ml A S200 HR gel filtration ppiB soluble faction His-tag 21 kDa 4.4 mg / ml A gel filtration S100 HR

103

| - composition buffer solutions: A = 10 mM Hepes pH 7.5, 150 mM NaCl, 0.1 mM EGTA B = 10 mM Tris pH 8.0, 150 mM NaCl, 0.5% DOC C = 10 mM MOPS pH 6.5, 300 mM NaCl, 0.1 EGTA

IV. Analysis of H. pylori proteins as vaccine candidates

In order to analyze H. pylori proteins for use in the vaccine formulation of the invention, several H. pylori proteins have been expressed, immunologically characterized and tested in animal efficacy studies as outlined below. Specifically, the immunomodulatory effects of H. pylori proteins were examined in a mouse / H pylori model that mimics human H. pylori infection in humans. In these studies, the effect of oral immunization of selected H. pylori polypeptides in mice infected with H. pylori was determined.

Identification, cloning and expression of recombinant Helicobacter pylori sequences

To facilitate cloning, expression and purification of membrane and / or secreted proteins from H. pylori, the pET gene expression system (Novagen) was selected for cloning and expression of recombinant proteins in Escherichia coli. Further, for proteins having a signal sequence at their amino terminus, a DNA sequence encoding a His-tag was fused to the 5 'end of the interesting H. pylori DNA sequences to facilitate purification of recombinant protein products.

PCR amplification and cloning of ORF-containing DNA sequences for membrane and secreted proteins from Helicobacter pylori J99 strain.

Sequences selected (from the DNA sequence listing of the invention) for cloning from the H. pylori J99 strain were prepared for amplification cloning by polymerase chain reaction (PCR). All selected sequences encode H. pylori outer membrane proteins, with vac9 (SEQ ID NO: 125),

104 vac10 (SEQ ID NO: 147), vac22 (SEQ ID NO: 121) and vac41 (SEQ ID NO: 176) all have a terminal phenylalanine residue. Similarly, vac32 (SEQ ID NO: 108), vac36 (SEQ ID NO: 149), and vac37 (SEQ ID NO: 139) sequences all have a terminal phenylalanine residue and a C-terminal tyrosine cluster. Synthetic oligonucleotide primers for each subject ORF (Table 5) specific for the predicted mature 5 'end of the ORF and downstream (3') of the predicted translation termination codon were designed and purchased (GibcoBRL Life Technologies, Gaithersburg, MD, USA). All forward primers (specific for the 5 'end of the ORF in question) were designed to include a SamIII restriction site followed by an NdeI restriction site. These primers were designed to allow initiation of protein translation at the methionine residue encoding within the NdeI site of restriction site sequence (for non-His tagged recombinant protein production) or fusion of a frame with a His-tag DNA sequence (for production of His tagged recombinant protein), followed by a coding sequence for the remainder of the native H. pylori DNA. All reverse oligonucleotide primers (specific downstream (3 ') from the predicted translation termination codon ORF) were designed to include an EcoRI restriction site at the 5' end. This combination of primers would allow each subject ORF to be cioned into pET28b (to produce a His-tagged recombinant protein) or pET30a (to produce a non-His-tagged or native recombinant protein). The vector pET28b provides a sequence encoding an additional 20 amino-terminal amino acids (plus methionine at the NdeI restriction site) including a region of the six histidine residues that make His tag.

Genomic DNA prepared from H. pylori J99 strain (ATCC 55679) was used as a template DNA source for PCR amplification reactions (Current Protocols in Molecular Biology, John Wiley & Sons, Inc., F. Ausubel et al., Eds., 1994) . To amplify the DNA sequence containing the H. pylori specific ORF, genomic DNA (50 nanograms) was introduced into a reaction tube containing 200 nanograms of both direct and reverse synthetic oligonucleotide primer specific for the ORF in question and 45 microliters purchased by SuperMix PCR (GibcoBRL Life Technologies, Gaithersburg, MD). ) in a total volume of 50 microliters. SuperMix PCR is supplied in concentrations of 1.1 X and contains 22 mM Tris-HCl (pH 8.4), 55 mM KCl, 1.65 mM MgCl 2, 220 micromoles each

105 of the following: dATP, dCTP, dGTP and dTTP, 22 recombinant Taq polymerase / ml units and stabilizers. The following thermal cycling conditions were used to obtain amplified DNA products for each ORF using a Perkin Elmer Cetus / Gene Amp PCR System Thermal Cycler.

Table 5: oligonucleotide primers

gene Direct primer Reverse primer vac9 (nt sequence no. 28) (aa sequence no. 125) CGCGGATCCATATGGCTGAAA AAACGCCTTTTTTTAAAACTAA AAACCAC (SEQ ID NO: 257) CCGGAATTCATCAGTATTCAA TGGGAATAAAGCC (SEQ ID NO: 258) vac10 (nt sequence no. 50) (aa sequence no. 147) CGCGGATCCATATGAAAGAAG AAGAAAAAGAAGAAAAAAAGA CAGAAAGG (SEQ ID NO. 259) CCGGAATTCGCTTAAAAGAAA ATAGTCCCCCAAACGC (SEQ ID NO: 260) Vac22 (nt sequence no. 24) (aa sequence no. 121) CGCCGGATCCATATGAAAGAG GTCATTCCACCCCTTCAACCC C (SEQ ID NO 261) CCGGAATTCATATAAATATCA TATAGGCAGAAAAAC (SEQ ID NO: 262) vac32 (nt sequence no. 11) (aa sequence no. 108) CGCGGATCCATATGGAGGCA GAGCTTGATGAAAAATC (SEQ ID NO: 263) CCGGAATTCGATTGATTTTGT CAAATCTAAAATCCC (SEQ ID NO: 264)

106

vac36 (hop A) (nt sequence no. 52) (aa sequence no. 149) TATTATACATATGGAAGAAGAT GGG (SEQ ID NO: 265) TAATCTCGAGTTTAGAAGGCG TA (SEQ ID NO: 266) vac37 (I-hop) (nt sequence no. 42) (aa sequence no. 139) TTATATTCATATGGAAGACGAT GGC (SEQ ID NO: 267) AATTCTCGAGCCTCTTTATAA GCC (SEQ ID NO: 268) vac41 (nt sequence no. 79) (aa sequence no. 176) CGCGGATCCATATGGTAGAAG CCTTTCAAAAACACCAAAAAGA CGG (SEQ ID NO: 269) CCGGAATTCGGAGCCAATAG GGAGCTAAAGCC (SEQ ID NO: 270)

Sequences for Vac32, Vac9 and Vac22

Denaturation at 94 ° C for 30 s cycles at 94 ° C for 15 s, 55 ° C for 15 s and 72 ° C for 1.5 min Reactions were terminated at 72 ° C for 8 min

Sequences for Vac10 and Vac41

Denaturation at 94 ° C for 30 sec cycles at 94 ° C for 15 sec, 55 ° C for 15 sec and 72 ° C for 2.5 min Reactions were terminated at 72 ° C for 8 min

Sequences for Vac36 and Vac37

Denaturation at 94 'C for 15 sec, 30 ° C for 15 sec and 72 ° C for 1.5 min 23 cycles at 94' C for 15 sec, 55 ° C for 15 sec and 72 'C for 1.5 min

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Reactions were terminated at 72 ° C for 6 minutes

After the thermal cycling reactions were completed, each amplified DNA sample was electrophoresed on 1.0% agarose gels. DNA was visualized by exposure to ethidium bromide and long wave UV radiation and excised in goal slices. DNA was purified using the Wizard PCR Preps Kit (Promega Corp., Madison, WI, USA), and then subjected to digestion with SamHI and EcoRI (Current Protocols in Molecular Biology, John Wiley & Sons, Inc., F. Ausubel et al. , eds., 1994). The digested PCR amplicon was then re-subjected to electrophoresis and purification as before.

Ligation of H. pylori DNA sequences into cloning vectors

The vector pOK12 (J. Vieira and J. Messing, Gene 100: 189-194, 1991) was prepared for cloning by digestion with SamHI and EcoRI for Vac9, 10, 22, 31 and 32, while the vector pSU21 (B. Bartolome et al.). al., Gene 102: 75-78, 1991) was prepared for cloning by digestion with SamHI and EcoRI for Vac 41 (Current Protocols in Molecular Biology, John Wiley & Sons, Inc., F. Ausubel et al., eds., 1994). Vectors were subjected to electrophoresis on 1.0% agarose gels and purified using Wizard Wizard Preps kit (Promega Corp., Madison, WI, USA). After ligation of the purified cleaved vector and the purified cleaved amplified H. pylori ORF, the ligation reaction products were transformed into competent E. coli JM109 cells according to standard methods (Current Protocols in Molecular Biology, John Wiley & Sons, Inc., F. Ausubel et al., Eds). , 1994). Individual bacterial colonies were screened for those containing the correct recombinant plasmids by incubation in LB culture solution overnight (plus 25 µg / ml kanamycin sulfate for pOK12-based plasmids or 25 µg / ml chloramphenicol for pSU21-based plasmids), followed by plasmid DNA preparation using the Magic Minipreps system (Promega Corp., Madison, WI, USA) and then analyzed by restriction digestion (Current Protocols in Molecular Biology, John Wiley & Sons, Inc., F. Ausubel et al., eds., 1994) .

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Cloning of H. pylori DNA sequences into prokaryotic expression vectors pET28b and pET30a

The expression vectors pET28b and pET30a were prepared for cloning by digestion with NdeI and EcoRI (Current Protocols in Molecular Bioogens, John Wiley & Sons, Inc., F. Ausubel et al., Eds., 1994). H. pylori DNA sequences were removed from the plasmid strands pOK12 (Vac9, 10, 23, 31, and 32) or pSU21 (Vac41) by digestion with NdeI and EcoRI (Current Protocols in Molecular Bioiogy, John Wiley & et al., eds., 1994). DNA sequences of pET28b, pET30a, and H. pylori were subjected to electrophoresis on a 1% agarose gel and purified using the Wizard PCR Preps kit (Promega Corp., Madison WI, USA). After ligation of the purified cleaved expression vector and the purified cleaved H. pylori DNA sequences, the ligation reaction products were transformed into competent E. coli JM109 cells (Current Protocols in Molecular Bioogy, John Wiley & Sons, inc., F. Ausubel et al., Eds. , 1994). Individual bacterial colonies were screened for those containing the correct recombinant plasmids by preparing plasmid DNA as described above, followed by restriction digestion analysis and DNA sequencing (Current Protocols in Molecular Bioogy, John Wiley & Sons, Inc., F. Ausubel et al., eds., 1994). These recombinant plasmids were then used to transform specific E. coli expression strains.

Transformation of competent bacteria with recombinant expression plasmids

Competent bacterial strains (BL21 (DE3), BL21 (DE3) pLyS, HMS174 (DE3) and HMS174 (DE3) pLysS) were prepared and transformed with recombinant expression plasmids carrying cloned H. pylori sequences according to standard methods (Current Protocols in Molecular Bioiogy, John) Wiley and Sons, Inc., F. Ausubel et al., Eds., 1994) These expression host strains contain a chromosomal copy of the T7 RNA polymerase gene, these hosts being the bacteriophage DE3 lysogens, a lambda derivative carrying the lacI gene, the lacUV5 promoter. and the T7 RNA polymerase gene The expression of the T7 RNA polymerase is induced by the addition of isopropyl-QD-thiogalactoside (1PTG) and the T7 RNA polymerase then transcribes any target plasmid, for example pET28b, which carries the T7 promoter sequence and the gene of interest.

109

Expression of recombinant H. pylori sequences in E. coli

Transformants were harvested from LB agar plates containing 25 µg / ml kanamycin sulfate (ensuring maintenance of recombinant pET28b-based plasmids) and used to inoculate a culture solution containing 25 µg / ml kanamycin sulfate and cultured to an optical density of 0.5 to 1.0 OD. units at 600 nm, when 1 mM 1PTG was added to the culture for one to three hours to induce gene expression of recombinant H. pylori DNA constructs. After induction of gene expression by 1PTG, the bacteria were pelleted by centrifugation and resuspended in solubilizing buffer SDS-PAGE and subjected to SDS-PAGE (Current Protocols in Molecular Biology, John Wiley & Sons, inc., F. Ausubel et al., Eds. , 1994). Proteins were visualized by Coomassie Brilliant Blue induction or detected by Western immunoblotting using a specific anti-His tagged monoclonal antibody (Clontech, Palo Alto, CA) using standard methods (Current Protocols in Molecular Biology, John Wiley & Sons, Inc.). (F. Ausubel et al., Eds., 1994). The host strain that yielded the highest level of recombinant protein production was then selected for use in large-scale induction to purify the recombinant protein. All of the following proteins were expressed recombinantly and the strain giving the highest levels of expression was recorded: BL21 (DE3) (vac31, vac26, vac37); BL21 (DE3) pLysS (vac 9.32); HMS174 (DE3) (vac 10.11).

Purification of recombinant proteins and generation of specific antisera

Large-scale cultures were seeded and grown as above and induced with 1 mM 1PTG for 3 hours. After induction, the bacteria were pelleted by centrifugation in a Sorvall centrifuge at 3500 x g for 15 min at 4 ° C. All expressed recombinant proteins were present in the insoluble fraction of inclusion bodies. Inclusion bodies were purified according to standard protocols (Antibodies, Cold Spring Harbor Laboratory Press, E. Harlow and D. Lane, eds., 1988). The recombinant protein produced by vac32 was solubilized in 8 M urea and partially purified by nickel chromatography (reference). Denatured recombinant proteins were purified by SDS-PAGE gel electrophoresis and after

By visualizing with Coomassie Brilliant Blue, the protein was excised from the gel and the gel sections were homogenized. This material was used to induce the production of specific polyclonal antibodies in mice or rabbits according to standard protocols (Antibodies, Cold Spring Harbor Laboratory Press, E. Harlow and D. Lane, eds., 1988).

Immunological characterization of recombinant proteins

In all cases of attempts to elicit antibody production, high titer antiserum was generated, confirming the immunogenicity of the recombinant proteins. Furthermore, these specific antisera were used to analyze whether the protein encoded by the cloned gene was expressed in H. pylori. Western Immunoblot analysis using standard protocols (Current Protocols in Molecular Biology, John Wiley & Sons, Inc., F. Ausubel et al., Eds., 1994) confirmed that the H. pylori J99 strain actually expressed the expected molecular weight proteins that reacted santiser vac10, vac32, vac31 and vac36. Specific antiserum was also used to determine the level of antigen conservation among a large number of H. pylori isolates, which were obtained from various geographical locations worldwide and from all types of clinical manifestations including gastritis, duodenal ulcer, gastric ulcer and gastric cancer. It was found that each strain produced a protein that reacted specifically with each antiserum.

Furthermore, H. pylori cells from strains J99, 17874, AH244, and SS1 were fractionated into various cell compartments (Doig and Trust 1994 Infect. Immun. 62: 45264533: O'Toole et al. 1995 J. Bacteriol. 177: 6049-6057) . Specific antiserum was used to probe these fractions with Western Immunobiot to identify the fraction in which the protein was found. In all cases, the immunoreactive protein was present in the outer membrane, as predicted by the sequence properties and by screening the motifs described herein.

111

Demonstration of protein efficacy as a vaccine

Purification of vac36 for efficacy studies

All subsequent steps were performed at 4 ° C. Cell pellets were resuspended in 5 volumes of lysis buffer per gram of cells (50 mM sodium phosphate pH 8.0, 0.5 M NaCl, 5 mM imidazole) with 10 mM EDTA, 1 mM phenylmethylsulfonyl fluoride (PMSF) and 0.1% β mercaptoethanol, and broken by several passes through a small volume microfluidizer (Model M-110S, Microfluidics International Corporation, Newton, MA). The resulting homogenate was prepared with 0.2% sodium deoxycholate (DOC), stirred for 20 minutes and then centrifuged (10,000 g x 30 min). The pellets were washed twice with lysis buffer containing 10 mM EDTA, 1% Triton X-100, 1 mM PMSF and 0.1% β-mercaptoethanol, then with lysis buffer containing 1 M urea, 1 mM PMSF and 0.1% β-mercaptoethanol. The obtained white pellet consists mainly of inclusion bodies without unbroken cells and membrane substances.

The inclusion bodies were dissolved in 20 ml of 6 M guanidine-HCl in lysis buffer with 1 mM PMSF and 0.1% β-mercaptoethanol and incubated on ice for 1 hour. The undissolved substances were removed by centrifugation (100,000 x 30 min.) The clear mother liquor was filtered through a 0.8 µm Supor filter (Gelman Sciences, Germany) and then loaded directly onto a 10 ml Ni ²⁺ - NTA agarose column. (Hochuli et al. 1987) pre-equilibrated in 6M guanidine-HCl in lysis buffer containing 1 mM PMSF and 0.1% β-mercaptoethanol. The column was washed with 20 mL (2 loading volumes) of lysis buffer containing 6 M guanidine HCl, 1 mM PMSF and 0.1% β-mercaptoethanol, then the guanidine-HCl mixture was slowly removed using a 100 mL linear gradient (from 6 M to 0 M) guanidine (HCl) lysis buffer containing 0.5% Brij 35, 1 mM PMSF, 0.1% β-mercaptoethanol. Then the column was developed with a 25 ml linear gradient of increasing concentration of imidazole (5-500 mM) in a lysis buffer containing 0.5% Brij 35, 1 mM PMSF and 0.1% β-mercaptoethanol. Recombinant proteins elute as a peak with a center at 100 mM imidazole.

112

Fractions containing recombinant proteins were pooled, concentrated to approximately 8 mL by centrifuge filtration (Centriprep-10, Amicon, MA) and loaded directly onto a 350 mL column (2.2 x 91 cm) Sephacyl S-100 HR gel filtration medium equilibrated in buffer A (50 mM sodium phosphate, pH 8.0, 500 mM NaCl, 0.1 mM EGTA, 1 mM PMSF, 0.1% β-mercaptoethanol, 0.5% Brij 35), and eluted in buffer A at 30 ml / h. Fractions containing recombinant protein were identified by absorbance at 280 nm and analyzed by SDS-PAGE. Fractions were pooled, concentrated to 1.5-2 mg / mL and dialyzed overnight against 10 mM sodium phosphate pH 7.5, 150 mM NaCl, 0.1 mM EGTA, and 0.5% Brij 35. Protein concentration in the quantial was quantified and then aliquoted before freezing to -20 ° C.

Mouse model of Heticobacter pylori infection

A mouse model of H. pylori infection was obtained by infection of C57BL / 6 mice with an H. pylori Sydney SS1 strain and used to evaluate the efficacy of recombinant H. pylori vac36. This mouse-adapted H. pylori strain is cagA + vacA +, shows colonization levels in C57BL / 6 mice equivalent to those observed in humans, forms adhesion pedestals, colonizes at least 8 months, and induces chronic active gastritis and mucotic atrophy (Lee et al., Gastroenterology, 112: 1386-1397, 1997). Dose response studies showed 100% infection rates in cousins C57BL / 6 and Balb / C at 8 weeks post challenge with a single vaccination with 10® organisms.

Evaluation of H. pylori gastric infection

The presence of H. pylori organisms in gastric tissue was determined by gastric tissue culture and quantitative urease assay. In this second method, a longitudinal segment of anthra representing approximately 1/4 of the total anthral region was placed in 1 ml of urea culture solution. After 4 hours, the extent of color change due to urea hydrolysis and increased pH was quantified by spektr ₅₅₀ spectrophotometric measurement (Fox et al., Immunol. 88: 400-406, 1996). The test sensitivity is ~ 10 ³ H. pylori organisms. Positive (H. pylori infected) gastric tissue was defined as a sample showing 2 standard deviations

113 above the mean A550 value obtained from a group of uninfected uninfected age matched control mice.

Evaluation of local immune response to immunization in gastric tissue

Longitudinal sections of gastric tissue from the esophagus to duodenal region were coated with an OCT coating composition, frozen in liquid nitrogen, and cryosections were immunologically elicited with monoclonal antibodies recognizing CD4 + or CD8 + T cells or anti-mouse IgA antisera to identify Papa-containing IgA (IgACC) et al., Infect. Immun. 63: 12461252, 1995). The degree of local gastric immune response was expressed quantitatively as the number of CD4 * · CD8 * or IgACC cells per mm ^{2 of} gastric area examined.

Protective activity of purified H. pylori vac36 recombinant antigen

The ability of purified H. pylori-derived recombinant vac36 antigen to interfere with the introduction of H. pylori infection was investigated in mice. Groups (n = 10) of 6-8 week old female C57BL / 6 mice were immunized orally 4 times at weekly intervals as follows: 1) 100 µg vac36 recombinant antigen and 10 µg cholera toxin (CT) adjuvant, 2) 1 mg H lysate antigens pylori and 10 µg CT, and 3) 0.2 M bicarbonate buffer and 10 µg CT adjuvant. Mice were challenged 2 weeks later for 3 consecutive days by oral administration of 10 ⁸ H. pylori organisms. The experiment was terminated 2 weeks after challenge and the level of H. pylori infection was evaluated by bacterial colony counts and quantitative urease assays.

Oral immunization with vac36 antigen interfered with the introduction of H. pylori infection in experimental H. pylori infection. Mice immunized with purified recombinant vac36 antigen showed significantly lower levels of H. pylori colonization as assessed by gastric urease activity and bacterial counts (Table 6). Oral immunization with vac36 antigen also resulted in the generation of a local protective gastric immune response. Higher numbers of CD4 + T and IgACC cells were obtained in gastric tissues of mice

114 immunized with vac36 as compared to unimmunized H. pylori-infected mice (Table 7).

Table 6

The recombinant vac36 antigen protects mice from challenge with H. pylori

vaccinated group Urease activity ⁸ P ^b H. pylori® burden p ^b vac36 0.199 ± 0.080 0.0022 55 800112 599 0.0125 H. pylori lysate 0,05710,007 0.0002 2 3601955 0.0002 buffer 1,65510,420 - 131 000118 391 -

and Urease activity is expressed as the mean value of _{5 5} with ± SEM of duplicate antral samples of n = 10 mice / group.

b by Wilcoxon Rank Sum Test compared to mice immunized with CT adjuvant alone c H. pylori levels in gastric tissue were evaluated based on bacterial counts and are reported as mean colonies forming units ± SEM

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Table 7

Vac36-immunized mice generate a local gastric immune response in experimental H. pylori infection

vaccinated group CD4 + CD8 + IgACC vac36 Kardia corpus antrum Kardia corpus antrum Kardia corpus antrum 33 ± 9 ^a 54 ± 8 * 31 ± 8 3 ± 2 0 1 ± 1 24 ± 12 79 ± 16 67 ± 13 LyzátH. pylori 31 ± 13 36 ± 19 24 ± 8 4 ± 2 2 ± 1 2 ± 1 31 ± 9 73 ± 13 * 79 ± 15 buffer 12 ± 2 27 ± 8 18 ± 4 1 ± 1 0 0 4 ± 2 30 ± 13 46 ± 14

^a Mean cell count / mm ^{2 of} gastric area ± SEM p <0.05 according to Wilcoxon Rank Sum Test compared to unimmunized mice infected

H. pylori

V. Sequence analysis of Helicobacter pylori strains genes

Four genes from several H. pylori strains were cloned and sequenced to compare DNA and deduced amino acid sequence. This information was used to determine the sequence variation between the H. pylori J99 strain and other H. pylori strains isolated from human patients.

Preparation of chromosomal DNA

Cultures of H. pylori strains (listed in Table 10) were grown in BLBB (1% Tryptone, 1% peptamine 0.1% glucose, 0.2% yeast extract 0.5% sodium chloride, 5% fetal bovine serum) to 0, 2 at OD ₆₀₀ . Cells were centrifuged in Sorvall RC-3B at 3500 xg at 4 ° C for 15 minutes and the pellet was suspended in 0.95 ml of 10 mM TrisHCl, 0.1 mM EDTA (TE). Lysozyme was added to a final concentration of 1 mg / ml along with SDS to 1% and RNAase A + T1 to 0.5 mg / ml and 5 units / ml, and the reaction mixture was incubated at 37 ° C for one hour. Proteinase K was then added to a final concentration of 0.4 mg / ml and the sample incubated at 55 ° C for more than one hour. NaCl to a concentration of 0.65 M was added to the sample, which was then carefully added

116 was mixed and 0.15 ml of 10% CTAB in 0.7 M NaCl (final 1% CTAB / 70 mM NaCl) was added, followed by incubation at 65 ° C for 20 minutes At this point, samples were extracted with chloroform / isoamyl alcohol, extracted with phenol and extracted again with a mixture of chloroform and isoamyl alcohol. DNA was precipitated with either EtOH (1.5 times volume) or isopropanol (0.6 times volume) at -70 ° C for 10 minutes, washed in 70% EtOH and suspended in TE.

PCR amplification and cloning.

Genomic DNA prepared from twelve Helicobacter pylori strains (Current Protocols in Molecular Biology, John Wiley &amp; Sons, Inc., F. Ausubel et al., Eds., 1994) was used as the template DNA source for the PCR amplification reaction. To amplify the DNA sequence containing the H. pylori ORF, genomic DNA (10 nanograms) was placed in a reaction vessel containing 2 mM MgCl ₂ , 1 micromolar synthetic oligonucleotide primers (forward and reverse primers, see Table 8) complementary to the edges of the H. pylori ORF, 0 2 mM of each of the deoxynucleotide triphosphates; dATP, dGTP, dCTP, dTTP and 0.5 units of thermostable DNA polymerase (Amplitaq, Roche Molecular Systems, Inc., Branchburg, NJ, USA) to a final volume of 20 microliters in duplicate reactions.

Table 8

Oligonucleotide primers used for PCR amplification of H. pylori DNA sequences

I External proteins membrane Direct Primary 5 'to 3' Reverse Primary 5 'to 3' Protein 26054702 5-TTAACCATGGTGAAAA 5 * -TAGAATTCGCCTCTAA (for strains AH4, AH 15, AH61, 5294, 5640, AH18 and AH244) GCGATA-3 * (Seq. 217) AACTTTAG-3 * (SEQ ID NO: 218) Protein 26054702 5 * -TTAACCATGGTGAAAA 5 * -TAGAATTCGCATAA (for strains AH5, 5155, 7958, AH24 and J99) GCGATA-3 * (Seq. 219) CGATCAATC-3 * (SEQ ID NO: 220) Protein 7116626 5 * -ATATCCATGGTGAGTT 5 * -ATGAATTCAATTTT TGATGA-3 '(Seq. 221) TTATTTTGCCA-3 ' (SEQ ID NO: 222)

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I Protein 29479681 5-AATTCCATGGCTATC CAAATCCG-3 '(SEQ ID NO: 223) 5-ATGAATTCGCCAAAA TCGTAGTATT-3 '(SEQ ID NO: 224) Protein 346 5 'GATACCATGGAATTT 5 'TGAATTCGAAAAAGTG ATGAAAAAG-3 '(Seq TAGTTATAC-3 ’(Seq. no. 225) 226)

The following thermal cycling conditions were used to obtain amplified DNA products for each ORF using a Perkin Elmer Cetus / GeneAmp PCR System 9600 thermal cycler:

Protein 7116626 and protein 346;

Denaturation at 94 ° C - 2 min, cycles at 94 ° C -15 sec, 30 ° C -15 sec 72 ° C -1.5 min cycles at 94 ° C -15 sec, 55 ° C at 15 sec 72 ° C -1.5 min

Reactions were terminated at 72 ° C for 6 minutes.

Protein 26054702 for strains AH5, 5155, 7958, AH24 and J99;

Denaturation at 94 ° C for 2 min, cycles at 94 ° C -15 sec, 30 ° C -15 sec 72 ° C -1.5 min cycles at 94 ° C -15 sec, 55 ° C -15 sec 72 ° C - 1.5 min

The reaction was completed at 72 C C - 6 minutes.

Protein 26054702 and protein 294796813 - strains AH4, AH15, AH61, 5294, 5640, AH18aHp244;

Denaturation at 94 C C - 2 min, cycles at 94 C C -15 sec, 30 C C - 20 sec and 72 C - 2 min cycles at 94 C C-15 sec, 55 ’C - 20 sec and 72 C C - 2 min

Reactions completed at 72 C C - 8 minutes.

After completion of the thermal cyclic reactions, each pair of samples was pooled and used directly for cloning into a pCR cloning vector as described below.

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Cloning of H. pylori DNA sequences into pCR TA cloning vector

All amplified inserts were cloned into the pCR 2.1 vector as described in the original TA cloning kit (Invitrogen, San Diego, CA). The ligation reaction products were then used to transform the TOP10F * (INVaF 'for H. pylori sequence 350) strain of E. coli as described below.

Transformation of competent cells by recombinant plasmids

Competent E coli strain TOP10F 'or E. coli strain INVaF' were transformed with recombinant pCR expression plasmids carrying cloned H. pylori sequences according to standard methods (Current Protocols in Molecular Biology, John Wiley &amp; Sons, Inc., F. Ausubel et al. , editors, 1994). Briefly, 2 microliters of 0.5 micromolar BME was added to each tube with 50 microliters of competent cells. Subsequently, 2 microliters of the ligation reaction mixture were admixed to competent cells and incubated on ice for 30 minutes. The cells and ligation mixture were then exposed to a "heat shock" at 42 ° C for 30 seconds and then placed on ice for a further 2 minutes, after which the samples were incubated in 0.45 ml SOC medium (0.5% yeast extract, 2). 0% tryptone, 10 mM NaCl, 2.5 mM KCl, 10 mM MgCl 2, 10 mM MgSO 4, and 20 mM glucose) at 37 ° C with stirring for one hour. Samples were then plated on LB agar plates containing 25 micrograms / ml kanamycin sulfate or 100 micrograms / ml ampicillin and grown overnight. Transformed TOP10F 'or INVaF * colonies were then harvested and analyzed for evaluation of cloned inserts as described below.

Identification of recombinant PCR plasmids carrying H. pylori sequences

Individual TOP10F * or INVaF 'clones transformed with recombinant pCR-Η. pylori ORFs were analyzed by PCR amplification of cloned inserts using the same forward and reverse primers specific for each H. pylori sequence used in the original PCR amplification reactions. Successful amplification confirmed the incorporation of H. pylori sequences into the cloning vector

119 (Current Protocols in Molecular Biology, John Wiley &amp; Sons, inc., F. Ausubel et al., Eds., 1994).

Individual clones of recombinant pCR vectors carrying properly cloned H. pylori ORFs were taken for sequence analysis. Sequence analysis was performed on an ABI sequencer using standard protocols (Perkin Elmer), using vector-specific primers (found in PCRII or pCR2.1, Invitrogen, San Diego, CA), and ORF-specific sequencing primers, which are shown in Table 9. below.

Table 9

The oligonucleotide primers used for sequencing H. pylori DNA sequences

I Proteins In the outside I membranes Direct primers 5 'to 3' Reverse Primers 5 'to 3' protein 26054702 5'CCCTrCATTTTAGAAAT CG-3 '(SEQ ID NO: 227) S’ATTTCAACCAATTCAAT GCG-3 ’(Seq. 228) S’GCCCCTTTTGATTTGAA GCT-3 '(SEQ ID NO: 229) 5’TCGCTCCAAGATACCAA GAAGT-3 '(Seq. 230) 5’CTTGAATTAGGGGCAAA GATCG-3 '(Seq. 231) 5’ATGCGTTTTTACCCAAA GAAGT-3 ’(Seq. 232) 5’ATAACGCCACTTCCTTA TTGGT-3 ’(Seq. 233) 5'CTTTGGGTAAAAACGCAT C-3 '(SEQ ID NO: 234) S’CGATCTTTGATCCTAATTC A-3 '(Sequence # 235) 5'ATCAAGTTGCCTATGCTG A-3 * (SEQ ID NO: 236)

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I Protein 7116626 5’TTGAACACTTTTGATTA TGCGG-3 ’(Seq. 237) 5'GGATTATGCGATTGTTT TACAAG-3 '(SEQ ID NO. 238) S'GTCTTTAGCAAAAATGGC GTC-3 '(SEQ ID NO: 239) 5’AATGAGCGTAAGAGAGCC TTC-3 ’(Sequence # 240) protein 29479681 5'CTTATGGGGGTATTGTC A-3 '(SEQ ID NO: 241) 5'AGGTTGTTGCCTAAAGAC T-3 ’(SEQ ID NO: 243) 5'AGCATGTGGGTATCCA GC-3 '(SEQ ID NO: 242) 5'- CTGCCTCCACCTTTGATC-3 '(SEQ ID NO: 244) Protein 346 5'ACCAATATCAATTGGCA CT-3 '(SEQ ID NO: 245) 5'CTTGCTTGTCATATCTAG C-3 '(SEQ ID NO: 247) 5'ACTTGGAAAAGCTCTGC A-3 * (SEQ ID NO: 246) 5'- GTTGAAGTGTTGGTGCTA-3 '(Seq. 248) 5’CAAGCAAGTGGTTTGG TTTTAG-3 '(Seq. 249) 5'TGGAAAGAGCAAATCAT TGAAG-3 '(Seq. 250) 5'GCCCATAATCAAAAAGCC CAT-3 ´ (sequence δ. 251) 5'CTAAAACCAAACCACTTG CTTGTC-3 '(SEQ ID NO: 252) vector primers 5'- GTAAAACGACGGCCAG-3 '(SEQ ID NO: 253) 5-CAGGAAACAGCTATGAC3 '(SEQ ID NO: 254)

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The results

To determine the amount of PCR errors in these experiments, five individual clones of 26054702 protein prepared from five separate PCR reaction mixtures from a H. pylori J99 strain totaling 897 nucleotides in length were sequenced, after totaling 4485 bases of DNA sequence. The DNA sequence of the five clones was compared to the DNA sequence obtained previously in a different way, i.e. by random shotgun cloning and sequencing. The amount of PCR errors in the experiments described herein was determined to be 2 base changes to 4485 bases, which corresponds to an estimated amount of PCR errors that is less than or equal to 0.04%.

DNA sequence analysis was performed in four different open reading frames, which were identified as genes, and were amplified by PCR methods from twelve different Helicobacter pylori strains. The deduced amino acid sequences of three of the four open reading frames that were selected for review showed statistically significant BLAST homology to defined proteins present in other bacterial strains. These ORFs included: protein 26054702, homologous to val A & B genes encoding the ABC transporter in F. novicida; protein 7116626, homologous to lipoprotein e (P4) present in the outer membrane of H. influenzae; protein 29479681, homologous to fecA, the outer membrane receptor in ferric dicitrate transport in E. coli. Protein 346 was designated as an unknown open reading frame because it showed low homology to sequences in public databases.

To assess the extent of conservation or variation in ORF between different strains of H. pylori, changes in DNA sequences and in deduced protein sequence were compared to DNA and deduced protein sequences found in the H. pylori J99 strain (see Table 10 below). Results are reported as percent identity with H. pylori J99 strain sequenced by random shotgun cloning. To check for any deviations in the J99 sequence, each of the four open reading frames was cloned and sequenced again from the bacterial strain J99 and this sequence information was compared to the sequence information

122 information that was obtained by zinserts cloned by random shotgun sequencing of J99 strain. The data demonstrate that the DNA sequence excursion is in a small range of 0.12% difference (protein 346, strain J99) to about 7% change (protein 26054702, strain AH5). Derived protein sequences either showed no deviation (protein 346, strains AH 18 and AH24) or showed a deviation of 7.66% amino acid changes (protein 26054702, strain AH5).

Table 10

Multiple stem DNA sequence analysis of H. pylori vaccine candidates

J99 Protein No: 2605470 2 260547 02 711662 6 711662 6 2947968 1 294796 81 346 346 length sequenced area: 248 ak. 746 nt 232 ak. 96 nt. 182 ak. 548 nt. 273 ak. 819 nt.

Test strain

identity IF identity NUK. identity IF identity NUK. identity IF identity NUK. identity IF identity NUK. J99 100.00 % 100.00 % 100.00 % 100.00 % 100.00 % 100.00 % 99.63 % 99.88% AH244 95.16% 95,04 % n.d. n.d. 99.09% 96.71% 98.90 % 96.45% H4 95.97% 95,98 % 97,84 % 95.83% n.d. n.d. 97.80 % 95.73% AH5 92.34% 93,03 % 98,28 % 96.12% 98.91% 96.90% 98.53 % 95.73% AH15 95.16% 94,91 % 97.41 % 95.98% 99.82% 97,99% 99.63 % 96.09% AH61 n.d. n.d. 97,84 % 95.98% 99.27% 97.44% n.d. n.d. 5155 n.d. n.d. n.d. n.d. 99.45% 97.08% 98.53 % 95,60% 5294 94.35% 94.37 % 98,28 % 95,40% 99.64% 97.26% 97.07 % 95.48% 7958 94.35% 94.10 % 97,84 % 95,40% n.d. n.d. 99.63 % 96.46%

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5640 95.16% 94.37 % 97.41 % 95.69% 99.09% 97.63% 98.53 % 95.48% AH18 n.d. n.d. 98.71 % 95.69% 99.64% 97.44% 100.00 % 95.97% AH24 94.75% 95,04 % 97,84 % 95,40% 99.27% 96.71% 100.00 % 96.46%

n.d. = not done

VI. Experimental knock-out protocol to identify essential H. pylori genes as potential therapeutic targets

Therapeutic targets have been selected from genes where their protein products appeared to play a key role in essential cellular pathways such as cell envelope synthesis, DNA synthesis, transcription, translation, regulation, and colonization / virulence.

The procedure for deleting portions of H. pylori genes or ORFs and for insertional mutagenesis of the kanamycin resistance cassette has been modified from previously published methods to identify genes that are essential for the cell (Labigne-Roussel et al., 1988, J. Bacteriology 170, p. 1704-1708; Cover et al., 1994, J. Biological Chemistry 269, pp. 10566-10573; Reyrat et al., 1995, Proc. Natl. Acad. Sci. 92, 8768-8772). The result is a gene knock-out.

Identification and cloning of H. pylori gene sequences

The sequences of genes or ORFs (open reading frames) selected as knock-out targets were identified from the genomic sequence of H. pylori and were used to design primers for specific gene / ORF amplification. All synthetic oligonucleotide primers were designed using the OLIGO program (National Biosciences, Inc., Plymouth, MN 55447, USA), and could be purchased from Gibco / BRL Life Technologies (Gaithersburg, MD, USA). If the ORF is less than 800 to 1000 base pairs, the flanking primers are selected from outside the open reading frame.

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Genomic DNA prepared from Helicobacter pylori HpJ99 strain (ATCC 55679; deposited with Genome Therapeutics Corporation, 100 Beaver Street, Waitham, MA 02154) is used as a template DNA source for amplifying ORF by PCR (Polymerase Chain Reaction) (Current Protocols in Molecular Biology, John Wiley &amp; Sons, Inc., F. Ausubel et al., Editor, 1994). For preparation of H. pylori genomic DNA see Example I. PCR amplification is performed by placing 10 nanograms of HpJ99 genomic DNA in a reaction tube containing 10 mM Tris pH 8.3, 50 mM KCl, 2 mM MgCl2, 2 micromolar synthetic oligonucleotide primers (direct = F1 and reverse = R1), 0.2 mM each of deoxynucleotide triphosphates (dATP, dGTP, dCTP, dTTP), and 1.25 units of thermostable DNA polymerase (Amplitaq, Roche Molecular Systems, Inc., Branchburg, NJ, USA) to final volume of 40 microliters. PCR is performed in a Perkin Elmer Cetus / GeneAmp PCR System 9600 Thermal Cycler.

After thermal cycling reactions, each sample of amplified DNA was visualized on a 2% TAE agarose gel stained with ethidium bromide (Current Protocols in Molecular Biology, John Wiley &amp; Sons, Inc., F. Ausubel et al., Editor, 1994) to verify that the reaction results in one product of the expected size. The amplified DNA is then washed and purified using Qiaquick Spin PCR (Qiagen, Gaithersburg, MD, USA).

PCR products were cloned into the pT7Blue T-vector (Catalog No. 69820-1, Novagen, Inc., Madison, WI, USA) using the current protocols in Molecular Biology TA (John Wiley &amp; Sons, Inc., F. Ausubel) et al., eds., 1994). Ligation of the PCR product into the vector is accomplished by mixing a 6-fold molar excess of PCR product, 10 ng of the pT7Blue-T vector (Novagen), 1 microliter of T4 DNA ligase buffer (New England Biolabs, Beverly, MA) and 200 units of T4 DNA ligase. (New England Biolabs) to a final reaction volume of 10 microliters. The ligation was carried out at 16 ° C for 16 hours.

The ligation products were electroporated (Current Protocols in Molecular Biology, John Wiley &amp; Sons, Inc., F. Ausubel et al., Editor, 1994) into XL-1 Blue or DH5-α E. coli electroporation competent cells (Clontech Lab., Inc. Palo

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Alto, CA). In brief ,. 1 microliter of the ligation reaction mixture is mixed with 40 microliters of electrocompetent cells and exposed to a high voltage pulse (25 pF, 2.5 kV, 200 200), and then the samples are incubated in 0.45 ml SOC medium (0.5% yeast extract). , 2.0% tryptone, 10 mM NaCl, 2.5 mM KCl, 10 mM MgCl 2, 10 mM MgSO ₄ and 20 mM glucose) at 37 ° C with stirring for 1 hour. The samples are then plated on LB (10 g / l bacto tryptone, 5 g / l bacto yeast extract, 10 g / l sodium chloride) plates containing 100 microgram / ml ampicillin, 0.3% X-gal, and 100 microgram / ml IPTG. These plates are incubated overnight at 37 ° C. White ampicillin resistant colonies were picked, grown in 5 ml of liquid LB containing 100 micrograms / ml ampicillin, and plasmid DNA was isolated using the Qiagen miniprep protocol (Qiagen, Gaithersburg, MD, USA).

To verify that the correct H. pylori DNA inserts were cloned, these pT7Blue plasmid DNAs are used as templates for PCR amplification of cioned inserts using the same forward and reverse primers that were used to initially amplify the H. pylori J99 sequence. Confirmation that the correct inserts have been cloned is the appearance of the primers and PCR product of the correct size after visualization on a 2% TAE, ethidium bromide labeled agarose gel. Two of the six clones thus verified are collected for each target and frozen at -70 ° C and stored. To minimize errors due to PCR, plasmid DNA is collected from these verified cions and used in the following cloning steps.

These gene / ORF sequences are reused to design a second pair of primers that flank the H. pylori DNA region to be either interrupted or deleted (up to 250 base pairs) within the ORF, but oriented away from each other. Stocks of circular plasmid DNAs from previously isolated clones are used as templates for this round of PCR. Since the amplification orientation of this pair of deletion primers is spaced apart, a portion of the ORF between the primers is not included in the resulting PCR product. The PCR product is a linear piece of DNA with H. pylori DNA at each end and a pT7Blue vector link between them, resulting in a deletion of part of the ORF. The PCR product was visualized on a 1% TAE, ethidium bromide labeled gel to confirm that only one product of the correct size was amplified.

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A kanamycin resistance cassette (LabigneRoussel et al., 1988 J. Bacteriology 170, 1704-1708) was ligated into the PCR product using the previously used TA cloning method (Current Protocols in Moecular Biology, John Wiley &amp; Sons, Inc., F. Ausubel et al. (1994). The kanamycin cassette containing the Campylobacter kanamycin resistance gene is obtained by EcoRI digestion of the recombinant plasmid pCTB8: kan (Cover et al., 1994, J. Biological Chemistry 269, pp. 10566-10573). The correct fragment (1.4 kb) is separated on a 1% TAE gel and isolated using a QIAquick gel extraction kit (Qiagen, Gaithersburg, MD, USA). The ends were repaired using the Klenow Fill Protocol, which included mixing 4 µg of DNA fragment, 1 microliter of dATP, dGTP, dCTP, dTTP at a concentration of 0.5 mM, 2 microliters of Klenow buffer (New England Biolabs) and 5 units of large Klenow fragment. DNA Polymerase I (Klenow) (New England Biolabs) into a 20 microliter reaction mixture, incubated at 30 ° C for 15 min and inactivated enzyme by heating to 75 ° C for 10 min. This blunt-ended kanamycin cassette is then purified through a Qiaquick column (Qiagen, Gaithersburg, MD, USA) to eliminate nucleotides. Then, the "T" overlapping ends are formed by mixing 5 micrograms of kanamycin cassette with blunt ends, 10 mM Tris pH 8.3, 50 mM KCl, 2 mM MgCl ₂ , 5 units of DNA polymerase (Amplitaq, Roche Moiecular Systems, Inc., Branchburg, NJ, USA), 20 microliters of 5 mM dTTP, in 100 microliters of reaction mixture and incubating the reaction mixture for 2 hours at 37 ° C. The "Kan-T" cassette is purified using a QIAquick column (Qiagen, Gaithersburg, MD, USA). The deletion primer PCR product (F2 and R2) is ligated into the Kan-T cassette by mixing 10-25 ng of the deletion primer PCR product, 50-75 ng Kan-T cassette DNA, 1 microliter of 10x T4 DNA figase reaction mixture, 0.5 microliter of T4. DNA ligases (New England Biolabs, Beverly, MA, USA) in a 10 microliter reaction mixture and incubated for 16 hours at 16 ° C.

The ligation products are transformed into XL-1 Blue or DH5-α E. coli cells by electroporation as described above. After recovery in SOC, cells are plated on LB plates containing 100 micrograms / ml ampicillin and grown overnight at 37 ° C. These plates are then replicated into plates containing 25 micrograms / ml kanamycin and grown overnight. The resulting colonies contain both the ampicillin resistance gene that is present in the pT7Blue vector and the newly introduced gene

127 kanamycin resistance. Colonies were picked into LB containing 25 micrograms / ml kanamycin and plasmid DNA was isolated from cultured cells using the Qiagen miniprep protocol (Qiagen, Gaithersburg, MD, USA).

Several PCR amplification assays are performed on these plasmids to verify that kanamycin is incorporated into H. pylori / ORF genes and to determine the orientation of kanamycin resistance gene insertion relative to H. pylori / ORF genes. To verify that the kanamycin cassette was incorporated into the H. pylori sequence, plasmid DNAs are used as templates for PCR amplification with a set of primers that were originally used to clone H. pylori genes / ORFs. The correct PCR product has the size of the deleted gene / ORF, but increased by the size of the added 1.4 kilobase kanamycin cassette. To avoid the potential polar effects of the kanamycin resistance cassette on H. pylori gene expression, the orientation of the kanamycin resistance gene relative to the knock-out gene / ORF is determined and both orientations are finally used in H. pylori transformations (see below). To determine the orientation of the kanamycin resistance gene insertions, primers from the ends of the kanamycin resistance gene ("Kan-1" 5'ATCTTACCTATCACCTCAAAT-3 '(SEQ. No. 255)) and "Kan-2 5'AGACAGCAACATCTTTGTGAA-3' (SEQ. No. 256)). The orientation of the kanamycin cassette relative to the H. pylori sequence is determined using each of the cloning primers in conjunction with each of the Kan primers (4 primer combinations). Positive clones are termed either Λ "oriented (same transcription direction of both H. pylori and kanamycin resistance gene) or" B "oriented (transcription direction of H. pylori gene is opposite to the transcription direction of kanamycin gene). Clones with the same orientation (A or B) were pooled for subsequent experiments and independently transformed into H. pylori.

Transformation of plasmid DNA into H. pylori cells

Two H. pylori strains are used for transformation: ATCC 55679, a clinical isolate that provided DNA to obtain a H. pylori sequence database, and AH244, an isolate that has been passaged and has the ability to colonize mouse stomach. Cells for transformation were grown at 37 ° C, 10% CO 2, 100% humidity, either on sheep blood agar plates or in Bruceil liquid medium. Cells grow into

128 are examined by a microscope to determine whether they are "healthy" (moving actively) and whether they are contaminated. If cells are grown on plates, they are harvested by scraping from the plate with a sterile loop, suspended in 1 ml Brucella medium, settled (1 minute, highest speed in an Eppendorf microcentrifuge), and suspended in 200 microliters of Brucella medium. If grown in liquid Brucella medium, they are centrifuged (15 minutes at 3000 rpm in a Beckman TJ6 centrifuge) and the cell pellet is suspended in 200 microliters of Brucella medium. An aliquot of the cells is taken to determine the optical density at 600 nm to calculate the cell concentration. An aliquot (1-5 OD ₆₀₀ units / 25 microlitres) of suspended cells is placed on preheated sheep blood agar plates and the plates are further incubated at 37 ° C, 6% CO ₂ , 100% humidity for 4 hours. After this incubation, 10 microliters of plasmid DNA (100 micrograms per microliter) was applied to these cells. In parallel, a positive control (plasmid DNA with a ronuclease H gene interrupted by the kanamycin resistance gene) and a negative control (without plasmid DNA) were made. These plates are returned to 37 ° C, 6% CO ₂ for an additional 4 hours for incubation. The cells are then plated on plates using a sponge soaked in Brucella medium and grown for 20 hours at 37 ° C, 6% CO ₂ . The cells are then transferred to sheep blood agar plates containing 25 micrograms / ml kanamycin and grown for 3-5 days at 37 ° C, 6% CO ₂ , 100% humidity. If colonies appear, they are harvested and regrowed as patches on fresh sheep blood agar plates containing 25 micrograms / ml kanamycin.

Three sets of PCR assays were performed to verify that colonies of transformants were formed by homologous recombination of the correct chromosomal sites. The template for PCR (colony DNA) is obtained by the rapid DNA boiling method as follows. An aliquot of the colony (toothed colony) is placed in 100 microliters of 1% Triton X-100, 20 mM Tris, pH 8.5, and boiled for 6 minutes. An equal volume of a 1: 1 mixture of phenol and chloroform was added and vortexed. The mixture is centrifuged on a microcentrifuge for 5 minutes and the supernatant is used as a DNA template for PCR together with the following primers to verify homologous recombination at the correct chromosome site.

TEST 1. PCR with cloning primers originally used for gene / ORF amplification. Positive result of homologous recombination at the right site at

The 129 chromosome should be seen as a single PCR product, the size of which is equal to the deleted gene / ORF, but which is increased by the size of the added 1.4 kilobase kanamycin cassette. A PCR product having an exact gene / ORF size demonstrates that the gene has not been knocked out and that the transformant is not the result of homologous recombination at the correct location on the chromosome.

TEST 2. PCR with F3 (primer designed for sequences upstream of the gene / ORF and not present in the plasmid), and either Kan-1 or Kan-2 primer (primers designed from the ends of the kanamycin resistance gene), whether plasmid DNA of "A" or "B orientation" is used. Homologous recombination at the correct site on the chromosome will result in a single PCR product of the expected size (i.e., from the F3 site to the insertion site of the kanamycin resistance gene). No PCR product or PCR product (s) of the wrong size will indicate that the plasmid has not integrated at the correct site and that the gene has not been knocked out.

TEST 3. PCR with R3 (primer designed downstream of the gene / ORF and not present in the plasmid) and with either Kan-1 or Kan-2 primer, depending on whether plasmid DNA s, A 'is used. or "B orientation." Homologous recombination at the correct site on the chromosome will result in a single PCR product of the expected size (i.e., from the site of insertion of the kanamycin resistance gene to the downstream position of R3). Again, no PCR product or incorrectly sized PCR product (s) will indicate that the plasmid has not integrated at the correct site and that the gene has not been knocked out.

Transformants showing positive results in all three assays indicated that the gene was not necessary for in vitro survival.

A negative result in any of the above three assays for each transformant indicated that the gene had not been disrupted and that the gene was necessary for in vitro survival.

If no colonies are formed from the two independent transformations, while the positive control with the interrupted ribonuclease H plasmid DNA generates transformants, the plasmid DNA is further analyzed by PCR

130 on DNA from the transformed population prior to plating to form colonies. This verifies that the plasmid can enter the cell and undergo homologous recombination at the right site. Briefly, plasmid DNA is incubated in accordance with the transformation protocol described above. DNA is extracted from H. pylori cells immediately after incubation with plasmid DNA and the DNA is used as a template for Test 2 and Test 3 above. Positive results in Test 2 and Test 3 would verify that plasmid DNA could enter the cell and subject with homologous recombination at the right site of the chromosome. If test 2 and test 3 are positive, the inability to obtain viable transformants indicates that the gene is essential and the cell in which the gene is disrupted is unable to form a colony.

VII. Highly effective drug search test

Protein cloning, expression and purification

Kioning, transformation, expression and purification of the H. pylori target gene and its protein product, e.g. of the H. pylori enzyme to be used in the high throughput drug screen is performed essentially as described in Examples II and III above. As a specific example, the development and use of a screening assay for a particular H. pylori-peptidylpropyl cis-trans isomerase gene product is described below.

Enzymatic test

The assay is essentially described by Fisher (Fischer, G., et. Al. (1984) Biomed. Biochim. Acta 43: 1101-1111). The assay measures cis-trans isomerization of Ala-Pro binding in the N-succinyl-Ala-Ala-Pro-Phe-p-nitroanilide test peptide (Sigma # S-7388, Lot # 84H5805). The assay is coupled to α-chymotrypsin, whereby the protease is capable of cleaving the test peptide only when the Ala-Pro binding is trans. The conversion of the test peptide to the trans isomer is monitored at 390 nm on a Beckman Model DU-650 spectrophotometer. Data is collected every second with an average scan time of 0.5 seconds. Assays are performed in 35 mM Hepes, pH 8.0, in a final volume of 400 μΙ, with 10 μΜ α-chymotrypsin (bovine pancreas type 15, Sigma # C-7762, lot 23H7020) and 10 nM PPIase.

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To initiate the reaction, 10 μΙ of substrate (2 mM N-succinyl-Ala-Ala-Pro-Phep-nitroanilide in DMSO) is added to 390 μΙ of the reaction mixture at room temperature.

Enzymatic assay in crude bacterial extract ml culture of Helicobacter pylori (strain J99) in Brucella medium is taken in the middle logarithmic phase (OD 90 nm ~ 1) and suspended in the lysis buffer with the following protease inhibitors: 1 mM PMSF, and 10 pg / ml each aprotinin, leupeptin, pepstatin, TLCK, TPCK, and soybean trypsin inhibitor. The suspension is frozen and thawed in 3 cycles (15 minutes at -70 ° C, then 30 minutes at room temperature), followed by sonication (three times for 20 seconds). The lysate is centrifuged (12,000 g x 30 minutes) and the supernatant is analyzed for enzymatic activity as described above.

Many H. pylori enzymes can be expressed in E. coli at high levels and in active form. Such high yields of purified proteins are used in various highly efficient drug screening assays.

Vili. Truncated gene expression and protein production

Identification, cloning and expression of recombinant Helicobacter pylori sequences

To facilitate the cloning, expression and purification of the membrane proteins from H. pylori, the pET gene expression system (Novagen) was selected for cloning and expression of recombinant proteins in Escherichia coli. Further, for proteins having a signal sequence at their amino terminus, a DNA sequence encoding a His-tag was fused to the 5 'end of the interesting H. pylori DNA sequences to facilitate purification of recombinant protein products. In some cases, the DNA sequence was cloned in frame with a glutathione-S-transferase protein to form a GST-fusion protein. The vectors used in this case were the pGEX series from Pharmacia LKB (Uppsala, Sweden).

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PCR amplification and cloning of ORF-containing DNA sequences for membrane and secreted proteins from Helicobacter pylori J99 strain.

Sequences selected (from the DNA sequence listing of the invention) for cloning from H. pylori J99 strain were prepared for amplification cloning by polymerase chain reaction (PCR). Synthetic oligonucleotide primers for each subject ORF (Table 11) specific for the predicted mature 5 'end of the ORF and downstream (3 *) from the predicted translation termination codon or at specific points within the coding region were designed and purchased (GibcoBRL Life Technologies, Gaithersburg, MD, USA). All forward primers (specific for the 5 'end of the subject ORF region) were designed to include either a SamHI or Nde I restriction site. These primers within the Nde \ restriction site sequence were designed to allow protein translation to be initiated at the methionine residue (encoded within the NDe \ restriction site sequence for the production of a non-His-tagged recombinant protein) or fused to a DNA sequence encoding His-tag (for the production of His tag recombinant protein), followed by a coding sequence for the remainder of the native H. pylori DNA. The HI restriction site primer was produced to fuse the H. pylori-specific sequence within the framework of the glutathione-S-transferase gene terminus in pGEX vectors (Pharmacia LKB, Uppsala, Sweden). All reverse oligonucleotide primers were designed to include an EcoRI restriction site at the 5 'end. Several reverse oligonucleotide primers were selected that would cause truncation of the polypeptide to remove some portions of the C-terminus, and in these cases an EcoRI restriction site at the 5 'end was followed by a translation termination codon. This combination of primers would allow the subject ORF (or a portion of the subject ORF) to be cloned into pET28b (to form a His-tagged recombinant protein), pET30a (to form a non-His tagged or native recombinant protein) or pGEX-4T or pGEX- 5X (to form a GST fusion protein). The vector pET28b provides the encoding of an additional 20 amino-terminal amino acids (plus methionine at the Nde I restriction site), including a stretch of six histidine residues that form His tag, while pGEX vectors fuse the H. pylori protein to 26,000 Da glutathione-S-transferase protein.

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Genomic DNA prepared from a H. pylori J99 strain (ATCC 55679) was used as a template DNA source for PCR amplification reactions (Current Protocols in Molecular Biology, John Wiley &amp; Sons, Inc., F. Ausubel et al., Eds., 1994) . To amplify the DNA sequence containing the H. pylori specific ORF, genomic DNA (50 nanograms) was introduced into a reaction tube containing 200 nanograms of both the direct and reverse synthetic oligonucleotide primer specific for the ORF in question and 45 microliters purchased by SuperMix PCR (GibcoBRL Life Technologies, Gaithersburg, MD) ) in a total volume of 50 microliters. SuperMix PCR is supplied in concentrations of 1.1 X and contains 22 mM Tris-HCl (pH 8.4), 55 mM KCl, 1.65 mM MgCl 2, 220 micromoles of each of the following: dATP, dCTP, dGTP and dTTP, 22 units recombinant Taq polymerase (s) and stabilizers. The following thermal cycling conditions were used to obtain amplified DNA products for each ORF using a Perkin Elmer Cetus / Gene Amp PCR System thermal cycler.

Table 11: Oligonucleotide primers

Gene and location sequence Vac38-BamHI post signal sequence CGGGATCCGAAGGTGATGGTGTTTAT ATAGG (SEQ ID NO: 271) Vac38- Ndel post signal sequence CGCATATGGAAGGTGATGGTGTTTAT ATAGGG (SEQ ID NO: 272) Vac38-EcoRI / stop codon (removes C-terminal third of protein) GCGAATTCTCACTCTTTCCAATAGTTT GCTGCAGAGC (SEQ ID NO: 273) Vac38-EcoRI / stop codon (removes C-terminal 11 amino acids) CCGGAATTCTTAATCCCGTTTCAAAT GGTAATAAAGG (SEQ ID NO: 274) Vac38-EcoRI down from the native stop codon GCGAATTCCCTTTTATTTAAAAAGTGT AGTTATACC (SEQ ID NO: 275)

Sequences for Vac38 (full-length or shortened)

Denaturation at 94 ° C for 30 sec cycles at 94 ° C for 15 sec, 55 ° C for 15 sec and 72 ° C for 1.5 min Reactions were terminated at 72 ° C for 8 min

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After the thermal cycling reactions were completed, each amplified DNA sample was electrophoresed on 1.0% agarose gels. DNA was visualized by exposure to ethidium bromide and long wave UV radiation and excised in gel sections. DNA was purified by Wizard PCR Preps Krt (Promega Corp., Madison, WI, USA) and then subjected to digestion with SamHI and EcoRI (Current Protocols in Molecular Biology, John Wiley &amp; Sons, Inc., F. Ausubel et al.). , eds., 1994). The digested PCR amplicon was then re-subjected to electrophoresis and purification as before.

Ligation of H. pylori DNA sequences into cloning vectors

The vector pOK12 (J. Vieira and J. Messing, Gene 100: 189-194, 1991) was prepared for cloning by digestion with SamHI and EcoRI or Ndei and EcoRI for Vac41 (Current Protocols in Molecular Biology, John Wiley and Sons, Inc.). (F. Ausubel et al., Eds., 1994). Vectors were subjected to electrophoresis on 1.0% agarose gels and purified using Wizard Wizard Preps kit (Promega Corp., Madison, WI, USA). After ligation of the purified cleavage vector and the purified cleaved amplified H. pylori ORF, the ligation reaction products were transformed into competent E. coli JM109 cells according to standard methods (Current Protocols in Molecular Biology, John Wiley &amp; Sons, Inc., F. Ausubel et al., eds., 1994). Individual bacterial colonies were screened for those containing the correct recombinant plasmids by incubation in LB culture solution overnight (plus 25 µg / ml kanamycin sulfate), followed by plasmid DNA preparation using the Magic Minipreps system (Promega Corp., Madison, WI, USA) and then analyzed by restriction digestion (Current Protocols in Molecular Biology, John Wiley &amp; Sons, Inc., F. Ausubel et al., Eds., 1994).

Cloning of H. pylori DNA sequences into prokaryotic expression vectors pET28b and pGEX4Ta

PET28b and pET30a expression vectors were prepared for cloning by digestion with Ndei and EcoRI, and the vector pGEX4T-3 was prepared for cloning by digestion with SamHI and EcoRI (Current Protocols in Molecular Biology, John Wiley &amp; Sons, Inc., F. Ausubel et al., eds., 1994). H. pylori DNA sequences were removed from the

135 plasmid chains of pOK12 by digestion with NdeI and EcoRI or SamHI and EcoRI (Current Protocols in Molecular Biology, John Wiley &amp; Sons, Inc., F. Ausubel et al., Eds., 1994). The DNA sequences of pET28b, pET30a, pGEX4T-3, and H. pylori were subjected to electrophoresis on a 1% agarose gel and purified using the Wizard PCR Preps kit (Promega Corp., Madison WI, USA). After ligation of the purified cleaved expression vector and the purified cleaved H. pylori DNA sequences, the ligation reaction products were transformed into competent E. coli JM109 cells (Current Protocols in Molecular Biology, John Wiley &amp; Sons, Inc., F. Ausubel et al., Eds. , 1994). Individual bacterial colonies were screened for those containing the correct recombinant plasmids by preparing plasmid DNA as described above, followed by restriction digestion analysis and DNA sequencing (Current Protocols in Molecular Biology, John Wiley &amp; Sons, Inc., F. Ausubel et al. , eds., 1994). These recombinant plasmids were then used to transform specific E. coli expression strains.

Transformation of competent bacteria with recombinant expression plasmids

Competent bacterial strains (BL21 (DE3), BL21 (DE3) pLyS, HMS174 (DE3) and HMS174 (DE3) pLysS) were prepared and transformed with recombinant expression plasmids carrying cloned H. pylori sequences according to standard methods (Current Protocols in Molecular Biology, John) Wiley and Sons, Inc., F. Ausubel et al., Eds., 1994) These expression host strains contain a chromosomal copy of the T7 RNA polymerase gene, these hosts being the bacteriophage DE3 lysogens, a lambda derivative carrying the lacI gene, the lacUV5 promoter. and the T7 RNA polymerase gene The expression of the T7 RNA polymerase is induced by the addition of isopropyl-β-D-thiogalactoside (IPTG) and the T7 RNA polymerase then transcribes any target plasmid, for example pET28b, which carries the T7 promoter sequence and the gene of interest.

Competent bacterial strains JM109 and DH5α were prepared and transformed with recombinant expression plasmids pGEX4T-3 carrying cloned H. pylori sequences according to standard methods (Current Protocols in Molecular Biology, John Wiley &amp; Sons, Inc., F. Ausubel et al., Eds. , 1994).

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Expression of recombinant H. pylori sequences in E. coli

Transfiorants were harvested from LB agar plates containing 25 µg / ml kanamycin sulfate (provides maintenance of recombinant plasmids based on pET28b) or 100 µg / ml ampicillin (provided maintenance of recombinant plasmids pGEX4T-3) and used to inoculate a 25 µg / ml culture solution containing 25 µg / ml of kanamycin. sulfate or 100 µg / ml ampicillin and cultured to an optical density of 0.5 to 1.0 OD units at 600 nm, when 1 mM IPTG was added to the culture for one to three hours to induce gene expression of recombinant H DNA constructs. pylori. After inducing gene expression by IPTG, the bacteria were pelleted by centrifugation and resuspended in SDS-PAGE solubilization buffer and subjected to SDS-PAGE (Current Protocols in Molecular Biology, John Wiley &amp; Sons, Inc., F. Ausubel et al., Eds. , 1994 / Proteins were visualized by Coomassie Brilliant Blue induction or detected by Western Immunoblotting using specific antiHis tagged monoclonal antibody (Clontech, Palo Alto, CA, USA) or antiGST tagged antibody (Pharmacia LKB) using standard methods (Current Protocols in Molecular Biology (John Wiley &amp; Sons, Inc., F. Ausubel et al., Eds., 1994) The host strain that provided the highest level of recombinant protein production was then selected for use in large-scale induction to purify the recombinant protein. strains were HMS174 (DE3) (pET28b-based constructs) and DH5a (pGEX4T3-based constructs).

Removal of the C-terminal regions in both systems appears to improve expression levels, although this increase was much more pronounced in the GST-fusion system. All recombinant proteins produced had a predicted molecular weight based on the DNA sequence plus, if desired, the size of the fusion tag. The truncated portion of the H. pylori protein contains some extremely hydrophobic regions and their removal may be a reason for increased expression.

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equivalents

Many equivalents of the specific embodiments and methods described herein will be apparent to, or able to be determined by, routine experimentation to those skilled in the art. These equivalents fall within the scope of the following claims.

138

LIST OF SEQUENCES

1) GENERAL INFORMATION:

(i) APPLICANT:

(A) NAME: Astra Aktiebolag (B) STREET: S-151 85 (C) CITY: Sodertalje (D) COUNTRY:

(E) COUNTRY: Sweden (F) POSTAL CODE (ZIP) (ii) NAME OF THE INVENTION: Nucleic acid and amino acid sequences related to Helicobacter pylori and vaccine compositions containing them (iii) NUMBER OF SEQUENCES: 275 (iv) COMPUTER READABLE FORM:

(A) MEDIA TYPE: CD / ROM ISO9660 (B) COMPUTER (C) OPERATING SYSTEM:

(D) SOFTWARE:

(v) INFORMATION ON APPLICATION FORM:

(A) APPLICATION NUMBER (B) DATE OF SUBMISSION:

(vi) PREVIOUS APPLICATION DETAILS:

(A) APPLICATION NUMBER: US 08 / 759,625 (B) filing date: 05-DEC-1996 (vii) PREVIOUS APPLICATION DETAILS:

(A) APPLICATION NUMBER: US 08 / 823,745 (B) SUBMISSION DATE: 25-MAR-1997 (viii) PREVIOUS APPLICATION DETAILS:

(A) APPLICATION NUMBER: US 08 / 891,928 (B) filing date: 14-JULY-1997 (ix) CORRUPTION ADDRESS:

(A) ADDRESS: LAHIVE & COCKFIELD (B) STREET: 28 State Street

139 (C) CITY: Boston (D) COUNTRY: Massachusetts (E) COUNTRY: USA (F) ZIP Code: 02109-1875 (x) REFERENCE INFORMATION:

(A) NAME: Mandragouras, Amy E.

(B) REGISTRATION NUMBER: 36.207 (C) BRAND: GTN-011CP2PC (xi) TELECOMMUNICATION INFORMATION:

(A) Phone: (617)227-7400 (B) TELEFAX: (617)227-5941 (2) 1:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 687 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular (ii) MOLECULA TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE : NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) NAME / KEY: different characters (B) LOCATION 1 ... 687 (xi) SEQUENCE DESCRIPTION: SEQUENCE NO. 1:

ATGAGATTTA AGGGTTCAAG AGTGGAAGCG TTTTTAGGAG CGTTAGAATT TCAAGAGAAT GAATATGAAG AGTTTAAAGA GCTTTATGAG AGCTTAAAAA CCAAGCAAAA GCCCCACACT TTGTTCATTT CTTGCGTGGA TTCACGAGTC GTGCCTAATT TAATCACAGG CACCCAACCG GGCGAATTGT ATGTGATCCG CAACATGGGC AATGTGATCC CCCCTAAAAC AAGCTATAAA GAATCCCTTT CTACCATTGC GAGCGTTGAA TACGCTATCG CGCATGTGGG CGTTCAAAAC TTAATCATTT GCGGGCATAG CGATTGTGGG GCTTGCGGGA GCATTCATTT AATCCATGAT GAAACCACCA AAGCTAAAAC CCCTTACATT GCAAACTGGA TACAATTTTT AGAGCCTATT

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180

240

300

360

420

140

AAAGAAGAAT TAAAAAACCA CCCGCAATTC AGCAACCATT TCGCCAAGCG TTCATGGCTT 480 ACAGAGCGTT TGAATGCGCG CTTGCAACTC AACAACCTCT TAAGCTATGA TTTCATTCAA 540 GAAAGAGTAA TAAATAACGA ATTAAAAATT TTTGGTTGGC ACTATATCAT AGAAACAGGC 600 AGGATTTATA ATTATAATTT TGAAAGCCAT TTTTTTGAGC CGATTGAAGA AACCATTAAA 660 CAAAGGATAA GTCATGAAAA CTTCTAA 687 (2) INFORMATION FOR SEQ ID NO. 2:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 666 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular (ii) MOLECULA TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE : NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) NAME / KEY: various characters (B) LOCATION 1 ... 666 (xi) SEQUENCE DESCRIPTION: SEQUENCE NO. 2:

GTGGAAGCGT TTTTAGGAGC GTTAGAATTT CAAGAGAATG AATATGAAGA GTTTAAAGAG 60 CTTTATGAGA GCTTAAAAAC CAAGCAAAAG CCCCACACTT TGTTCATTTC TTGCGTGGAT 120 TCACGAGTCG TGCCTAATTT AATCACAGGC ACCCAACCGG GCGAATTGTA TGTGATCCGC 180 AACATGGGCA ATGTGATCCC CCCTAAAACA AGCTATAAAG AATCCCTTTC TACCATTGCG 240 AGCGTTGAAT ACGCTATCGC GCATGTGGGC GTTCAAAACT TAATCATTTG CGGGCATAGC 300 GATTGTGGGG CTTGCGGGAG CATTCATTTA ATCCATGATG AAACCACCAA AGCTAAAACC 360 CCTTACATTG CAAACTGGAT ACAATTTTTA GAGCCTATTA AAGAAGAATT AAAAAACCAC 420 CCGCAATTCA GCAACCATTT CGCCAAGCGT TCATGGCTTA CAGAGCGTTT GAATGCGCGC 480 TTGCAACTCA ACAACCTCTT AAGCTATGAT TTCATTCAAG AAAGAGTAAT AAATAACGAA 540 TTAAAAATTT TTGGTTGGCA CTATATCATA GAAACAGGCA GGATTTATAA TTATAATTTT 600 GAAAGCCATT TTTTTGAGCC GATTGAAGAA ACCATTAAAC ÄAAGGATÄAG TCATGAAAAC TTCTAA 660 666 (2) INFORMATION FOR SEQ ID NO. 3:

141 (i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 1008 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLDGIA: circular (ii) MOLECULAR TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE : NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix) SIGN:

(A) NAME / KEY: various characters (B) LOCATION 1 ... 1008 (xi) SEQUENCE DESCRIPTION: SEQUENCE NO. 3:

ATGTTAGTTA CTCGTTTTAA AAAAGCCTTC ATTTCTTATT CTTTAGGCGT GCTTGTTGTT 60

TCATTATTAT TGAATGTGTG CAACGCTTCA GCACAAGAAG TCAAAGTCAA GGATTATTTT 120

GGGGAGCAAA CCATAAAGCT TCCTGTTTCC AAAATAGCCT ATATAGGGAG TTATGTAGAA 180

GTGCCTGCCA TGCTTAATGT TTGGGATAGG GTTGTAGGCG TTTCTGATTA TGCCTTTAAG 240

GATGACATTG TCAAAGCCAC TCTCAAAGGC 300 GAGGATCTTA ÄACGAGTCAA ACACATGAGC 300

ACCGATCATA CAGCCGCGTT GAATGTGGAA TTATTAAAAA AGCTTAGCCC TGATCTTGTG 360

GTAACCTTTG TGGGTAACCC TAAAGCGGTA GAGCATGCGA AAAAATTTGG GATTTCATTC 420

CTTTCTTTCC AAGAGACAAC GATTGCAGAG GCCATGCAAG CTATGCAAGC TCAAGCCACG 480

GTCTTAGAAA TTGACGCTTC CAAAAAATTC GCCAAAATGC AAGAAACTTT GGACTTTATT 540

GCTGAGCGTT TGAAGGGCGT TAAAAAGAAA AAGGGGGTGG AGCTTTTCCA TAAAGCCAAT 600

AAAATCAGCG GCCATCAAGC CATTAGCTCA GACATTTTAG AAAAAGGGGG TATAGATAAT 660

TTTGGCTTGA AATACGTTAA GTTTGGACGC GCTGACATTA GTGTGGAAAA AATCGTTAAA 720

GAAAACCCTG AAATCATTTT CATTTGGTGG GTAAGCCCAC TCACTCCTGA AGACGTGTTG 780

AACAACCCTA AATTTTCCAC TATCAAAGCC ATTAAAAATA AGCAAGTCTA TAAGCTCCCC 840

ACGATGGATA TTGGCGGTCC TAGAGCCCCA CTCATTAGTC TTTTTATCGC TTTAAAAGCC 900

CACCCTGAAG CCTTTAAAGG CGTGGATATT AATGCGATAG TCAAAGATTA TTATAAAGTG 960

GTCTTTGATT TGAATGATGC GGAAATTGAG CCATTCTTAT GGCACTGA 1008 (2) INFORMATION FOR SEQUENCE NO. 4:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 825 base pairs (B) TYPE: nucleic acid

142 (C) FIBER NUMBER: two (D) TOPOLOGY: circular (ii) MOLECULA TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) NAME / KEY: various characters (B) LOCATION 1 ... 825 (xi) SEQUENCE DESCRIPTION: sequence no. 4:

ATGTTAGTTA CTCGTTTTAA AAAAGCCTTC ATTTCTTATT CTTTAGGCGT GCTTGTTGTT TCATTATTAT TGAATGTGTG CAACGCTTCA GCACAAGAAG TCAAAGTCAA GGATTATTTT GGGGAGCAAA CCATAAAGCT TCCTGTTTCC AAAATAGCCT ATATAGGGAG TTATGTAGAA GTGCCTGCCA TGCTTAATGT TTGGGATAGG GTTGTAGGCG TTTCTGATTA TGCCTTTAAG GATGACATTG TCAAAGCCAC TCTCAAAGGC GAGGATCTTA AACGAGTCAA ACACATGAGC ACCGATCATA CAGCCGCGTT GAATGTGGAA TTATTAAAAA AGCTTAGCCC TGATCTTGTG GTAACCTTTG TGGGTAACCC TAÄAGCGGTA GAGCATGCGÄ AAÄAATTTGG GATTTCATTC CTTTCTTTCC AAGAGACAAC GATTGCAGAG GCCATGCAAG CTATGCAAGC TCAAGCCACG GTCTTAGAAA TTGACGCTTC CAAAAAATTC GCCAAAATGC AAGAAACTTT GGACTTTATT GCTGATCGTT TGAAGGGCGT TAAAAAGAAA AAGGGGGTGG AGCTTTTCCA TAAAGCCAAT AAAATCAGCG GCCATCAAGC CATTAACTCA GACATTTTAC AACAAGGGGG TATTGATAAT TTTGGCTTGA AATACGTCAA GTTTGGACGC GCTGACATTA GTGTGGAAAA AATCGTTAAA GAAAACCCTG AAATCATTTT CATTAGGTGG GTAACCCCAC TCACTCCTGA TTACGTGTTG AACÄACCCAA AATTTTCTAC TATCAATGCC ATTAAAAACA tatami (2) INFORMATION FOR SEQ ID NO. 5:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 1287 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular (ii) MOLECULA TYPE: DNA (genomic)

120

180

240

300

360

420

480

540

600

660

720

780

825 (iii) HYPOTHETICAL: NO

143

(iv) ANTI-SENSE: NO (Vi) ORIGINAL SOURCE: (A) ORGANISM: Helicobacter pylori (Ix) SIGN: (A) TITLE / KEY: (B) LOCATION different characters 1 ... 1287 (Xi) SEQUENCE DESCRIPTION: SEQ ID NO. 5:

ATGAAGAAAA AATTTCTGTC ATTAACCTTA GGTTCGCTTT TAGTTTCCGC TTTAAGCGCT 60 GAAGACAACG GCTTTTTTGT GAGCGCCGGC TATCAAATCG GTGAATCCGC TCAAATGGTG 120 AAAAACACCA AAGGCATTCA AGATCTTTCA GACAGCTATG AAAGATTGAA CAACCTTTTA 180 ACGAATTATA GCGTCCTAAA CGCTCTCATC AGGCAGTCCG CCGACCCCAA CGCCATCAAT 240 AACGCAAGGG GCAATTTGAA CGCGAGCGCG AAGAATTTGA TCAATGATAA AAAGAATTCC 300 CCGGCGTATC AAGCCGTGCT TTTAGCCTTG AATGCGGCAG CGGGGTTGTG GCAAGTCATG 360 AGCTATGCGA TCAGCCCTTG TGGTCCCGGT AAAGACACAA GCAAAAATGG GGGCGTTCAA 420 ACTTTCCACA ACACGCCTTC AAATCAATGG GGAGGCACTA CCATTACTTG TGGCACTACT 480 GGTTATGAAC CAGGACCATA CAGCATTTTA TCCACTGAAA ATTACGCGAA AATCAATAAA 540 GCTTATCAAA TCATCCAAAA GGCTTTTGGG AGCAGCGGAA AAGATATTCC TGCCTTAAGC 600 GACACCAACA CAGAACTCAA ATTCACAATC AATAAAAATA ATGGAAACAC GAATACGAAT 660 AATAATGGAG AAGAAATTGT TACAAAAAAT AACGCTCAAG TTCTTTTAGA ACAGGCTAGC 720 ACCATTATAA CTACCCTTAA TAGCGCATGC CCATGGATCA ACAATGGTGG TGCAGGTGGT 780 GCGAGTAGTG GTAGTTTATG GGAAGGAATA TATTTGAAAG GCGATGGGAG CGCTTGCGGG 840 ATTTTTAAAA ATGAAATCAG CGCGATTCAA GACATGATCA AAAACGCTGC AATAGCCGTA 900 GAGCAATCCA AGATCGTTGC TGCAAACGCG CAAAACCAGC GCAACCTAGA CACCGGGAAG 960 ACATTCAACC CCTATAAAGA CGCCAACTTC GCCCAAAGCA TGTTCGCTAA CGCCAAAGCG 1020 CAAGCGGAGA TTTTAAACCG CGCCCAAGCA GTGGTGAAAG ACTTTGAAAG AATCCCTGCA 1080 GAGTTCGTAA AAGACTCTTT AGGGGTGTGC CATGAAGTGC AAAACGGCCA TCTCCGTGGC 1140 ACGCCATCCG GCACGGTAAC TGATAACACT TGGGGAGCCG GTTGCGCGTA TGTGGGAGAG 1200 ACCGTAACGA ATCTAAAAGA CAGCATCGCT CATTTTGGCG ACCAAGCCGA GCGAATCCAT 1260 AACGCGCGCA ACCTCGCTAC ACTTTAG 1287

(2) INFORMATION FOR SEQUENCE NO. 6:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 537 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular (ii) MOLECULA TYPE: DNA (genomic)

144 (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) NAME / KEY: different characters (B) LOCATION 1 ... 537 (xi) SEQUENCE DESCRIPTION: SEQUENCE NO. 6:

ATGAACCCCT TATTGCAAGA TTATGCGCGC ATCCTTTTAG AATGGAATCA AACGCACAAC TTGAGCGGCG CGAGAAATTT AAGCGAATTA GAACCCCAGA TCACAGACGC TCTAAAGCCC TTAGAATTTG TCAAAGATTT TAAAAGCTGC TTGGATATTG GGAGCGGGGC GGGACTTCCT GCTATCCCTT TAGCCCTTGA AAAACCTGAA GCGCAATTCA TTCTTTTAGA GCCAAGGGTA AAAAGAGCGG CTTTTTTAAA CTACCTTAAA AGCGTTTTGC CTTTAAACAA CATTGAAATC ATTAAAAAGC GTTTAGAAGA TTATCAAAAT CTTTTACAAG TGGATTTAAT CACTTCTAGA GCGGTCGCTA GCTCTTCTTT TTTGATAGAA AAAAGCCAAC GCTTCCTAAA AGATAAGGGG TATTTTTTAT TCTATAAAGG CGAGCAGTTA AAGAATGAAA TCGCTTATAA AACCACTGAA TGCTTTATGC ATCAAAAGCG CGTTTATTTT TACAAATCAA AGGAAAGTTT ATGTTAA (2) INFORMATION FOR SEQUENCE NO. 7:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 723 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular (ii) MOLECULAR TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE : NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori

120

180

240

300

360

420

480

537 (ix) SIGN:

(A) TITLE / KEY: various characters (B) LOCATION 1 ... 723

145 (xi) SEQUENCE DESCRIPTION: SEQ ID NO. 7:

TTGGGTCTTA AAAAACGAGC TATTTTATGG TCTTTAATGG GATTTTGTGC AGGATTGAGC 60 GCGCTTGATT ATGACACCCT AGACCCAAAA TATTACAAAT ATATCAAGTA TTATAAGGCT 120 TATGAAGATA AAGAAGTTGA AGAATTGATC AGAGACTTGA AAAGGGCGAA CGCTAAAAGC 180 GGGCTTATTT TAGGGATCAA TACCGGTTTT TTTTATAACC ATGAAATCAT GGTCAAAACC 240 AATAGCTCCA GTATCACCGG GAATATTTTA AATTATTTGT TCGCCTATGG CTTGCGTTTT 300 GGCTATCAAA CTTTCAGGCC GTCGTTTTTT GCGCGCTTGG TTAAGCCCAA TATCATTGGC 360 AGGCGCATCT ATATTCAATA TTATGGAGGA GCTCCTAAGA AAGCGGGCTT TGGGAGCGTG 420 GGGTTTCAAT CGGTCATGTT GAATGGGGAT TTTTTATTAG ACTTTCCTTT GCCCTTTGTG 480 GGGAAATACC TTTATATGGG GGGGTATATG GGTTTAGGCT TGGGGGTTGT GGCGCATGGG 540 GTGAATTATA CGGCGGAATG GGGGATGTCT TTTAACGCAG GATTGGCTCT AACGGTATTA 600 GAAAAAAACC GCATTGAATT TGAATTTAAA ATTTTGAATA ATTTCCCTTT TTTGCAATCT 660 AATTCTTCAA AAGAGACTTG GTGGGGAGCT ATAGCAAGCA TTGGGTATCA ATATGTGTTC 720 TAA 723

(2) INFORMATION FOR SEQUENCE NO. 8:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 942 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular (ii) MOLECULA TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE : NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) NAME / KEY: various characters (B) LOCATION 1 ... 942 (xi) SEQUENCE DESCRIPTION: SEQUENCE NO. 8:

TTGAAACTCA AATACTGGTT AGTTTATCTG GCGTTCATTA TAGGACTTCA AGCGACAGAT 60

TATGACAATT TAGAAGAAGA AAACCAACAA TTAGACGAAA AAATAAACAA TTTAAAGCGA 120

CAGCTCACCG AAAAAGGGT TTCACCCAAA GAGATGGATA AGGATAAGTT TGAAGAAGAA 180

TATTTAGAGC GAACTTACCC AAAGATTTCT TCAAAGAAAA GAAAAAAATT GCTCAAATCT 240

146

TTTTCCATAG CCGATGATAA GAGTGGGGTG TTTTTAGGGG GCGGGTATGC TTATGGGGAA CTTAACTTGT CTTATCAAGG GGAGATGTTA GACAGGTATG GCGCAAATGC CCCTAGCGCG TTTAAAAACA ATATCAATAT TAACGCTCCT GTTTCTATGA TTAGCGTTAA ATTTGGGTAT CAAAAATACT TCGTGCCTTA TTTTGGGACA CGATTTTATG GGGATTTGTT GCTTGGGGGA GGGGCGTTAA AAGAGAACGC GCTCAAGCAG CCTGTAGGCT CGTTTTTTTA TGTTTTAGGG GCTATGAATA CCGATTTATT GTTTGACATG CCTTTAGATT TTAAGACTAA AAAGCATTTT TTAGGCGTTT ATGCGGGTTT TGGGATAGGG CTTATGCTTT ATCAAGACAA GCCTAATCAA AACGGGAGGA ATTTGATAGT AGGGGGTTAT TCAAGCCCTA ATTTTTTATG GAAATCTTTG ATTGAAGTGG ATTACACTTT TAATGTGGGC GTGAGTTTAA CGCTTTATAG GAAACACCGC TTAGAGATTG GCACAAAATT ACCGATTAGC TATTTGAGGA TGGGAGTAGA AGAGGGAGCG ATTTATCACA ATAAAGAAAA TGATGAACGA TTGTTGATTT CGGCTAACAA CCAGTTCAAA CGATCCAGTT TTTTATTAGT GAATTATGCG TTCATTTTTT GA (2) INFORMATION FOR SEQ ID NO. 9:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 1182 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular (ii) MOLECULA TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE : NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix) SIGN (A) NAME / KEY: different characters (B) PLACEMENT ... 1182

(xi) SEQUENCE DESCRIPTION: SEQ ID NO. 9:

ATGACTTCAG CTTCAAGCCA TTCTTTTAAA GAACAAGATT TTCATATTCC TATCGCTTTC GCTTTTGATA AGAATTATCT CATTCCTGCG GGCGCATGCA TTTATTCCTT GCTAGAAAGC ATCGCTAAAG CCAATAAAAA AATCCGTTAC ACCTTACACG CTTTAGTGGT AGGCTTGAAT GAAGAAGATA AAACAAAACT TAACCAAATC ACAGAGCCTT TTAAAGAATT TGCTGTTTTA GAAGTAAAAG ATATTGAACC TTTTTTAGAC ACTATCCCTA ACCCTTTTGA TGAGGATTTC ACCAAGCGTT TTTCTAAAAT GGTGTTAGTG AAGTATTTTC TAGCGGATTT ATTCCCCAAA TATTCTAAAA TGGTGTGGAG CGATGTGGAT GTTATCTTTT GTAATGAATT TAGCGCTGAT TTCTTAAACA TTAAAGAAGA TGATGAGAAT TATTTTTATG GGGTTTATGA CAAAATATAC

300

360

420

480

540

600

660

720

780

840

900

942

120

180

240

300

360

420

480

147

CCGTATGAAG GCTTTTTTTA TTGCAACTTA ACTTACCAGC GAAAAAATCA ATTTTGTAAA AAAATATTAG AAATCATACG CGCACAAAAA ATAGATAAAG AACCGCAATT GACAGAATTT TGTCGTTCAA AGATCGCGCC ATTAAAAATA GAGTATTGTA TTTTCCCACA CTATTATAGC CTTTCTGAAG AGCATTTAAA GGGCGTGGCC AATGCAATTT ATCATAACAC CATTAAACAA GCCCTAAGAG AACCTATCGT TATACAATAT GACTCTCATC CTTATTTTCA AATCAAGCCT TGGACATATC CTTTTGGTTT GAAAGCGGAT TTATGGCTGA ACGCTTTGGC TAAAACCCCA TTTATGAGCG ATTGGTCTTA TTTGATCACA GGGGGTGGGG GGATAGGTGG AGAAAAATGG CATTACTACC ATGGCATTGC CGCTTATCAT TACTACTTTC CTTTATGGAA AGCAGAAGAA CAGATTGCCC ATGACGCTCT TAAGACATTT TTAAAACATT ATTTTTTGCA CATTCATGAG ATTCCCCAAA ACGCAAGGCGAAGACTATTC AAATACTGCA TTTCAATACC GCTTAAGAGC TTTATTAGTA AAACCCTTAA 10:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 1308 base pairs (B) TYPE: nucleic acid (C) NUMBER OF FIBERS: two (D) TOPOLOGY: circular (ii) MOLECULAR TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE : NO (vi) ORIGINAL SOURCE:

(A) ORGANISM; Helicobacter pylori (Ix) SIGN: (A) NAME / KEY: different characters (B) PLACEMENT 1 ... 1307 (Xi) DESCRIPTION ! SEQUENCE: SEQ ID NO. 10:

TTGATTTTCT TAAAAAAATC TCTTTGCGCG TTGTTAATTT CAGGTTTTTT CATACCACCC TTAATGAAAG CGGCTAGTTT TGTCTATGAC TTGAAGTTTA TGAGCTTTAA TTTCAATCTG GCTTCCCCTC CAAATAACCC CTATTGGAAT AGCCTAACCA AAATGCAAGG TCGTCTCATG CCTCAAATTG GCGTCCAATT AGACAAAAGA CAGGCCTTGA TGTTTGGGGC GTGGTTCATT CAAAATTTGC ACACGCATTA TAGCTATTTC CCTTATTCGT GGGGGGTTAC CATGTATTAC CAATACATAG GGAAAAATTT GAGATTTTTT TTAGGCATTG TGCCACGAAG CTATCAAATA GGGCATTACC CTTTAAGCGC TTTTAAAAAA CTTTTCTGGT TTATAGACCC TACTTTTAGG GGAGGAGCGT TCCAATTCAA ACCGGCTTAT GATCCCAATC GTTGGTGGAA TGGGTGGTTT

540

600

660

720

780

840

900

960

1020

1080

1140

1182

120

180

240

300

360

420

480

148

GAGGGCGTTG TGGATTGGTA TGGGGGGCGT AATTGGAACA ACCAGCCCAA AAAGAAAAAT TACGATTTTG ATCAATTCTT GTATTTTGTT TCTTCAGAAT TTCAGTTTCT TAÄAGGGTAT TTAGGTTTGG GGGGACAGCT TGTCATTTTT CATAACGCCA ACTCTCATAG TATGGGGGAT AACTACCCTT ATGGCGGGAA TTCCTACTTA AAACCAGGCG ATGCAACCCC ACAATGGCCT AATGGCTACC CTTATTTCAG CCAAAAAGAT AACCCACAAG GCGGAGAAAT AGGGAAATAC TCTAACCCTA CCATTTTAGA CAGGGTTTAT TACCATGCTT ATTTAAAAGC AGATTTTAAA AATCTCATGC CTTATATGGA CAATATTTTC ATGACCTTTG GCACGCAGTC GTCTCAAACC CATTATTGCG TGCGTTATGC TAGCGAGTGT AAAAACGCCC GATTTTATAA CAGCTTTGGG GGGGAATTTT ACGCTCAAGC GCAATACAAA GGCTTTGGGA TCTTTAACAG ATACTATTTT TCCAACAAAC CCCAAATGCA TTTTTATGCC ACTTATGGCC AATCCCTTTA TACCGGATTG CCATGGTATA GAGCCCCTAA TTTTGACATG ATAGGGCTTT ATTATCTTTA TAAAAACAAA TGGTTAAGCG TGCGAGCGGA TGCGTTTTTT AGCTTTGTGG GTGGGGGCGA TGGGTACCAT TTGTATGGCA AGGGGGGTAA GTGGTTTGTG ATGTATCAGC AATTTTTAAC CCTAACCATA GACACAAGAG AGTTGATTGA TTTTGTCAAA TCTAAAATCC CTAAATAA (2, INFORMATION FOR SEQ ID NO. 11:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 663 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular (ii) MOLECULAR TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE : NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix) SIGN (A) NAME / KEY: different characters (B) PLACEMENT 1 ... 662

(xi) SEQUENCE DESCRIPTION: SEQ ID NO. 11:

ATGAATAAAA CAACAATTAA AATATTAATG GGCATGGCGT TATTATCATC GCTTCAAGCC GCAGAGGCAG AGCTTGATGA AAAATCAAAA AAACCTAAAT TTGCGGATAG GAATACGTTT TATTTAGGGG TTGGGTATCA GCTTAGCGCG ATCAACACGT CTTTTAGCAC CAGTTCTATA GATAAATCGT ATTTCATGAC CGGCAATGGT TTTGGCGTGG TGTTGGGGGG GAAATTTGTG GCTAAAACGC AAGCTGTAGA GCATGTGGGT TTTCGTTACG GGTTGTTTTA TGATCAGACC TTTTCTTCTC ACAAATCCTA TATTTCTACC TATGGTTTAG AATTTAGCGG TTTGTGGGAC

540

600

660

720

780

840

900

960

1020

1080

1140

1200

1260

1308

120

180

240

300

360

149

GCTTTCAATT CGCCAAAGAT GTTTTTGGGG TTGGAGTTTG GCTTAGGCAT CGCTGGGGCG 420 ACTTACATGC CAGGAGGGGC CATGCATGGG ATTATCGCTC AATATTTAGG CAAAGAAAAT 480 TCGCTTTTCC AATTGCTTGT GAAAGTGGGT TTTCGTTTTG GCTTTTTCCA CAATGAAATC 540 ACCTTTGGGT TGAAATTCCC TGTCATTCCT AACAAAAAAA CGGAAATCGT TGATGGCTTG 600 AGCGCGACCA CTTTATGGCA ACGCTTGCCG GTAGCCTATT TCAATTATAT CTATAATTTT 660 TAG 663 (2) INFORMATION FOR SEQ ID NO. 12:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 351 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular (ii) MOLECULAR TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE : NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) NAME / KEY: different characters (B) LOCATION 1 ... 351 (xi) SEQUENCE DESCRIPTION: SEQUENCE NO. 12:

TTGAATCTCC ATTTTATGAA AGGATTTGTT ATGAGTGGAT TAAGAACATT TAGTTGTGTA 60

GTGGTTTTAT GCGGTGCAAT GGTTAATGTA GCTGTAGCTG GTCCTAAAAT AGAGGCAAGG 120

GGTGAATTAG GCAAATTTGT AGGGGGAGCT GTTGGAAATT TTGTTGGTGA TAAAATGGGC 180

GGATTTGTTG GTGGTGCAAT AGGAGGATAT ATTGGGTCTG AAGTAGGCGA TAGGGTAGAA 240

GATTATATCC GTGGCGTTGA TAGAGAGCCA CAAAACAAAG AACCACAAAC CCCAAGAGAA 300

CCTATCCGTG ATTTTTATGA TTACGGCTAT AGTTTTGGGC ATGCTTGGTG A 351 (2) INFORMATION FOR SEQUENCE NO. 13:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 1311 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular

150 (ii) MOLECULA TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) NAME / KEY: various characters (B) LOCATION 1 ... 1311 (xi) SEQUENCE DESCRIPTION: SEQUENCE NO. 13:

ATGTCAAGGG ATTTTAAATT TGATTCTAAC TATTTAAATG TCAATACCAA TCCTAAATTA 60 GGCCCCGTTT ATACCAATCA AAATTATCCA GGATTTTTTA TCTTTGATCA TTTAAGGCGT 120 TATGTGATGA ACGCTTTTGA GCCTAATTTG AACTTAGTTG TCAATACCAA TAAAGTTAAG 180 CAAACTTTTA ATGTGGGCAT GCGTTTTATG ACAATGGATA TGTTCATTAG ATCCGATCAA 240 AGCACATGCG AAAAAACAGA TATTATCAAT GGGGTGTGCC ACATGCCTCC TTATGTCCTT 300 TCTAAAACGC CTAACAATAA TCAAGAAATG TTTAATAACT ATACAGCGGT ATGGTTGAGC 360 GATAAAATAG AGTTTTTTGA TTCTAAATTG GTGATAACTC CAGGGCTTAG ATACACTTTT 420 TTGAACTATA ACAACAAAGA GCCAGAAAAG CATGATTTTT CCGTATGGAC CAGTAAAAAA 480 CAGCGTCAAA ACGAATGGAG TCCTGCCCTT AATATTGGCT ATAAACCTAT GGAAAATTGG 540 ATATGGTATG CGAACTACCG CCGCAGTTTT ATCCCCCCAC AACACACAAT GGTAGGCATT 600 ACTAGGACTA ATTACAACCA AATTTTTAAT GAAATTGAAG TGGGGCAGCG CTATAGTTAT 660 AAAAATCTAT TGAGTTTTAA CACCAATTAT TTTGTGATTT TTGCCAAGCG TTACTATGCG 720 GGAGGCTATA GCCCACAGCC TGTGGATGCC AGAAGTCAAG GGGTGGAATT GGAATTGTAT 780 TACGCGCCGA TTAGGGGTTT GCAATTCCAT GTGGCTTACA CTTATATTGA TGCGCGCATC 840 ACTTCTAACG CTGATGATAT TGCTTATTAT TTTACAGGCA TTGTCAATAA ACCCTTTGAC 900 ATTAAAGGGA AGCGCTTGCC CTATGTGAGT CCTAACCAAT TCATATTTGA CATGATGTAT 960 ACTTACAAGC ACACGACTTT TGGTATCAGC AGCTATTTTT ATAGCCGCGC TTATAGTTCC 1020 ATGCTCAATC AAGCCAAAGA TCAAACCGTA TGCCTGCCCT TAAACCCAGA ATACACAGGG 1080 GGGTTAAAGT ATGGTTGTAA TTCAGTGGGG TTATTGCCCT TGTATTTTGT GTTGAATGTC 1140 CAAGTAAGCT CAATCTTATG GCAAAGCGGT AGGCATAAAA TCACAGGGAG TTTGCAAATC 1200 AATAACCTTT TTAACATGAA GTATTATTTT AGGGGGATTG GCACAAGCCC TACAGGGAGA 1260 GAACCCGCGC CAGGGAGATC CATTACAGCG TATTTGAATT ATGAGTTTTA A 1311

(2) INFORMATION FOR SEQUENCE NO. 14:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 2304 base pairs (B) TYPE: nucleic acid

151 (C) FIBER NUMBER: two (D) TOPOLOGY: circular (ii) MOLECULAR TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) NAME / KEY: various characters (B) LOCATION 1 ... 2304 (xi) SEQUENCE DESCRIPTION: SEQUENCE NO. 14:

ATGAAAAGAA TTTTAGTTTC TTTGGCTGTT TTGAGTCATA GCGCGCATGC TGTCAAAACT 60 CATAATTTGG AAAGGGTGGA AGCTTCAGGG GTGGCTAACG ATAAAGAAGC GCCTTTAAGC 120 TGGAGGAGCA AGGAAGTTAG AAATTATATG GGTTCTCGCA CGGTGATTTC TAACAAGCAA 180 CTCACTAAAA GCGCCAATCA AAGCATTGAA GAAGCTTTGC AAAATGTGCC AGGCGTGCAT 240 ATTAGAAACT CTACCGGTAT TGGAGCTGTG CCTAGCATTT CCATTAGGGG GTTTGGTGCT 300 GGAGGCCCAG GGCATTCTAA TACGGGAATG ATTCTAGTCA ATGGGATTCC TATTTATGTC 360 GCGCCCTATG TTGAAATTGG CACGGTTATT TTTCCTGTAA CCTTTCAGTC TGTGGATAGA 420 ATCAGCGTAA CTAAGGGTGG GGAGAGCGTG CGTTATGGCC CTAACGCTTT TGGCGGTGTG 480 ATCAACATCA TCACCAAAGG CATTCCTACC AATTGGGAAA GTCAGGTGAG CGAGAGGACC 540 ACTTTTTGGG GCAAGTCTGA AAACGGGGGC TTTTTCAATC AAAATTCTAA AAACATTGAT 600 AAAAGCTTAG TTAATAACAT GCTTTTTAAC ACCTATTTAA GAACGGGGGG TATGATGAAT 660 AAGCATTTTG GAATCCAAGC TCAAGTCAAT TGGCTCAAAG GGCAAGGGTT TAGATACAAC 720 AGCCCTACGG ATATTCAAAA TTACATGTTA GATTCATTGT ATCAAATCAA TGATAGCAAT 780 AAAATCACCG CTTTTTTTCA ATATTATAGT TATTTCTTGA CAGACCCTGG ATCTTTAGGC 840 ATAGCCGCTT ACAATCAAAA TCGTTTTCAA AACAACCGCC CCAATAACGA TAAAAGCGGG 900 AGAGCGAAGC GATGGGGAGC TGTGTATCAA AACTTTTTTG GGGACACGGA TAGGGTAGGG 960 GGGGATTTCA CTTTTAGCTA CTATGGGCAT GACATGTCAA GGGATTTTAA ATTTGATTCT 1020 AACTATTTAA ATGTCAATAC CAATCCTAAA TTAGGCCCCG TTTATACCAA TCAAAATTAT 1080 CCAGGATTTT TTATCTTTGA TCATTTAAGG CGTTATGTGA TGAACGCTTT TGAGCCTAAT 1140 TTGAACTTAG TTGTCAATAC CAATAAAGTT AAGCAAACTT TTAATGTGGG CATGCGTTTT 1200 ATGACAATGG ATATGTTCAT TAGATCCGAT CAAAGCACAT GCGAAAAAAC AGATATTATC 1260 AATGGGGTGT GCCACATGCC TCCTTATGTC CTTTCTAAAA CGCCTAACAA TAATCAAGAA 1320 ATGTTTAATA ACTATACAGC GGTATGGTTG AGCGATAAAA TAGAGTTTTT TGATTCTAAA 1380 TTGGTGATAA CTCCAGGGCT TAGATACACT TTTTTGAACT ATAACAACAA AGAGCCAGAA 1440 AAGCATGATT TTTCCGTATG GACCAGTAAA AAACAGCGTC AAAACGAATG GAGTCCTGCC 1500 CTTAATATTG GCTATAAACC TATGGAAAAT TGGATATGGT ATGCGAACTA CCGCCGCAGT 1560

152

TTTATCCCCC CACAACACAC AATGGTAGGC ATTACTAGGA CTAATTACAA CCAAATTTTT 1620 AATGAAATTG AAGTGGGGCA GCGCTATAGT TATAAAAATC TATTGAGTTT TAACACCAAT 1680 TATTTTGTGA TTTTTGCCAA GCGTTACTAT GCGGGAGGCT ATAGCCCACA GCCTGTGGAT 1740 GCCAGAAGTC AAGGGGTGGA ATTGGAATTG TATTACGCGC CGATTAGGGG TTTGCAATTC 1800 CATGTGGCTT ACACTTATAT TGATGCGCGC ATCACTTCTA ACGCTGATGA TATTGCTTAT 1860 TATTTTACAG GCATTGTCAA TAAACCCTTT GACATTAAAG GGAAGCGCTT GCCCTATGTG 1920 AGTCCTAACC AATTCATATT TGACATGATG TATACTTACA AGCACACGAC TTTTGGTATC 1980 AGCAGCTATT TTTATAGCCG CGCTTATAGT TCCATGCTCA ATCAAGCCAA AGATCAAACC 2040 GTATGCCTGC CCTTAAACCC AGAATACACA GGGGGGTTAA AGTATGGTTG TAATTCAGTG 2100 GGGTTATTGC CCTTGTATTT TGTGTTGAAT GTCCAAGTAA GCTCAATCTT ATGGCAAAGC 2160 GGTAGGCATA AAATCACAGG GAGTTTGCAA ATCAATAACC TTTTTAACAT GAAGTATTAT 2220 TTTAGGGGGA TTGGCACAAG CCCTACAGGG AGAGAACCCG CGCCAGGGAG ATCCATTACA 2280 GCGTATTTGA ATTATGAGTT TTAA 2304 (2) INFORMATION FOR SEQ ID NO. 15:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 348 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular (ii) MOLECULA TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE : NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) NAME / KEY: different characters (B) LOCATION 1 ... 348 (xi) SEQUENCE DESCRIPTION: SEQUENCE NO. 15:

TTGCACCCTC TATGCGCACA CGGCCAATGT GGAAGCGAAG CGATTGCGTG TTTAGAAGCC 60 ATTAGCGTGG GGATTGTGCC TGTTATCGCT AATAGCCCTT TAAGCGCGAC CAGGCAATTC 120 GCGCTAGATG AACGATCGTT ATTTGAGCCT AATAACGCTA AAGATTTGAG CGCTAAAATA 180 GACTGGTGGT TAGAAAACAA ACTTGAAAGA GAAAGAATGC AAAACGAATA CGCTAAAAGC 240 GCTTTAAACT ACACTTTAGA AAATTCAGTC ATTCAAATTG AAAAAGTTTA TGAAGAAGCG 300 ATCAAAGATT TTAAAAACAA CCCCAACCTC TTTAAAACCT TATCGTAA 348

153 (2) INFORMATION FOR SEQUENCE NO. 16:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 1170 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular (ii) MOLECULA TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE : NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) NAME / KEY: various characters (B) LOCATION 1 ... 1170 (xi) SEQUENCE DESCRIPTION: SEQUENCE NO. 16:

ATGGTTATTG TTTTAGTCGT GGATAGCTTT AAAGACACCA GTAATGGCAC TTCTATGACA 60 GCGTTTCGTT TTTTTGAAGC GCTGAAAAAA AGAGGGCATG CGATGAGAGT GGTCGCCCCT 120 CATGTGGATA ATTTAGGGAG TGAAGAAGAG GGGTATTACA ACCTTAAAGA GCGCTATATC 180 CCCCTAGTTA CAGAAATTTC ACACAAGCAA CACATTCTTT TTGCCAAACC GGATGAAAAA 240 ATTCTACGAA AGGCTTTTAA GGGAGCGGAT ATGATCCATA CTTACTTGCC TTTTTTGCTA 300 GAAAAAACAG CCGTAAAAAT CGCGCGAGAA ATGCGAGTGC CTTATATTGG CTCTTTCCAT 360 TTACAGCCAG AGCATATTTC TTATAACATG AAATTGGGGC ÄATTTTCTTG GCTAAATACC 420 ATGCTTTTTT CATGGTTTAA ATCTTCGCAT TACCGCTATA TCCACCATAT CCATTGCCCA 480 TCAAAATTCA TTGTAGAAGA ATTGGAAAAA TACAACTATG GAGGAAAAAA ATACGCTATC 540 TCTAACGGCT TTGATCCCAT GTTTAAGTTT GAGCACCCGC AAAAAAGCCT TTTTGACACC 600 ACGCCCTTTA AAATCGCTAT GGTAGGGCGC TATTCTAATG AAAAAAATCA AAGCGTTCTC 660 ATTAAAGCGG TTGCTTTAAG CCGATACAAA CAAGACATTG TATTATTACT CAAAGGCAAG 720 GGGCCTGATG AGAAAAAAAT CAAACTTCTA GCCCAAAAAC TAGGCGTAAA AACGGAGTTT 780 GGGTTTGTCA ATTCCCATGA ATTGTTAGAG ATTTTAAAAA CTTGCACCCT CTATGCGCAC 840 ACGGCCAATG TGGAAAGCGA AGCGATTGCG TGTTTAGAAG CCATTAGCGT GGGGATTGTG 900 CCTGTTATCG CTAATAGCCC TTTAAGCGCG ACCAGGCAAT TCGCGCTAGA TGAACGATCG 960 TTATTTGAGC CTAATAACGC TAAAGATTTG AGCGCTAAAA TAGACTGGTG GTTAGAAAAC 1020 AAACTTGAAA GAGAAAGAAT GCAAAACGAA TACGCTAAAA GCGCTTTAAA CTACACTTTA 1080 GAAAATTCAG TCATTCAÄAT TGAAAAAGTT TATGAAGAAG CGATCAAAGA TTTTAAAAAC 1140 AACCCCAACC TCTTTAAAAC CTTATCGTAA 1170

154 (2) INFORMATION FOR SEQUENCE NO. 17:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 939 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular (ii) MOLECULA TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE : NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (Ix) SIGN: (A) NAME / KEY: different characters (B) PLACEMENT 1 ... 939 (Xi) DESCRIPTION i SEQUENCES: SEQ ID NO. 17:

TTGGCTTCTT ACGGGTTTTT TTTAGGAGCG TTGTTTATTT TAGCGAGCGG GATCGTGTGC 60 TTACAGACTG CCGGTAATCC CTTTGTAACC TTGCTTTCTA AAGGTAAAGA AGCCAGAAAC 120 TTGGTTTTAG TCCAGGCGTT CAATTCGCTT GGCACGACTT TAGGGCCTAT TTTTGGGAGC 180 TTGTTGATTT TTAGCGCGAC CAAAACGAGC GATAATTTAA GCCTGATAGA CAAGTTAGCG 240 GACGCTAAAA GCGTTCAAAT GCCTTATTTG GGTTTAGCGG TGTTTTCGCT TCTTTTAGCG 300 CTTGTGATGT ATCTTTTAAA ATTGCCTGAT GTGGAAAAAG AAATGCCCAA AGAAACGACG 360 CAAAAAAGCC TGTTTTCGCA CAAACACTTT GTTTTTGGGG CTTTAGGGAT CTTTTTCTAT 420 GTGGGGGGAG AAGTGGCGAT TGGATCATTC TTGGTGCTAA GCTTTGAAAA GCTTTTGAAT 480 TTAGACGCTC AATCAAGCGC GCATTACTTG GTGTATTATT GGGGCGGCGC GATGGTAGGG 540 CGTTTCTTAG GCAGCGCTTT GATGAATAAA ATCGCTCCTA ATAAATACCT GGCTTTCAAC 600 GCCTTAAGCT CTATCATTCT TATCGCTTTG GCTATTCTTA TTGGAGGCAA GATCGCTTTA 660 TTCGCTCTGA CTTTTGTGGG CTTTTTCAAC TCTATCATGT TCCCTACAAT CTTTTCTTTG 720 GCTACGCTCA ATTTAGGGCA TCTCACTTCT AAGGCTTCTG GAGTGATTAG CATGGCGATT 780 GTGGGAGGGG CGTTAATCCC CCCCATTCAA GGCGTGGTTA CAGACATGCT CACAGCAACC 840 GAATCGAATC TGCTCTACGC TTATAGCGTG CCGTTGTTGT GCTATTTTTA TATCCTCTTC 900 TTTGCACTTA AGGGGTATAA ACAAGAAGAA AACTCCTAA 939

(2) INFORMATION FOR SEQUENCE NO. 18:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 1224 base pairs

155 (ii) (iii) (iv) (vi) (ix) (xi) (B) TYPE: nucleic acid (C) NUMBER OF FIBERS: two (D) TOPOLOGY: circular

MOLECULA TYPE: DNA (genomic)

HYPOTHETICAL: NO

ANTI-SENSE: NO

ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori

SIGN:

(A) TITLE / KEY: various characters (B) LOCATION 1 ... 1224

SEQUENCE DESCRIPTION: SEQ. 18:

ATGCAAAAAA CTTCTAACAC TTTAGCGCTG GGGAGTTTGA CGGCGCTATT CTTTCTAATG 60 GGTTTTATCA CGGTTTTAAA CGACATTTTG ATCCCGCATT TAAAGCCCAT TTTTGACTTG 120 ACCTATTTTG AAGCTTCGCT CATTCAATTT TGCTTTTTTG GGGCGTATTT CATCATGGGG 180 GGAGTCTTTG GGAACGTGAT CAGTAAAATC GGCTACCCTT TTGGCGTGGT GCTTGGTTTT 240 GTGATCACAG CGAGCGGGTG CGCGTTGTTT TATCCGGCGG CGCATTTTGG CTCTTACGGG 300 TTTTTTTTAG GAGCGTTGTT TATTTTAGCG AGCGGGATCG TGTGCTTACA GACTGCCGGT 360 AATCCCTTTG TAACCTTGCT TTCTAAAGGT AAAGAAGCCA GAAACTTGGT TTTAGTCCAG 420 GCGTTCAATT CGCTTGGCAC GACTTTAGGG CCTATTTTTG GGAGCTTGTT GATTTTTAGC 480 GCGACCAAAA CGAGCGATAA TTTAAGCCTG ATAGACAAGT TAGCGGACGC TAÄAAGCGTT 540 CAAATGCCTT ATTTGGGTTT AGCGGTGTTT TCGCTTCTTT TAGCGCTTGT GATGTATCTT 600 TTAAAATTGC CTGATGTGGA AAAAGAAATG CCCAAAGAAA CGACGCAAAA AAGCCTGTTT 660 TCGCACAAAC ACTTTGTTTT TGGGGCTTTA GGGATCTTTT TCTATGTGGG GGGAGAAGTG 720 GCGATTGGAT CATTCTTGGT GCTAAGCTTT GAAAAGCTTT TGAATTTAGA CGCTCAATCA 780 AGCGCGCATT ACTTGGTGTA TTATTGGGGC GGCGCGATGG TAGGGCGTTT CTTAGGCAGC 840 GCTTTGATGA ATAAAATCGC TCCTAATAAA TACCTGGCTT TCAACGCCTT AAGCTCTATC 900 ATTCTTATCG CTTTGGCTAT TCTTATTGGA GGCAAGATCG CTTTATTCGC TCTGACTTTT 960 GTGGGCTTTT TCAACTCTAT CATGTTCCCT ACAATCTTTT CTTTGGCTAC GCTCAATTTA 1020 GGGCATCTCA CTTCTAAGGC TTCTGGAGTG ATTAGCATGG CGATTGTGGG AGGGGCGTTA 1080 ATCCCCCCCA TTCAAGGCGT GGTTACAGAC ATGCTCACAG CAACCGAATC GAATCTGCTC 1140 TACGCTTATA GCGTGCCGTT GTTGTGCTAT TTTTATATCC TCTTCTTTGC ACTTAAGGGG 1200 TATAAACAAG AAGAAAACTC CTAA 1224

(2) INFORMATION FOR SEQUENCE NO. 19:

(i) SEQUENCE CHARACTERISTICS

156 (A) LENGTH: 378 base pairs (B) TYPE: nucleic acid (C) NUMBER OF FIBERS: two (D) TOPOLOGY: circular (ii) MOLECULAR TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI- SENSE: NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix) SIGN: (A) NAME / KEY: different characters (B) PLACEMENT 1 ... 378

(xi) SEQUENCE DESCRIPTION: SEQ ID NO. 19:

ATGAATAAAA TCGCTCCTAA TAAATACCTG GCTTTCGGCG CCTTAAGCTC TATCATTCTT ATCGCTTTGG CTATTCTTAT TGGAGGCAAG ATCGCTTTAT TCGCTCTGAC TTTTGTGGGC TTTTTCAACT CTATCATGTT CCCTACAATC TTTTCTTTGG CTACGCTCAA TTTAGGCATC TCACTTCTAA TGGCTTCTGG AGTGATTAGC ATGGCGATTG TGGGAGGGGC GTTAATCCCC CCCATTCAAG GCGTGGTTAC AGACATGCTC ACAGCAACCG AATCGAATCT GCTCTACGCT TATAGCGTGC CGTTGTTGTG CTATTTTTAT ATCCTCTTCT TTGCACTTAA GGGGTATAAA CAAGAAGAAA ACTCCTAA (2) INFORMATION FOR SEQ ID NO. 20:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 993 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular (ii) MOLECULA TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE : NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori

120

180

240

300

360

378

157 (ix) SIGN:

(A) TITLE / KEY: various characters (B) LOCATION 1 ... 993 (xi) SEQUENCE DESCRIPTION: SEQUENCE NO. 20:

TTGAAAAAAA TATTACCGGC TTTGTTAATG GGGTTTGTGG GATTGAATGC TAGTGATCGT 60

TTGTTAGAAA TCATGCGCCT TTATCAAAAA CAAGGCTTGG AAGTGGTGGG TCAAAAATTG 120

GATTCTTATT TAGCGGATAA GTCTTTTTGG GCAGAAGAGC TTCAAAACAA GGACACGGAT 180

TTTGGCTATT ATCAAAACAA GCAGTTTTTA TTTGTGGCGG ATAAATCCAA GCCCAGTTTG 240

GAGTTTTATG AAATAGAAAA TAACATGCTT AAAAAAATCA ACAGCTCTAA AGCCCTTGTA 300

GGCTCTAAAA AGGGCGATAA AACTTTAGAG GGCGATTTGG CCACGCCTAT TGGAGTGTAT 360

CGTATCACGC AGAAATTAGA GCGTTTGGAT CAATATTATG GCGTTTTGGC TTTTGTAACG 420

AATTACCCTA ATTTGTATGA CACTTTGAAA AAACGCACCG GGCATGGCAT TTGGGTGCAT 480

GGAATGCCTT TAAATGGCGA TAGGAATGAA TTGAACACTA AGGGTTGCAT TGCGATTGAA 540

AACCCTATTC TAAGCTCTTA TGACAAAGTG TTAAAAGGCG AAAAAGCGTT CCTTATCACT 600

TATGAAGACA AGTTTTCCCC TAGCACTAAA GAAGAATTGA GCATGATTTT AAGCTCCCTT 660

TTCCAATGGA AAGAAGCTTG GGCTAGGGGC GATTTTGAAC GCTACATGCG TTTTTATAAC 720

CCCAATTTCA CTCGCTATGA CGGCATGAGT TTTAACGCTT TTAAAGAGTA TAAAAAAAGG 780

GTGTTTGCAA AAAATGAAAA AAAGAATATC GCTTTTTCCT CTATCAATGT GATCCCTTAC 840

CCCAACTCTC AAAACAAACG CTTGTTTTAT GTGGTATTTG ACCAAGATTA CAAAGCCTAC 900

CAGCAAAACA AGCTCTCTTA TAGCTCCAAT TCTCAAAAAG AACTCTATGT AGAGATTGAA 960

AACAATCAAG CGTCTATTAT AATGGAAAAA TAA 993 (2) INFORMATION FOR SEQUENCE NO. 21:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 510 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular (ii) MOLECULAR TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE : NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) TITLE / KEY: different characters

158 (B) LOCATION 1 ... 510 (xi) SEQUENCE DESCRIPTION: Seq. 21:

TTGTTTGAGA AATGGATTGG TCTGACCTTA CTCCTTAGTT CCTTAGGCTA TCCATGCCAA AAGGTAAGTA TTAGTTTCAA GCAATACGAA AATCTTATCC ATATCCATCA AAAAGGTTGC AACAATGAAG TGGTGTGCAG AACGCTCATC TCTATCGCTT TACTAGAAAG CTCTCTAGGG TTGAACAACA AGCGAGAAAA ATCCCTTAAA GACACTTCTT ACTCCATGTT CCATATCACC TTAAACACCG CTAAAAAGTT CTACCCTACC TATTCTAAAA CGCTCCTCAA AACCAAATTG TTAAATGATG TGGGTTTTGC GATCCAATTA GCCAAACAAA TTTTAAÄAGA AAATTTTGAT TATTACCACC AAAAACACCC CAACAAAAGC GTGTATCAAT TAGTACAAAT GGCCATAGGC GCTTACAATG GGGGAATGAA ACACAACCCT AATGGCGCTT ACATGAAGAA GTTTCGTTGC ATTTATTCTC AAGTGCGATA CAACGAATAA (2) INFORMATION FOR SEQUENCE NO. 22:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 648 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular (ii) MOLECULAR TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE : NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) NAME / KEY: various characters (B) LOCATION 1 ... 648 (xi) SEQUENCE DESCRIPTION: Sequence no. 22:

ATGAAAAAAC CCTACAGAAA GATTTCTGAT TATGCGATCG TGGGTGGTTT GAGCGCGTTA GTGATGGTAA GCATTGTGGG GTGTAAGAGC AATGCCGATG ACAAACCAAA AGAGCAAAGC TCTTTAAGTC AAAGCGTTCA AAAAGGCGCG TTTGTGATTT TAGAAGAGCA AAAGGATAAA TCTTACAAGG TTGTTGAAGA ATACCCCAGC TCAAGAACCC ACATTGTAGT GCGCGATTTG CAAGGCÁÁTG ÁACGCGTGTT GAGCAATGAA GAGATTCAAA AGCTCATCAA AGAAGAAGAA GCCAAAATTG ATAACGGCAC GAGCAAGCTT GTCCAGCCTA ATAATGGAGG GAGTAATGAA GGATCAGGCT TTGGCTTGGG AAGCGCGATT TTAGGGAGCG CGGCGGGGGC GATTTTAGGG

120

180

240

300

360

420

480

510

120

180

240

300

360

420

159

AGTTATATTG GCAATAAGCT TTTTAATAAC CCTAATTATC AGCAAAACGC CCAACGGACC 480

TACAAATCCC CACAAGCTTA CCAACGCTCT CAAAATTCTT TTTCTAAAAG CGCACCCAGC 540

GCTTCAAGCA TGGGCACAGC GAGTAAGGGA CAGAGCGGGT TTTTTGGCTC TAGTAGGCCT 600

ACTAGTTCGC CTGCAATAAG CTCTGGGACA AGGGGCTTTA ACGCATAA 648 (2) INFORMATION FOR SEQUENCE NO. 23:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 762 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular (ii) MOLECULA TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE : NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) NAME / KEY: various characters (B) LOCATION 1 ... 762 (xi) SEQUENCE DESCRIPTION: Sequence no. 23:

TTGAAAACTC TATTTAGTGT TTATCTCTTT TTGTCGTTGA ATCCACTCTT TTTAGAAGCT 60 AAAGAAATCA CTTGGTCTCA ATTCTTGGAA AATTTTAAAA ACAAGAATGA AGACGACAAA 120 CCTAAACCCC TAACCATTGA CAAAAACAAT GAAAAACAGC AAATCCTAGA CAAAAACCAG 180 CAAATCTTAA AAAGGGCTTT AGAAAAAAGC CTTAAATTTT TCTTTATTTT TGGATACAAC 240 TATTCGCAAG CCGCTTATTC AACCACTAAT CAAAACTTGA CTCTTACGGC GAATAGCATA 300 GGGTTTAACA CCGCTACAGG CTTGGAGCAT TTTTTAAGAA ACCACCCTAA AGTCGGTTTT 360 AGAATCTTTA GCGTCTATAA CTATTTCCAT TCCGTTTCGC TCTCCCAGCC TCAAATCCTA 420 ATGGTGCAAA ATTACGGAGG CGCGTTAGAT TTTTCTTGGA TTTTTGTGGA TAAAAAAACC 480 TATCGCTTTA GGAGTTATTT AGGAATCGCT TTAGAGCAAG GGGTGTTGTT AGTGGATACG 540 ATTAAAACCG GCTCTTTCAC AACCATCATC CCAAGAACCA AGAAAACCTT TTTTCAAGCC 600 CCTTTGCGTT TTGGTTTTAT CGTGGATTTT ATCGGCTATT TGTCTTTGCÄ ATTAGGGATT 660 GAAATGCCCT TAGTGAGGAA TGTTTTTTAC ACCTACAATA ACCATCAAGA AAGATTCAAA 720 CCACGATTTA ACGCTAATCT TTCTTTAATC GTTTCGTTTT AG 762 (2) INFORMATION FOR SEQ ID NO. 24

160 (i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 1011 base pairs (B) TYPE: nucleic acid (C) NUMBER OF FIBERS: two (D) TOPOLOGY: circular (ii) MOLECULAR TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE : NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) NAME / KEY: various characters (B) LOCATION 1 ... 1011 (xi) SEQUENCE DESCRIPTION: Sequence no. 24:

TTGTTTTTCA AATTTATTTT ATGTTTATCA TTAGGAATAT TTGCATGGGC AAAAGAGGTC 60

ATTCCCACCC CTTCAACCCC ATTAACGCCC TCTAAACGCT ATTCTATCAA TTTGATGACT 120

GAAAATGATG GTTATATCAA TCCTTACATT GATGAGTATT ACACGGCAGG CAATCAAATA 180

GGCTTTTCTA CTAAAGAGTT TGATTTTTCT AAAAATAAAG CGATGAAATG GTCTTCGTAT 240

TTAGGGTTTT TCAATAAAAG CCCTAGGGTT ACTCGTTTTG GCATTTCTCT CGCCCAAGAC 300

ATGTATACCC CCTCACTTGC AAACAGAAAA CTGGTGCATT TGCATGACAA CCACCCTTAT 360

GGGGGGTATT TGAGGGTGAA TTTGAACGTG TATAACCGCC ATCAAACTTT CATGGAGTTA 420

TTCACGATTT CTTTAGGCAC GACAGGGCAA GATTCTTTGG CCGCTCAAAC GCAGCGTCTC 480

ATTCATAAAT GGGGTCATGA TCCCCAATTT TATGGCTGGA ACACGCAGCT CAAAAACGAA 540

TTTATCTTTG AACTGCACTA CCAATTGCTT AAAAAAGTCC CCCTTTTAAA GACTCGTTTT 600

TTTTCTATGG AGTTGATGCC TGGGTTTAAT GTGGAACTGG GTAATGCGAG GGATTATTTC 660

CAACTCGGCT CGCTCTTTAG GGCTGGGTAT AACTTGGACG CTGATTATGG GGTCAATAAG 720

GTCAATACCG CTTTTGATGG GGGCATGCCT TATAGCGATA AGTTTTCCAT CTATTTTTTT 780

GCAGGGGCTT TTGGGCGCTT CCAACCCCTT AACATCTTCA TTCAAGGCAA TAGCCCTGAA 840

ACTAGGGGCA TTGCCAATTT GGAATACTTT GTTTATGCCA GTGAAATAGG AGCGGCTATG 900

ATGTGGCGTA GCCTCAGGGT GGCTTTTACA ATCACTGATA TTAGTAAAAC CTTTCAGTCC 960

CAGCCTAAGC ACCATCAGAT CGGCACCTTA GAATTGAATT TCGCCTTTTG A 1011 (2) INFORMATION FOR SEQUENCE NO. 25:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 327 base pairs (B) TYPE: nucleic acid

161 (C) NUMBER OF FIBERS: two (D) TOPOLOGY: circular (ii) MOLECULA TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix) SIGN: (A, NAME / KEY: different characters (B) PLACEMENT 1 ... 327

(xi) SEQUENCE DESCRIPTION: SEQ ID NO. 25:

ATGAAACCAA TCTTTAGCCT CTTTTTCCTC CTTATTGTTT TAAAAGCGCA CCCCATAAAC CCCTTATTAG AGCCGTTATA TTTCCCCAGT TACACGCAAT TTTTAGATTT AGAACCTCAT TTTGTCATTA AAAAAAAGCG CGCTTACAGG CCTTTTCAAT GGGGGAACAC TATTATTATC AAACGCCATG ATTTAGAAGA GCGCCAGAGC AACCAACCAA GCGATATTTT CCGCCAGAAC GCTGAAATCA ATGTGTCTTC TCAAACTTTT TTAAGAGGAA TCAGCAGCGC TTCTTCACGC ATAGTGATCG ATTCGGTCGC TCAGTAA

120

180

240

300

327 (2) INFORMATION FOR SEQUENCE NO. 26:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 588 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular (ii) MOLECULAR TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE : NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) TITLE / KEY: different characters

162 (B) LOCATIONS 1 ... 588 (xi) SEQUENCE DESCRIPTION: SEQ ID NO. 26:

ATGAGCAATA ACCCCTTTAA AAAAGTGGGC ATGATCAGCT CTCAAAACAA TAACGGCGCT TTGAACGGGC TTGGCGTGCA AGTGGGTTAT AAACAATTCT TTGGCGAAAG CAAAAGATGG GGGTTAAGGT ATTATGGTTT CTTTGATTAC AACCACGGCT ATATCAAATC CAGCTTTTTT AATTCTTCTT CTGATATATG GACTTATGGC GGTGGGAGCG ATTTGTTAGT GAATTTTATC AACGATAGCA TCACAAGAAA GAACAACAAG CTTTCTGTGG GTCTTTTTGG TGGTATCCAA CTAGCAGGGA CTACATGGCT TAATTCTCAA TACATGAATT TAACAGCGTT CAATAACCCT TACAGCGCGA AAGTCAATGC TTCCAATTTC CAATTTTTGT TCAATCTCGG CTTGAGGACG AATCTCGCTA CAGCTAAGAA AAAAGACAGC GAACGTTCCG CGCAACATGG CGTTGAACTG GGCATTAAAA TCCCTACCAT TAACACCAAT TATTATTCTT TTCTAGGCAC TAAGCTAGAA TACAGAAGGC TTTATAGCGT GTATCTCAAT TATGTGTTTG CTTATTAA (2) SEQ ID NO. 27:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 684 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular (ii) MOLECULA TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE : NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) NAME / KEY: various characters (B) LOCATION 1 ... 684 (xi) SEQUENCE DESCRIPTION: Sequence no. 27:

GTGCGTTTTG GTAAAATTGA TTATTTGAAC ATGCTCCCTT TTGATGTGTT TATCAAATCC TACCCCACCC CTTGTTATTT CAAACAATTC TTACGGCTTA AAAAAACCTA CCCCTCCAAA CTCAATGAGA GTTTTTTATT CAGGCGCATT GATGCGGGGT TTATTTCTTC TATCGCTGGC TATCCATTCG CTCTTTGTTC TTATTCTCTA GGCATTGTCG CTTATAAGGA AGTTTTAAGC GTGTTGGTTG TAAATAGAGA AAACGCTTTT GACAAAGAAA GCGCTTCTTC AAACGCCCTC TCTAAAGTGT TAGGGTTAAA AGGCGAGGTC TTAATCGGCA ATAAAGCGCT GCAATTTTAT

120

180

240

300

360

420

480

540

588

120

180

240

300

360

163

TATTCCAACC CTAAAAAAGA TTTTATAGAT TTAGCCGCTC TGTGGTATGA AAAAAAACGC TTGCCGTTTG TTTTTGGGCG TCTGTGCTAT TATCAAAACA AGGATTTTTA CAAACGCTTG TCTTTAGCCT TCAAACATCA AAAAACAAAA ATCCCTCACT ACATCCTTAA AGAAGCCGCT TTGAAAACCA ACTTGAAACG CCAAGATATT CTAAACTACT TGCAAAAAAT TTACTACACT TTAGGCAAAA AGGAACAATC AGGCCTTAAA GCGTTCTATC GTGAATTGTT GTTCAAACGC ATCCAAAAAC CCAAGCGGTT Ttag (2) INFORMATION FOR SEQ ID NO. 28:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 918 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular (ii) MOLECULAR TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE : NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) NAME / KEY: various characters (B) LOCATION 1 ... 918 (xi) SEQUENCE DESCRIPTION: Sequence no. 28:

ATGGGTAGAA TTGAATCAAA AAAGCGTTTG AÄAGCACTCA TTTTTTTAGC GAGTTTGGGG GTGTTGTGGG GCAATGCGGC TGAAAAAACG CCTTTTTTTA AAACTAAAAA CCACATTTAT TTGGGTTTTA GGCTAGGCAC AGGGGCTACT ACGCGCACAA GCATGTGGCA ACAAGCCTAT AAAGACAACC CCACTTGCCC TAGCAGCGTG TGTTATGGCG AGAAATTAGA AGCCCATTAT AAGGGGGGTA AAAACTTATC TTATACCGGG CAAATAGGCG ATGAAATAGC TTTTGATAAA TACCATATTT TAGGCTTAAG GGTGTGGGGG GATGTAGAAT ACGCTAAGGC TCAATTAGGT CAAAAAGTGG GGGGTAACAC CCTTTTATCC CAAGCGAATT ATAACCCAAG CGCGATTAAA ACCTACGATC CTACTTCAAA CGCTCAAGGC TCTTTAGTTT TGCAAAAAAC CCCAAGCCCC CAAGATTTCC TTTTCAATAA CGGGCATTTC ATGGCGTTTG GTTTGAACGT GÄACATGTTT GTCAATCTCC CTATAGACAC CCTTTTAAAA CTCGCTTTÄA AAACGGAAAA AATGCTGTTT TTTAAAATAG GCGTGTTTGG TGGGGGTGGG GTGGAATACG CAATCTTGTG GAGTCCTCAA TATAAAAATC AAAATACCCA TCAAGACGAT AAATTTTTTG CCGCAGGTGG GGGGTTTTTT GTGAATTTTG GAGGCTCTTT GTATATAGGC AAGCGCAACC GCTTCAATGT GGGGCTAAAA ATCCCTTATT ATAGCTTGAG CGCGCAAAGT TGGAAAAATT TTGGCTCTAG CAATGTGTGG

420

480

540

600

660

684

120

180

240

300

360

420

480

540

600

660

720

780

840

164

CAGCAACAAA CGATCCGACA AAACTTCAGC GTTTTTAGGA ATAAAGAAGT TTTTGTCAGC TACGCGTTCT TGTTTTAG (2) INFORMATION FOR SEQUENCE NO. 29:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 777 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular (ii) MOLECULAR TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE : NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) NAME / KEY: various characters (B) LOCATION 1 ... 777 (xi) SEQUENCE DESCRIPTION: Sequence £. 29:

ATGTTTTTAA GATCATACCC AAAGCTTAGA TACGCTTTAT GTTTACCCCT ACTCACTGAG ACTTGCTATA GCGAGGAGCG CACTTTAAAT AAGGTTACCA CCCAAGCTAA AAGGATTTTC ACTTACAATA ATGAGTTTAA GGTTACTTCT AAAGAATTGG ATCAACGCCA AAGCAATGAA GTCAAAGACC TGTTTAGGAC TAACCCTGAT GTGAATGTGG GCGGAGGGAG CGTGATGGGG CAGAAAATCT ACGTGAGAGG CATTGAAGAC AGGCTTTTAA GGGTTACGGT GGATGGGGCT GCGCAAAATG GCAACATCTA CCACCACCAA GGCAACACCG TGATTGACCC TGGCATGCTC AAAAGCGTGG AAGTTACTAA AGGCGCGGCG AATGCGAGCG CGGGGCCAGG AGCGATCGCG GGAGTGATTA AAATGGAGAC TAAAGGAGCG GCTGATTTTA TCCCTAGGGG GAAAAATTAT GCAGCGAGTG GGGCGGTGAG TTTTTATACC AATTTTGGGG ACAGAGAGAC TTTTAGATCG GCCTATCAAA GCGCGCATTT TGATATTATC GCTTACTACA CGCACCAAAA TATTTTCTAT TATAGGAGCG GCGCCACAGT GATGAAAAAC CTTTTCAAAC CCACACAAGC CGATAAAGAG CCAGGAACTC CCAGCGAGCA AAACAACGCT TTGATTAAAA TGAATGGCTA TTTGAGCGAC AGAGACACGC TCACTTTCAG CTGGAACATG ACACGAGATA ACGCCACACG CCTTTAA (2) INFORMATION FOR SEQ ID NO. 30:

900

918

120

180

240

300

360

420

480

540

600

660

720

777 (i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 579 base pairs

165 (B) TYPE: nucleic acid (C) NUMBER OF FIBERS: two (D) TOPOLOGY: circular (ii) MOLECULAR TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE :

(A) ORGANISM: Helicobacter pylori (ix)

(A) NAME / KEY: various characters (B) LOCATION 1 ... 579 (xi) SEQUENCE DESCRIPTION: Sequence no. 30:

ATGTTTTTAA GATCATACCC AAAGCTTAGA TACGCTTTAT GTTTACCCCT ACTCACTGAG 60

ACTTGCTATA GCGAGGAGCG CACTTTAAAT AAGGTTACCA CCCAAGCTAA AAGGATTTTC 120

ACTTACAATA ATGAGTTTAA GGTTACTTCT AAAGAATTGG ATCAACGCCA AAGCAATGAA 180

GTCAAAGACC TGTTTAGGAC TAACCCTGAT GTGAATGTGG GCGGAGGGAG CGTGATGGGG 240

CAGAAAATCT ACGTGAGAGG CATTGAAGAC AGGCTTTTAA GGGTTACGGT GGATGGGGCT 300

GCGCAAAATG GCAACATTTA CCACCACCAA GGCAACACCG TGATTGACCC TGGCATGCTC 360

AAAAGCGTGG AAGTTACTAA AGGCGCGGCG AATGCGAGCG CGGGGCCAGG AGCGATCGCG 420

GGAGTGATTA AAATGGAGAC TAAAGGAGCG GCTGATTTTA TCCCTAGGGG GAAAAATTAT 480

GCAGCGAGTG GGGCGGTGAG TTTTTATACC AATTTTGGGG ACAGAGAGAC TTTTAGATCG 540

GCCTATCAAA GCGCGCATTT TGATATTATC GCTTACTAG 579 (2) INFORMATION FOR SEQUENCE NO. 31:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 381 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular (ii) MOLECULA TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE : NOT

166

(vi) ORIGINAL SOURCE: Helicobacter pylori (A) ORGANISM: (Ix) SIGN: (A) TITLE / KEY: (B) LOCATION different characters 381 (Xi) SEQUENCE DESCRIPTION: Sequence # 31:

GTGCCCTTGA GTTTGGGAGG CAACCTCTTA AACCCTAACA ACAGTAGCGT GCTGAATTTA 60

AAAAACAGCC AGCTTGTTTT TAGCGATCAA GGGAGCTTGA ATATCGCTAA CATTGATTTA 120

CTAAGCGATC TGAATGGTAA TAAAAATCGT GTGTATAACA TCATTCAAGC GGACATGAAT 180

GGTAATTGGT ATGAGCGTAT CAACTTCTTTGGCATGCGCA TTAATGATGG GATTTATGAC 240

GCTAAAAACC AAACTTATAG TTTCACTAAC CCTCTCAATA ACGCCGTAAA ATTCACCGAG 300

AGCTTTTTCA TACACCGCCT GTGCGGTTCG CTCTCTCAAA TACAAAAAAA AAAAAACACA 360

ATAGTCTCAC CTCGGCTCTG A 381 (2) INFORMATION FOR SEQUENCE NO. 32:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 1698 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular (ii) MOLECULAR TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE : NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) NAME / KEY: different characters (B) LOCATION 1 ... 1698 (xi) SEQUENCE DESCRIPTION: Sequence ô. 32:

GTGTATTCTT ATAGCGATGA CGCACAAGGC 60 GTGTTTTATC TCACGAGCAG CGTGAAAGGC 60

TATTACAACC CCAACCAATC CTATCAAGCC AGCGGCAGCA ATAACACCAC GAAAAATAAC 120

AATCTAACCT CTGAATCTTC TGTCATTTCG CAAACCTATA ACGCGCAAGG CAACCCTATC 180

AGCGCGTTAC ACGTCTATAA CAAGGGCTAT AATTTCAGTA ATATCAAAGC GTTAGGGCAA 240

167

ATGGCGCTCA AACTCTACCC TGAAATCAAA AAGATATTAG GGAATGATTT TTCGCTTTCA 300 AGTTTGAGCA ATTTAAAAGG CGATGCGCTA AACCAGCTTA CCAAGCTCAT CACGCCTAGC 360 GATTGGAAAA ACATTAACGA GTTGATTGAT AACGCAAACA ATTCGGTCGT GCAAAATTTC 420 AATAACGGCA CTTTGATTAT AGGAGCGACT AAAATAGGGC AAACAGACAC CAATAGTGCG 480 GTGGTTTTTG GGGGCTTGGG CTATCAAAAG CCTTGCGATT ACACTGATAT TGTGTGCCAA 540 AAATTTAGAG GCACTTATTT GGGGCAGCTT TTGGAGTCCA ACTCCGCTGA TTTGGGCTAT 600 ATTGACACGA CTTTTAACGC TAAAGAAATT TATCTTACCG GCACTTTAGG GAGCGGGAAC 660 GCATGGGGGA CTGGGGGGAG TGCGAGCGTA ACTTTTAACA GCCAAACTTC GCTCATTCTC 720 AACCAAGCGA ATATCGTAAG CTCGCAAACC GATGGGATTT TTAGCATGCT GGGTCAAGAG 780 GGCATCAATA AGGTTTTCAA TCAAGCCGGG CTCGCTAATA TTTTGGGCGA AGTGGCAATG 840 CAATCCATTA ACAAAGCCGG GGGATTAGGG AATTTGATAG TAAATACGCT AGGGAGTGAT 900 AGCGTGATTG GGGGGTATTT AACGCCTGAG CAAAAAAATC AAACCCTAAG CCAGCTTTTG 960 GGGCAGAATA ATTTTGATAA CCTCATGAAC GATAGCGGTT TGAACACGGC GATTAAGGAT 1020 TTGATCAGAC AAAAATTAGG CTTTTGGACC GGGCTAGTGG GGGGATTAGC CGGACTGGGG 1080 GGCATTGATT TGCAAAACCC TGAAAAGCTT ATAGGCAGCA TGTCCATCAA TGATTTATTG 1140 AGTAAAAAGG GGTTGTTCAA TCAGATCACC GGCTTTATTT CCGCTAACGA TATAGGGCAA 1200 GTCATAAGCG TGATGCTGCA AGATATTGTC AAGCCGAGCG ACGCTTTAAA AAACGATGTA 1260 GCCGCTTTGG GCAAGCAAAT GATTGGCGAA TTTTTAGGCC AAGACACGCT CAATTCTTTA 1320 GAAAGCTTGC TGCAAAACCA GCAGATTAAA AGCGTTTTAG ACAAAGTCTT AGCGGCTAAA 1380 GGATTAGGGT CTATTTATGA ACAAGGTTTG GGGGATTTGA TCCCTAATCT TGGTAAAAAG 1440 GGGATTTTCG CTCCCTATGG CTTGAGTCAA GTGTGGCAAA AAGGGGATTT TAGTTTCAAC 1500 GCGCAAGGCA ATGTTTTTGT GCAAAATTCC ACTTTCTCTA ACGCTAATGG AGGCACGCTC 1560 AGTTTTAACG CAGGAAATTC GCTCATTTTT GCCGGAAACA ACCACATCGC TTTCACTAAC 1620 CATTCTGGAA CGCTCAATTT GTTGTCTAAT CAAGTTTCTA ACATTAACGT CACCATGCTT 1680 AACGCAGCAA CGGCCTAA 1698

(2) INFORMATION FOR SEQUENCE NO. 33:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 519 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular (ii) MOLECULA TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE : NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

168 (A) NAME / KEY: miscellaneous characters (B) LOCATION 1 ... 519 (xi) SEQUENCE DESCRIPTION: Sequence no. 33:

GTGTTTGGAT

TACCCTGAGC

AATCATAAAA

GCCAGACAAG

TTAAAAGATT

AAGCGCATTA

TATAGCGTTT

GCGATTTTAT

ATTAAAACTT

TGAGTTTGGC

CTTACAAGTT

TGAACGATTA

GCTTTGTCAG

TTTGTATTAA

ATGGCGAATT

TACCCGATAT

CGGTAAAAAA

TTGCAATCGC

GGATATGATT

TTTACAGGTT

TATCAAGCAA

CGTAATTGGA

AAACAATGTA

AGATAAGGTC

TATTCTTTAT

TTCGTTTAGA

CTGTAACTTC

TTAGAGCGTT

TTTTACGCGC

AATAAGAGCA

AGAGCGTTAG

AAAATGACGA

AAACGGGCTT

CAAACCAACA

GAGCGTTTCA

TCACATTAA

TTAAAGATTT

AAGAAAAAGA

AGGAAGAGGC

AAAAAATCAT

ACGATAAAAC

TATTGGTGCA

AAGATAATAT

CAAAAGACGC

TATGAGAGAA

ACGCTTCTTA

TAGTATTTTG

AGAACTTTTA

CTTAAGGGCT

TTTTGGAGGA

CAAAATCCTA

CTTATTGGAA

120

180

240

300

360

420

480

519 (2) INFORMATION FOR SEQUENCE NO. 34:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 996 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular (ii) MOLECULA TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE : NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) NAME / KEY: various characters (B) LOCATION 1 ... 996 (xi) SEQUENCE DESCRIPTION: Sequence no. 34:

ATGAAAAGAT TTGTTTTATT GCTGAGCAAG ATTACTTTTT TAGGGATTTT CTTGATAAAA AGCTCTCCCA AACAATACAG TACACTGCTA CTGGGGTTAG AGAGCCTGAT

ATATGTGTTT GCGTTTGCGT TCAAGCTTAC AAATCTATAG ATTTGCCCCA AAAACTCCAC CCATGCGCGC AACTTAACGC ATCAAAACAC GCCTGCACCA AGAGTTTTAA AAAATCCGCT TTAGTGAGCC AAACACAÄACC

120

180

240

300

360

169

AGCGAGGACA ATATCAATTT TTACATGCCT TATATGAACA TGGCTTATTG GTTTGTCAAA 420 AAAGAATTTC CTAGCCCAGA ATATGAAGAT TTCATTAGGC GGATGCGTCA GTATTCTCAA 480 TCAGCTCTTA ACACTAACCA TGGGGCGTGG GGGATTCTCT TTGATGTGAG CTCTGCACTA 540 GCGCTAGATG ATCATGCCCT TTTGCAAAGT AGCGCTAATC GGTGGCAGGA GTGGGTGTTT 600 AAAGCCATAG ATGAGAACGG GGTTATTGCT AGCGCGATCA CTAGGAGCGA TACGAGCGAT 660 TATCATGGCG GCCCTACAAA GGGCATTAAG GGGATAGCTT ATACCAATTT TGCGCTTCTT 720 GCGATAACTA TATCAGGCGA ATTGCTTTTT GAGAACGGGT ATGATTTGTG GGGTAGTGGA 780 GCCGGGCAAA GGCTCTCTGT GGCGTATAAC AAAGCCGCAA CATGGATTCT AAACCCTGAA 840 ACTTTCCCCT ATTTTCAGCC TAACCTCATT GGGGTGCATA ACAACGCCTA TTTCATTATT 900 TTAGCCAAAC ATTATTCTAG CCCTAGCGCG GATGAGCTTT TAGAGCAAGG CGATTTGCAT 960 GAAGATGGCT TCAGGCTGAA ACTCCGATCG CCATGA 996 (2) INFORMATION FOR SEQ ID NO. 35:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 384 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular (ii) MOLECULAR TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE : NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) TITLE / KEY: various characters (B) LOCATION 1 ... 384 (xi, SEQUENCE DESCRIPTION: Sequence No. 35:

ATGCGTCAGT ATTCTCAATC AGCTCTTAAC ACTAACCATG GGGCGTGGGG GATTCTCTTT 60

GATGTGAGCT CTGCACTAGC GCTAGATGAT CATGCCCTTT TGCAAAGTAG CGCTAATCGG 120

TGGCAGGAGT GGGTGTTTAA AGCCATAGAT GAGAACGGGG TTATTGCTAG CGCGATCACT 180

AGGAGCGATA CGAGCGATTA TCATGGCGGC CCTACAAAGG GCATTAAGGG GATAGCTTAT 240

ACCAATTTTG CGCTTCTTGC GATAACTATA TCAGGCGAAT TGCTTTTTGA GAACGGGTAT 300

GATTTGTGGG GTAGTGGAGC CGGGCAAAGG CTCTCTGTGG CGTATAACAA AGCCGCAACA 360 TGGATTCTAA ACCCTGAAAC TTTC 384 (2) INFORMATION FOR SEQUENCE NO. 36:

170 (i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 738 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular (ii) MOLECULA TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE : NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) NAME / KEY: various characters (B) LOCATION 1 ... 738 (xi) SEQUENCE DESCRIPTION: Seq. 36:

TTGAGAACCT TGTTAAAAAT GTTGGTTGGT GTGAGCTTAC TAACACACGC TTTAATGGCT 60

ACAGAAGAAA GCGCTGCCCC TTCTTGGACA AAAAATTTGT ATATGGGATT CAATTACCAA 120

ACAGGTTCTA TCAATTTAAT GACTAATATT CATGAAGTTA GAGAAGTTAC TAGCTATCAA 180

ACCGGTTACA CCAATGTAAT GACTAGCATT AATAGCGTTA AAAAACTCAC TAACATGGGT 240

TCTAATGGGA TTGGCTTAGT CATGGGCTAT AACCACTTTT TCCATCCGGA TAAAGTCTTG 300

GGTTTGCGCT ATTTTGCTTT TTTAGATTGG CAAGGCTATG GCATGAGATA CCCTAAAGGC 360

TATTATGGGG GCAATAACAT GATCACTTAT GGCGTGGGCG TGGATGCGAT ATGGAATTTC 420

TTCCAAGGGA GTTTTTATCA AGATGATATT GGCGTGGATA TTGGCGTTTT TGGGGGGATT 480

GCGATTGCTG GGAATAGCTG GTATATTGGC AATAAAGGGC AGGAATTATT AGGCATCACC 540

AATAGTAGTG CGGTTGATAA CACCTCTTTT CAATTCCTCT TTAACTTTGG TTTCAAAGCT 600

TTATTTGTAG ATGAACATGA ATTTGÄAATT GGGTTTAAAT TCCCCACTCT TAACAACAAA 660

TACTACACCA CCGACGCGCT CAAGGTTCAA ATGCGTAGGG TCTTTGCCTT TTATGTGGGG 720 TATAATTACC ACTTCTAA 738 (2) INFORMATION FOR SEQUENCE NO. 37:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 873 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular

171 (ii) MOLECULA TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) NAME / KEY: various characters (B) LOCATION 1 ... 873 (xi) SEQUENCE DESCRIPTION: Sequence £. 37:

ATGTTTGAAG AAATTACCCT AGCGCATAAG GACTTGTTTT CAAGGTTTTT ACAAACTCAA 60

AAAATCGTTT TATCGGATGT GAGTTTTACC AATTGCTTTT TATGGCAGCA CGCAAGGCTC 120

ATTCAAGTGG CTGTGATTAG GGATTGTTTG GTGATTCAAA CCACTTATGA AAACCAAAAA 180

CCCTTTTATT TCTATCCTAT CGGTAAGAGG CCGCATGAAT GCGTGAAAGA GCTTTTGGAA 240

TTAGAAAAAA ATTTAAGATT CCACTCCCTG ACTTTAGAGC AAAAAGACGA TTTGAAAGAC 300

AATTTTGTAG GGGTGTTTGA TTTCACTTAC AACCGAGACA GGAGCGATTA TGTTTATTCT 360

ATTGAAGAAC TAATCGCGCT CAAAGGGAAA AAATACCATA AGAAAAAAAA CCACTTAAAC 420

CAGTTTTTAA CCAATCATGC GAATTTTGTT TATGAAAAAA TTTCTCCTCA AAACAGAAAG 480

GAAGTTTTAG AAGCCTCTAA AGCGTGGTTT TTAGAAAGCC AGACCGATGA TATAGGGTTA 540

ATCAACGÄA ATAAGGGCAT TCAAAGCGTT TTAGAAAATT ATGAAAGCTT GGATTTAAAG 600

GGGGGGCTTA TTAGGGTTAA TGGGGAAATA GTCTCGTTTA GTTTTGGGGA AGTTTTAAAC 660

GAAGAGAGCG CGCTCATCCA CATTGAAAAA GCCCGCACAG ATATTGCAGG CGCGTATCAA 720

ATCATCAACC AACAATTGCT TTTGAATGAA TTTAGCCATT TAACTTACGC TAACAGAGAA 780

GAAGATCTAG GATTAGAGGG CTTAAGAAGG TCTAAAATGA GCTATAACCC GGTGTTTTTG 840

ATAGACAAAT ACGAAGCGGT TGCTAGAAAT TAA 873 (2) INFORMATION FOR SEQUENCE NO. 38:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 333 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular (ii) MOLECULAR TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE : NOT

(Vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (Ix) SIGN: (A) TITLE / KEY: (B) LOCATION different characters 1 ... 333 (Xi) SEQUENCE DESCRIPTION: Sequence # 38:

ATGATGTTCA TTGTAGCGGT 60TGATGCTG GCGTTTTTGA TCTTTGTCCA TGAGTTAGGG 60

CATTTCATTA TCGCTAGGAT TTGTGGGGTG AAAGTGGAAG TGTTTAGCAT TGGTTTTGGT 120

AAAAAACTCT GGTTTTTCAA GCTTTTTGGC ACGCAATTCG CTCTGTCTTT GATCCCGCTT 180

GGGGGCTATG TGAAATTAAA GGGCATGGAT AAAGAAGAAA ATGAAGAAAA ΤΑΑΑΑΤΤΑΑΤ 240

CAAGCGAATG ATAGCTACGC CAAAAAAGCC CTTTCCAAAA GCTATGGATA TTGTTTGGTG 300

GGGCGTTTTT TAATTTTCTT TTTGCGGTTT TAG 333 (2) INFORMATION FOR SEQUENCE NO. 39:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 1056 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular (ii) MOLECULA TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE : NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) NAME / KEY: various characters (B) LOCATION 1 ... 1056 (xi) SEQUENCE DESCRIPTION: Sequence no. 39:

ATGATGTTCA TTGTAGCGGT 60TGATGCTG GCGTTTTTGA TCTTTGTCCA TGAGTTAGGG 60

CATTTCATTA TCGCTAGGAT TTGTGGGGTG AAAGTGGAAG TGTTTAGCAT TGGTTTTGGT 120

AAAAAACTCT GGTTTTTCAA GCTTTTTGGC ACGCAATTCG CTCTGTCTTT GATCCCGCTT 180

GGGGGCTATG TGAAATTAAA GGGCATGGAT AAAGAAGAAA ATGAAGAAAA ΤΑΑΑΑΤΤΑΑΤ 240

173

CAAGCGAATG ATAGCTACGC GCAAAAAAGC CCTTTCCAAA AGCTATGGAT ATTGTTTGGT 300 GGGGCGTTTT TTAATTTTCT TTTTGCGGTT TTAGTGTATT TTTTTCTGGC ATTGAGCGGG 360 GAAAAAGTCT TACTGCCCGT CATTGGCGGT TTAGAAAAAA ACGCGCTAGA AGCCGGGCTG 420 TTAAAGGGGG ATAGAATCCT TTCTATCAAC CATCAAAAAA TAGCGAGTTT TAGAGAGATT 480 AGAGAGATAG TGGCGCGTTC TCAAGGCGAG TTAATTTTAG AAATAGAGCG AAACAATCAG 540 ATTTTAGAAA AACGACTGAC CCCCAAAATC GTGGCGGTGA TAAGCGAGTC TAATGATCCT 600 AATGAAATCA TCAAGTATAA AATAATAGGC ATTAAACCGG ACATGCAAAA AATGGGCGTT 660 GTCTCTTATT CCGTGTTTCA AGCGTTTGAA AAGGCTTTGA GTCGGTTTAA AGAGGGCGTT 720 GTTTTGATTG TGGATTCTTT AAGGCGTTTG ATTATGGGGA GCGCTTCAGT TAAAGAATTG 780 AGTGGGGTAA TAGGCATTGT GGGGGCGTTA AGCCATGCCA ATAGCGTGAG CATGCTTTTG 840 TTGTTTGGGG CGTTTTTATC TATCAATCTA GGGATTTTAA ATTTATTACC CATTCCAGCC 900 TTAGATGGGG CGCAAATGCT AGGGGTCGTT TTTAAAAATA TTTTTCATAT CGCTTTGCCA 960 ACGCCCATAC AAAATGCGTT GTGGCTAGTG GGGGTGGGGT TTTTGGTTTT TGTCATGTTT 1020 TTAGGGCTTT TTAATGACAT TACTCGTTTG CTATAA 1056

(2) INFORMATION FOR SEQUENCE NO. 40:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 303 base pairs (B) TYPE: nucleic acid (C) NUMBER OF FIBERS: two (D) TOPOLOGY: circular (ii) MOLECULAR TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE : NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (Ix) SIGN: (A) NAME / KEY: different characters (B) PLACEMENT 1 ... 303 (Xi) DESCRIPTION i SEQUENCES: Sequence £. 40:

ATGCAAAAGA ATTTGGATAG TCTTTTAGAA AATTTAAGGG CTGAAATTGA TGCGTTGGAT 60 AATGAATTGA GCGATCTTTT AGACAAACGC TTAGGAATCG CTTTAAAAAT CGCTCTCATC 120 AAACAAGAAA GCCCCCAAGA AAACCCCATT TATTGCCCTA AAAGAGAGCA AGAGATTTTA 180 AAACGACTCA GCCAAAGGGG TTTCAAGCAT TTGAATGGAG AAATCCTTGC AAGTTTTTAT 240 GCAGAGGTTT TTAAGATTTC TAGAAATTTT CAAGAAAACG CCCTAAAAGA GTTAAAAAAA 300 TAA 303

174 (2) INFORMATION FOR SEQUENCE NO. 41:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 525 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular (ii) MOLECULAR TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE : NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) NAME / KEY: various characters (B) LOCATION 1 ... 525 (xi) SEQUENCE DESCRIPTION: Sequence no. 41:

GTGAAAATGC GTTTTTTTAG TGGTTTTGGG TTTGTTAATG AAAGCGTTTT GTTTGAAGAG TGGCTTTTAA AAGGGGCTTA TGATGTGTCA GGCTTTTCTA TGGGGGCGAT TAAGGCGATA GAATACGCCT ATAATGAAGT CTTGCAACAA CGGCGCATCC ATTCCTTATT GTTGTTTTCG CCTTGCATGC TAGCGCATAA GAGTTTGGCG TTCAAACGCT TGCAACTTTT CTTGTTTCAA AAAGATCCGC AAAGCTACAT GGATAACTTT TATAAGGAAG TGGGATTGGA CGCTCAATTG GAGCGTTTTA AAAAAGAGGG TTCTTTAGAA GAATTGGAAT TTTTATTGGA TTACAAGTAT AGTGATTCTA TAATTAGATT TTTATTGGAA AAGGGCGTGA AGATTGAAGT GTTTATCGGT TTAAAAGATA GAATCACTGA CATTCAAGCC CTTTTAGAAT TTTTTATGCC CTTAGTTCAA GTGTGGCAGT TTAAGGATTG TAACCATTTG TTGCAAAAAT CTTAA (2) INFORMATION FOR SEQUENCE NO. 42:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 1416 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular

120

180

240

300

360

420

480

525 (ii) MOLECULA TYPE: DNA (genomic)

175

(Iii) HYPOTHETICAL: NO (Iv) ANTI-SENSE: NO (Vi) ORIGINAL SOURCE: (A) ORGANISM: Helicobacter pylori (Ix) SIGN: (A) TITLE / KEY: (B) LOCATION different characters 1 ... 1417 (Xi) SEQUENCE DESCRIPTION: Sequence £. 42:

ATGAAAAATA CCAATACAAA AGAGATAAAG AATACAAGGA TGAAAAAAGG TTATAGTCAA 60 TACCACACGC TCAAAAAAGG GCTTTTAAAA ACCGCTCTGC TTTTTAGCCT TCCTTTAAGC 120 GTGGCGTTAG CTGAAGACGA TGGCTTTTAT ATGGGAGTGG GCTATCAAAT CGGCGGCGCG 180 CAACAAAACA TCAACAACAA AGGCAGCACC CTAAGGAATA ATGTCATTGA TGATTTCCGC 240 CAAGTGGGCG TGGGTATGGC AGGGGGTAAT GGGCTTTTAG CTTTAGCGAC AAACACGACC 300 ATGGACGCTC TTTTAGGGAT AGGCAACCAA ATTGTCAATA CTAATACAAC TGTTGGCAAC 360 AACAACGCAG AGTTAACCCA GTTTAAAAAA ATACTCCCCC AAATTGAACA ACGCTTTGAG 420 ACGAATAAAA ACGCTTATAG CGTTCAAGCC TTGCAAGTGT ATTTGAGTAA TGTGCTTTAT 480 AACTTGGTTA ATAATAGTAA TAATGGTAGC AATAATGGAG TCGTTCCTGA ATATGTAGGG 540 ATTATAAAAG TTCTCTATGG TTCTCAAAAT GAATTCAGTC TCTTAGCCAC GGAGAGTGTG 600 GCGCTTTTAA ACGCGCTCAC GAGAGTGAAT CTGGATAGTA ATTCGGTGTT TTTAAAAGGG 660 CTATTAGCCC AAATGCAGCT TTTTAATGAC ACTTCTTCAG CAAAGCTAGG TCAGATCGCA 720 GAAAACTTGA AGAACGGTGG TGCAGGGGCC ATGCTTCAAA AGGATGTGAA AACCATCTCG 780 GATCGAATCG CTACTTACCA AGAGAATCTA AAACAGCTAG GAGGGATGTT AAAGAATTAC 840 GATGAGCCAT ACCTACCCCA ATTTGGGCCA GGCACAAGCT CTCAGCATGG GGTTATTAAT 900 GGCTTTGGCA TTCAAGTGGG CTATAAGCAA TTTTTTGGGA GCAAGAAGAA TATAGGCTTA 960 CGATATTACG CTTTCTTTGA TTATGGCTTT ACGCAATTGG GCAGTCTTAA CAGTGCTGTT 1020 AAAGCGAACA TCTTTACTTA TGGTGCTGGC ACGGACTTTT TATGGAATAT CTTTAGAAGG 1080 GTTTTTAGCG ATCAGTCCTT GAATGTGGGG GTGTTTGGGG GCATTCAAAT AGCGGGTAAC 1140 ACTTGGGATA GCTCTTTAAG AGGTCAAATT GAAAACTCGT TTAAAGAATA CCCCACTCCC 1200 ACGAATTTCC AATTTTTGTT TAATTTGGGC TTAAGGGCTC ATTTTGCCAG CACCATGCAC 1260 CGCCGGTTTT TGAGCGCGTC TCAAAGCATT CAGCATGGTA TGGAATTTGG CGTGAAAATC 1320 CCAGCTATCA ATCAAAGGTA TTTGAAAGCG AATGGGGCTG ATGTGGATTA CAGGCGTTTG 1380 TATGCGTTCT ATATCAATTA CACGATAGGT TTTTAA 1416

(2) INFORMATION FOR SEQUENCE NO. 43:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 390 base pairs (B) TYPE: nucleic acid (C) FIBERS: two

176 (D) TOPOLOGY: circular (ii) MOLECULA TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) NAME / KEY: various characters (B) LOCATION 1 ... 390 (xi) SEQUENCE DESCRIPTION: Sequence no. 43:

ATGAAAAGCA TCAGAAGAGG CGATGGGCTG AATGTTGTCC CTTTCATTGA TATTATGCTC GTCTTACTAG CGATTGTGTT GAGTATTTCT ACTTTTATCG CGCAAGGTAA GATTAAAGTC AGTCTCCCTA ACGCTAAAAA TGCGGAAAAA TCCCAGCCAA ACGATCAAAA AGTGGTGGTC ATCTCTGTGG ATGAGCATGA CAATATTTTC GTAGATGACA AACCGACGAA TTTAGAAGCT TTGAGCGCTG TAGTCAAGCA AACAGACCCT AAAACCCTTA TAGATTTAAA AAGCGACAAG AGCTCTCGTT TTGAAACTTT TATCAGCATT ATGGATATTT TAAAAGAGCA TAATCATGAA AATTTCTCCA TCTCCACGCA AGCTCAGTAA

120

180

240

300

360

390 (2) INFORMATION FOR SEQUENCE NO. 44:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 225 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular (ii) MOLECULAR TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE : NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) TITLE / KEY: different characters

177 (B) LOCATION 1 ... 225 (xi) SEQUENCE DESCRIPTION: Sequence £. 44:

ATGCTCGTCT TACTAGCGAT TGTGTTGAGT ATTTCTACTT TTATCGCGCA AGGTAAGATT 60 AAAGTCAGTC TCCCTAACGC TAAAAATGCG GAAAAATCCC GACCAAACGA TCAAAAAGTG 120 GTGGTCATCT CTGTGGATGA GCATGACAAT ATTTTCGTAG ATGACAAACC GACGAATTTA 180 GAAGCTTTGA GCGCTGTAGT CAAGCAAACA GACCCTAAAA CCCT 225 (2) INFORMATION FOR SEQ ID NO. 45:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 672 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular (ii) MOLECULA TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE : NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) NAME / KEY: various characters (B) LOCATION 1 ... 672 (xi) SEQUENCE DESCRIPTION: Sequence no. 45:

ATGTTTTCAC TTTCTTATGT TTCCAAGAAA TTTTTAAGCG TGTTGCTATT GATTTCGCTG 60 TTTTTAAGCG CTTGCAAATC CAACAATAAA GACAAATTGG ATGAAAATCT TTTAAGCTCC 120 GGCACTCAAA GCTCCAAAGA ATTAAACGAC AAGCGAGACA ATATAGACAA AAAGAGCTAC 180 GCTGGTTTAG AAGATGTTTT TTTAGACAAC AAGTCCATTA GCCCTAATGA TAAATACATG 240 CTTTTAGTTT TTGGCCGTAA TGGTTGCTCC TATTGTGAAA GGCTTAAAAA AGATCTCAAA 300 AATGTCAAAG AATTGCGCAA CTATATTAAA GAGCATTTTA GTGCTTACTA TGTCAATATC 360

AGCTATTCTA AAGAGCATAA TTTTAAAGTC GGCGATAAGG ATAAAAATGA TGAAAAAGAA 420 ATCAAAATGT CCACAGAAGA ATTAGCGCAA ATTTATGCCG TCCAATCCAC CCCTACGATT 480 GTTTTATCCG ATAAAACCGG CAAAACCATC TATGAATTGC CGGGCTATAT GCCTTCTGTG 540 CAATTTTTAG CCGTGTTAGA ATTTATCGGC GATGGGAAGT ATCAAGACAC GAAAAACGAT 600 GAGGATCTCA CTAAAAAATT AAAGGCTTAC ATCAAGTATA AAACCAACCT TTCTAAGAGC AAGTCCAGCT 660 AG 672

178 (2) INFORMATION FOR SEQUENCE NO. 46:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 351 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular (ii) MOLECULAR TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE : NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) NAME / KEY: various characters (B) LOCATION 1 ... 351 (xi) SEQUENCE DESCRIPTION: Sequence no. 46:

TTGATGAAAT CTAAAATCAC TCATTTTATC GCCTGCAAAG ATGAGCCTAA AAAATCGTCC CAAAACAATC AAATCAATCA ACCTAATAAG GATGAAAAAG TCACCAAAGA AGTGAATGAT ATCAATAATG AAGAAAACGC TGACCCTTCG

GTTATCTCTT TTGTTTTAAG CGTGTTGAGC CAATCGCACC AAAACAACAC TAAAACCACT GATATAAAAA AGATTGAGCA TGAAGAAGAA CTGATCAATA ACGAAAATAA AATTGATGAA CAAAAAAGAA CGAACAATGT TTTGCA

120

180

240

300

351 (2) INFORMATION FOR SEQUENCE NO. 47:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 240 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular (ii) MOLECULAR TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE : NOT

179 (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) NAME / KEY: various characters (B) LOCATION 1 ... 240 (xi) SEQUENCE DESCRIPTION: Sequence no. 47:

ATGTTTGAAA AAATACGCAA GATTTTAGCG ATATGCAAAA TGAAATTGAA 60

ATGCTTTTAA AATTAGCGAA TTTGAGTTTG GGGGATTTTA TTGAGATTAA AAGAGGGAGC 120

ATGGACATGC CAAAGGGCGT GAATGAAGCG TTTTTTACGC AATTAAGCGA AGAAGTGGAG 180

CGCCTAAAGG AGCTTATCAA CGCTTTGAAT AAAATCAAAA AAGGGTTATT GGTGTTTTAA 240 (2) INFORMATION FOR SEQUENCE NO. 48:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 156 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular (ii) MOLECULA TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE : NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) TITLE / KEY: various characters (B) LOCATION 1 ... 156 (xi) SEQUENCE DESCRIPTION: Sequence no. 48:

ATGTCTATGT TCATTTCTAA TCTGGCTTTC ACGAGCGAAC ATAAGGACGC TATGGAAGTG 60 GCAAAAATTG CGATTTTACT CGGATCTTTG ATTTCTGGGA TCATAGGGGC TTTATATTTA 120 49

180 (i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 1350 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular (ii) MOLECULA TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE : NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) NAME / KEY: various characters (B) LOCATION 1 ... 1350 (xi) SEQUENCE DESCRIPTION: Sequence no. 49:

ATGGGTTTGA AAATAAAAAT CTCAGTTTGA CGCTTAAAAA TTGAACGCCG TTTTAGCGAT CTATGGCACA CCCCTTTTGG AACTGGATTG ATGATGTCTT CGAGAATTGT TGTTTGGGGA GCCATAGGGG GCATGATAGC TCTCAGCATG GTTTTGGGAT ATGCTTTTAG GCAAGAGGGT GCTGATGACT TAGGGGCTAT GCATGGCTTT TAGGGGCTTT ATCCGATCGC TCATCCCTTA AGCGGTATCC ATGCGACGAT CCTAAAGATT CTAAAAATGT TCAGGAGTGC TTTTAACCAA AGTGCTTTAC AAAGCCCCTT TTCATCATGC CCTTATTCGC TTAGAAGTGG ATAAGGTGCT GGGATTTTCT TAATCACTTT ATCGGCTGGT GGCATATTTT ATGTTCATTT CTAATCTGGC ATTGCGATTT TACTCGGATC CTAGATAAAA GAGCGGCTTT

TTTAAGGTTG TCTATGAATC CTTCATTAAA AGCGAGTCTT GGTGGTGGCT AATTCGTTTT GTTTCAAGTA GGGGATTTTT AATGGCGTTA TTCTTTTTAA ATTATCCAGT TTTAAAAAAG TCCAGGATTG ATTTATTTTT CCCTATGGCA ACGGATATTG GCCAACCGCC TTAAAGGTTT TGTGGTGATC GCGCTCTTTT AGGGGTGGTT CTTGTTTTAG CTTGCTTTTA GGGGTGTTGC CGCTGCGGTG GTTCTAGCTT AGAGCTTTTG GAATTAGGCA AGAGCAGCAA GAAATCTTGC AGAAAGATTG GAGCATTTTC GTTTGCAAAC GCTGGGGTGA TTTAGGGGTT ATTTTAGGGC CATAAGCGAA AAGCTTAAAA AGGGGCTGGG CTTTTAGCAG TTTCACGAGC GAACATAAGG TTTGATTTCT GGGATCATAG AAAGAAATAG

TCAAAAAAAC AGAAAACGCG TTGGAGGGAT TTTCCTCTTT TAAAAGAAAG TTATTTTGCG TTATCGGCTT TAGTTTGCAC TGATAGGCTT AGAGATCAAG CTTCTTTCCC TGTGATCGCA TTCTTAACGC CAACACGCCC CGTTCGCTTT AGGCGTGATC TTTTAATCAC TCTAGCGGTG ATACCACGAA TTTAAAATTC CCATATTGAA CCGCCTGAAT TTTGGTTTTG CGTGCATCAA TTATGATACC GGTGAAAATC AACGATACGC AGAGACGAGT ATTCTATTGA AGAAAAAGCG TAGCCCCCAT CAGCGGGTAT GCGTTGATTC TAGCATCAAT TTTGTTTGGG CAAGCCTTTA TCACTGCGCG CCCTAAAGGC GGATTGGCTT TACCATGTCT ACGCTATGGA AGTGGCAAAA GGGCTTTATA TTTATTCGCA

120

ISO

240

300

360

420

480

540

600

660

720

780

840

900

960

1020

1080

1140

1200

1260

1320

1350

181 (2) INFORMATION FOR SEQUENCE NO. 50:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 2448 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular (ii) MOLECULAR TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE : NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) NAME / KEY: various characters (B) LOCATION 1 ... 2448 (xi) SEQUENCE DESCRIPTION: Sequence £. 50:

ATGAATGACA AGCGTTTTAG AAAATATTGT AGTTTTTCTA TTTTTTTGTC CTTATTAGGA 60 ACGTTTGAAT TAGAGGCTAA AGAAGAAGAA AAAGAAGAAA AAAAGACAGA AAGGAACAAA 120 GATAAAGAAA AGAACGCCCA ACACACTTTG GGTAAAGTTA CCACTCAAGC GGCTAAAATC 180 TTTAATTACA ACAACCAGAC AACCATTTCA AGTAAAGAAT TAGAAAGAAG GCAAGCCAAC 240 CAAATCAGCG ACATGTTTAG AAGAAACCCC AATATCAATG TGGGCGGTGG TGCGGTGATA 300 GCGCAAAAAA TTTACGTGCG CGGTATTGAA GACAGATTGG CTAGGGTTAC GGTGGATGGC 360 GTGGCGCAAA TGGGCGCAAG CTATGGGCAT CAAGGCAATA CAATCATTGA CCCTGGAATG 420 CTCAAAAGCG TGGTGGTTAC CAAGGGGGCG GCTCAAGCGA GCGCGGGGCC TATGGCTTTA 480 ATTGGCGCGA TCAAAATGGA GACTAGGAGC GCGAGCGATT TTATCCCTAA AGGCAAAGAC 540 TACGCCATAA GTGGGGCTGC CACTTTTTTA ACCAACTTTG GGGATAGGGA AACCATTATG 600 GGCGCTTATC GTAACCATCA TTTTGATGCG CTTTTGTATT ACACGCACCA AAATATTTTT 660 TATTATCGTG ATGGGGATAA CGCGATGAAA AATCTTTTTG ACCCTAAAGC GGATAATAAA 720 GTTACAGCAA GCCCTAGCGA ACAAAACAAT GTGATGGCTA AGATCAATGG TTATTTGAGC 780 GAAAGGGATA CCTTAACGCT CAGTTATAAC ATGACTAGAG ATAACGCCAA TCGCCCTTTA 840 AGAGCGAATT TTACCGGCAC TTTTTTACCC TATTCTTGTG GTGATTTCAA CGCTTTCCCT 900 AACGAGAAAA ACCCTAGCGA TTGTTTGTTT GAAAATGACG CCAGTTTGTT TAAAACTTAT 960 AGCGTCAATT TAGTGCATAA CGTGAGCTTG AATTATGAAA GGGAAGGGGG GAGTCGCTTT 1020 GGCGATCCTA AATTAAAAAT CAATGGCTAC ACGAGCATTA GGAATGTCCA AATTGATCCG 1080 CTTTTCAGAC CTAGCGATAT AGCGACTACC ATTCCTTTCA CCCCAAACCC GCAGCTCTCT 1140 CAAGGCGAAG AAAATCAATG CGTGGCGCAA GGGGGCATTT ATGACGCTCT TAAACAAACT 1200

182

TGCTCCATCA CTTTTAAAAG CCTTGGAGGG GGTTCTGTTG TCGCTAATAA AAATTTATTC ATCATCAATT CTGGGTTTAA TGCGAACGTG ATCCACACCA TAGACCACAA GAATGACAAT CTTTTGGAAT ACGGGTTGAA TTACCAGAAT TTAACCACTT TTGATAAAGC GATCCCTGAT AGCGAATTAG TCAAGCCCGG CGATGCCCCT GATGCGTGCT TAAGAGTTAC AGGACCTGAT GATCCTAACA TGAACGGGCG CTGCCAACGG AATGGCGCTA CGGCGAATGT GGTTGGGGTG TATGCGCAAG CGAATTACAC CTTGCACCCT ATGGTAACTT TAGGGGCAGG GACTCGTTAT GACGTTTATA CTTTAGTGGA TAAAGACTGG CAATTGCACG TAACTCAAGG GTTTAGCCCT AGCGCGGCTT TAAACGTCTC GCCTTTAGAA AATTTGAATT TCAGGCTTTC TTACGCGTAT GTAACTAGAG GCCCTATGCC TGGAGGTTTG GTGTGGATGC GTCAAGACAA TTTGCGCTAT AACCGCAATT TAAAGCCAGA AATTGGGCAA AATGCGGAAT TTAACACCGA ATACAGCAGT CAGTATTTTG ATTTCAGAGC CGCCGGTTTT GTCCAATTGA TTTCTAATTA CATCAATCAA TTTTCTTCAA CGCTTTTTGT CACCAACTTG CCCGCACAAG ATATTATTTA TGTGCCTGGC TATGAAGTTT CAGGGACGGC TAAATACAAG GGTTTTTCTT TAGGCTTGAG CGTGGCGCGA TCATGGCCTT CTTTAAAAGG GCGTTTGATC GCTGACGTGT ATGAATTGGC GGCTACGACA GGCAATGTGT TTATTTTAAC GGCAAGCTAT ACAATCCCAC GCACCGGCCT TAGCATCACT TGGCTTTCAC GCTTTGTTAC TAATTTGAGT TATTGCTCTT ATAGCCCTTA TCGTAACGGC CCTACGGATA TTGACAGAAG GCCTAGTAAT TGCCCTAAAA CGCCCGGGAT TTTTCATGTG CATAAACCCG GCTATGGGGT GAGCAGTTTC TTTATCACTT ACAAGCCTAC TTATAAGAAA CTCAAAGGGT TGAGCCTGAA CGCGGTGTTT AATAATGTTT TTAACCAACA ATATATTGAT CAAGCAAGCC CGGTGATGAG CCCTGATGAA CCCAATCAAG ACAAATACGC AAGGGGCATG GCAGAGCCTG GCTTTAACGC TAGGTTTGAA ATTTCTTATA AGTTTTAA (2) INFORMATION FOR SEQ ID NO. 51:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 2445 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular (ii) MOLECULA TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE : NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) NAME / KEY: various characters (B) LOCATION 1 ... 2445 (xi) SEQUENCE DESCRIPTION: Sequence no. 51:

1260

1320

1380

1440

1500

1560

1620

1680

1740

1800

1860

1920

1980

2040

2100

2160

2220

2280

2340

2400

2448

183

ATGACAAGCG TTTTAGAAAA ATATTGTAGT TTTTCTATTT TTTTGTCCTT ATTAGGAACG 60 TTTGAATTAG AGGCTAAAGA AGAAGAAAAA GAAGAAAAAA AGACAGAAAG GAACAAAGAT 120 AAAGAAAAGA ACGCCCAACA CACTTTGGGT AAAGTTACCA CTCAAGCGGC TAAAATCTTT 180 AATTACAACA ACCAGACAAC CATTTCAAGT AAAGAATTAG AAAGAAGGCA AGCCAACCAA 240 ATCAGCGACA TGTTTAGAAG AAACCCCAAT ATCAATGTGG GCGGTGGTGC GGTGATAGCG 300 CAAAAAATTT ACGTGCGCGG TATTGAAGAC AGATTGGCTA GGGTTACGGT GGATGGCGTG 360 GCGCAAATGG GCGCAAGCTA TGGGCATCAA GGCAATACAA TCATTGACCC TGGAATGCTC 420 AAAAGCGTGG TGGTTACCAA GGGGGCGGCT CAAGCGAGCG CGGGGCCTAT GGCTTTAATT 480 GGCGCGATCA AAATGGAGAC TAGGAGCGCG AGCGATTTTA TCCCTAAAGG CAAAGACTAC 540 GCCATAAGTG GGGCTGCCAC TTTTTTAACC AACTTTGGGG ATAGGGAAAC CATTATGGGC 600 GCTTATCGTA ACCATCATTT TGATGCGCTT TTGTATTACA CGCACCAAAA TATTTTTTAT 660 TATCGTGATG GGGATAACGC GATGAAAAAT CTTTTTGACC CTAAAGCGGA TAATAAAGTT 720 ACAGCAAGCC CTAGCGAACA AAACAATGTG ATGGCTAAGA TCAATGGTTA TTTGAGCGAA 780 AGGGATACCT TAACGCTCAG TTATAACATG ACTAGAGATA ACGCCAATCG CCCTTTAAGA 840 GCGAATTTTA CCGGCACTTT TTTACCCTAT TCTTGTGGTG ATTTCAACGC TTTCCCTAAC 900 GAGAAAAACC CTAGCGATTG TTTGTTTGAA AATGACGCCA GTTTGTTTAA AACTTATAGC 960 GTCAATTTAG TGCATAACGT GAGCTTGAAT TATGAAAGGG AAGGGGGGAG TCGCTTTGGC 1020 GATCCTAAAT TAAAAATCAA TGGCTACACG AGCATTAGGA ATGTCCAAAT TGATCCGCTT 1080 TTCAGACCTA GCGATATAGC GACTACCATT CCTTTCACCC CAÄACCCGCA GCTCTCTCAA 1140 GGCGAAGAAA ATCAATGCGT GGCGCAAGGG GGCATTTATG ACGCTCTTAA ACAAACTTGC 1200 TCCATCACTT TTAAAAGCCT TGGAGGGGGT TCTGTTGTCG CTAATAAAAA TTTATTCATC 1260 ATCAATTCTG GGTTTAATGC GAACGTGATC CACACCATAG ACCACAAGAA TGACAATCTT 1320 TTGGAATACG GGTTGAATTA CCAGAATTTA ACCACTTTTG ATAAAGCGAT CCCTGATAGC 1380 GAATTAGTCA AGCCCGGCGA TGCCCCTGAT GCGTGCTTAA GAGTTACAGG ACCTGATGAT 1440 CCTAACATGA ACGGGCGCTG CCAACGGAAT GGCGCTACGG CGÄATGTGGT TGGGGTGTAT 1500 GCGCAAGCGA ATTACACCTT GCACCCTATG GTAACTTTAG GGGCAGGGAC TCGTTATGAC 1560 GTTTATACTT TAGTGGATAA AGACTGGCAA TTGCACGTAA CTCAAGGGTT TAGCCCTAGC 1620 GCGGCTTTAA ACGTCTCGCC TTTAGAAAAT TTGAATTTCA GGCTTTCTTA CGCGTATGTA 1680 ACTAGAGGCC CTATGCCTGG AGGTTTGGTG TGGATGCGTC AAGACAATTT GCGCTATAAC 1740 CGCAATTTAA AGCCAGAAAT TGGGCAAAAT GCGGAATTTA ACACCGAATA CAGCAGTCAG 1800 TATTTTGATT TCAGAGCCGC CGGTTTTGTC CAATTGATTT CTAATTACAT CAATCAATTT 1860 TCTTCAACGC TTTTTGTCAC CAACTTGCCC GCACAAGATA TTATTTATGT GCCTGGCTAT 1920 GAAGTTTCAG GGACGGCTAA ATACAAGGGT TTTTCTTTAG GCTTGAGCGT GGCGCGATCA 1980 TGGCCTTCTT TAAAAGGGCG TTTGATCGCT GACGTGTATG AATTGGCGGC TACGACAGGC 2040 AATGTGTTTA TTTTAACGGC AAGCTATACA ATCCCACGCA CCGGCCTTAG CATCACTTGG 2100 CTTTCACGCT TTGTTACTAA TTTGAGTTAT TGCTCTTATA GCCCTTATCG TAACGGCCCT 2160 ACGGATATTG ACAGAAGGCC TAGTAATTGC CCTAÄAACGC CCGGGATTTT TCATGTGCAT 2220 AAACCCGGCT ATGGGGTGAG CAGTTTCTTT ATCACTTACA AGCCTACTTA TAAGAAACTC 2280 AAAGGGTTGA GCCTGAACGC GGTGTTTAAT AATGTTTTTA ACCAACAATA TATTGATCAA 2340 GCAAGCCCGG TGATGAGCCC TGATGAACCC AATCAAGACA AATACGCAAG GGGCATGGCA 2400 GAGCCTGGCT TTAACGCTAG GTTTGAAATT TCTTATAAGT TTTAA 2445

(2) INFORMATION FOR SEQUENCE NO. 52

184 (i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 1584 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular (ii) MOLECULA TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE : NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) NAME / KEY: various characters (B) LOCATION 1 ... 1584 (xi) SEQUENCE DESCRIPTION: Sequence no. 52:

ATGAAACAAA ATTTAAAGCC ATTCAAAATG ATTAAGGAAA ATTTAATGAC ACAATCTCAA 60 AAAGTAAGAT TCTTAGCCCC TTTGAGCCTA GCGTTAAGCT TGAGCTTCAA TCCAGTGGGC 120 GCTGAAGAAG ATGGGGGCTT TATGACCTTT GGGTATGAAT TAGGTCAGGT GGTCCAGCAA 180 GTGAAAAACC CGGGTAAAAT CAAAGCCGAA GAATTAGCGG GCCTGTTAAA CTCTACCACG 240 ACAAACAACA CCAATATCAA TATTGCAGGC ACAGGAGGGA ATGTCGCCGG GACTTTGGGC 300 AACCTTTTTA TGAACCAATT GGGCAATTTG ATTGATTTGT ATCCTACTTT GAAAACTAAT 360 AATCTTCACC AATGCGGTAG CACTAATAGC GGTAATGGCG CTACTGCTGC CGCTGCTACT 420 AACAATAGCC CTTGTTTCCA AGGTAACCTG GCTCTTTATA ACGAAATGGT TGACTCTATC 480 AAAACTTTGA GTCAAAACAT CAGCAAGAAC ATCTTTCAAG GCGACAACAA CACCACGAGC 540 GCTAATCTCT CCAACCAGCT CAGTGAGTTG AACACCGCTA GCGTTTATTT GACTTACATG 600 AACTCGTTCT TAAACGCCAA CAACCAAGCG GGTGGGATTT TTCAAAACAA CACCAATCAA 660 GCTTACGAGA ATGGTGTTAC CGCTCAACAA ATCGCTTATG TCCTAAAGCA AGCTTCAATC 720 ACTATGGGGC CAAGCGGTGA TAGTGGGGCT GCGGGAGCGT TTTTAGACGC CGCTTTAGCC 780 CAACATGTTT TCAACTCGGC TAACGCTGGG AACGATTTGA GCGCTAAGGA ATTCACTAGC 840 TTGGTGCAAA ACATCGTCAA TAATTCTCAA AACGCTTTAA CGCTAGCCAA CAACGCTAAC 900 ATCAGCAATT CAACAGGCTA TCAAGTGAGC TATGGTGGGA ATATTGATCA AGCGCGCTCT 960 ACCCAACTGT TAAACAACAC CACAAACACT TTGGCTAAAG TTACCGCTCT AAACAACGAG 1020 CTTAAAGCTA ACCCATGGCT TGGGAATTTC GCTGCTGGTA ACAGCTCTCA AGTGAATGCG 1080 TTTAACGGGT TTATCACTAA AATCGGTTAT AAGCAATTCT TCGGGGAAAA CAAGAATGTG 1140 GGCTTACGCT ACTACGGGTT CTTCAGCTAT AACGGCGCGG GCGTGGGTAA TGGCCCCACT 1200 TACAATCAAG TCAATCTGCT CACTTATGGG GTGGGGACTG ATGTGCTTTA CAATGTGTTT 1260 AGCCGCTCTT TTGGCAGTAG GAGTCTTAAT GCGGGCTTCT TTGGGGGGAT CCAACTCGCA 1320

185

GGGGACACTT ACATCAGCAC GCTAAGAAAC AGCCCTCAGC TTGCGAGCAG ACCTACAGCG ACAAAATTCC AATTCTTGTT TGATGTGGGC TTACGCATGA ACTTTGGTAT CTTGAAAAAA GACCTAAAAA GCCATAACCA GCATTCTATA GAAATCGGTG TGCAAATCCC TACGATTTAC AACACTTACT ATAAAGCTGG TGGCGCTGAA GTGAAATACT TCCGCCCTTA TAGCGTGTAT TGGGTCTATG GCTACGCCTT CTAA (2) INFORMATION FOR SEQ ID NO. 53:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 1380 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular (ii) MOLECULAR TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE : NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) NAME / KEY: various characters (B) LOCATION 1 ... 1380 (xi) SEQUENCE DESCRIPTION: Sequence no. 53:

GTGGTGTTAT TAACAATGAC AAAACGACTT TTTAAAGGGT TGTTAGCGAT TTCTCTTGCG GTGAGTTTGC ATGGTGGTGA AGTTAAGGAA AAAAAGCCGG TCAAGCCGGT CAAAGAAGAT CCGCAAGAAT TAGCGGCTAA AAGGGTGGAA GCGTTCAGTC GTTTCTCTAA TGTGGTTACA GAAATTGAAA AAAAGTATGT GGATAAGATC AGTATTTCTG AGATCATGAC TAAAGCGATT GAAGGCTTAC TCTCTAATTT GGACGCGCAT TCAGCGTATT TGAATGAAAA GAAGTTTAAG GAATTTCAGG CCCAAACCGA GGGCGAATTT GGGGGGCTTG GGATCACGGT GGGCATGCGC GATGGCGTTT TGACCGTTAT TGCACCTTTA GAGGGCACTC CAGCTTACAA GGCTGGGGTT AAATCAGGCG ATAGCATTTT AAAAATCAAT AACGAAAGCA CGCTGAGCAT GAGCATTGAT GATGCGGTTA ATCTCATGCG CGGCAAGCCA AAAACCTCTA TTCAGATCAC TGTTGTTAGG AAAAATGAGC CAAAACCCTT GGTATTTAAT ATCGTTAGGG ATATTATCAA GATCCCCTCT GTCTATGTGA AAAAGATTAA AGACACACCT TATTTGTACG TGAGAGTCAA TTCTTTTGAT AAAAATGTTA CCAAATCGGT TTTAGACGGC TTGAAGGCTA ACCCTAACAT TAAGGGCGTT GTGTTGGATT TGAGGGGGAA TCCTGGAGGG CTATTAAACC AGGCGGTAGG CTTGTCTAAC CTTTTCATTA AAGAGGGGGT TTTAGTCTCT CAAAGAGGCA AAAATAAGGA GGAAAACTTA GAATACAAGG CTAATGGCAG AGCCCCTTAT ACCAATTTAC CTGTTGTGGT GTTAGTCAAT

1380

1440

1500

1560

1584

120

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360

420

480

540

600

660

720

780

840

900

186 ggcggttcag cgagcgcgag cgagatcgtc gcaggggcac tgcaagatca caagcgagcc ATCATTATCG GTGAAAAAAC CTTTGGTAAG GGAAGCGTGC AAGTGTTGCT CCCTGTCAAT AAAGACGAAG CCATTAAAAT CACGACCGCG CGCTATTATT TGCCGAGCGG GCGCACCATT CAAGCTAAGG GGATCACGCC TGATATTGTG ATTTATCCGG GTAAAGTGCC AGAAAATGAA AATAAATTCA GTTTGAAAGA AGCGGATTTA AAACACCATT TAGAGCAAGA GCTTAAAAAA CTTGATGATA AAACCCCTAT TTCCAAAGAG GCGGATAAAG ACAAGAAAAG CGAAGAGGAA AAAGAGGTTA CTCCTAAAAT GATCAATGAT GATATTCAGC TAAAAACCGC TATTGACAGC TTGAAAACCT GGTCTATCGT AGATGAGAAA ATGGATGAAA AAGTGCCTAA GAAGAAATAA ( 2) INFORMATION FOR SEQUENCE NO. 54:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 315 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular (ii) MOLECULAR TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE : NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) NAME / KEY: various characters (B) LOCATION 1 ... 315 (xi) SEQUENCE DESCRIPTION: Sequence no. 54:

TTGCTTTTGC ACCCCTTGCA TGCTCATGCA CAAGTGCTTG GCTTCACAAA CCACGATCAC GCCCCTTGGC TCTATGATTT CATCAAAAGT TTCTGCAATT TGAGTGGTCA GCCTTTCTTG GATTTGCAGG CGTTTGCTAT AAATTTCAAT GAGTTTAGCG ATCGCGCTAA TGCCTACAAT CTTTTCCTTA GGGATATATC CCACGCTAAT ATTCCCAAAA AAAGGGAGCA AATGGTGCTC GCAAGTGGAG TAAAATTCAA TGTTTTGAGC CACTATCATT TCATCGCAAA CGCCTTGAAA ATACGCGCTT TTTAA

960

1020

1080

1140

1200

1260

1320

1380

120

180

240

300

315 (2) INFORMATION FOR SEQUENCE NO. 55:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 498 base pairs (B) TYPE: nucleic acid

187 (C) NUMBER OF FIBERS: two (D) TOPOLOGY: circular (ii) MOLECULA TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) NAME / KEY: various characters (B) LOCATION 1 ... 498 (xi) SEQUENCE DESCRIPTION: Sequence no. 55:

ATGATTGAAC TAATCTTACA CAATAAGTCC ATACAAATTG ATGAAACATT GCTGAATGTA 60 AAAGAGCATT TAGAAAAGTT TTATTCAAAC AAAGAACAAG AGACAATCGC AAAAACCTTA 120 GAGAGCCAAA CAGAGCTTAC TTGCAGTTAT TTATTGGATA AAGATTTTTC ATTGCTAGAA 180 AAGCATTTAG AAAATAGCTT AGGGCATTTT ACTTTTGAGA GTGAGTTTGC CCTACTAAAA 240 GACAAAGAGC CTTTGAATTT AGCTCAAATC AAACAAATCG GTGTTTTAAA GGTTATTACC 300 TATGAAATGA CACAAGCCTT AAAAAATCAA ATCATTCATT TAACGCAAAT TGTCAATGAA 360 GAAAATTTAG AGTTTGATGA AGAACTTGTT ATTTATCACT TAAATTTTAA GCTCAATCAA 420 AATACTTACA AAGTGTTAGC GAAATTTTGC GTATTAAAAA AGAAAGGAAC ATTGCATGAA 480 AAATTTAAGG CATTTTAG 498 (2) INFORMATION FOR SEQUENCE NO. 56:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 642 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular (ii) MOLECULAR TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE : NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori

188 (ix) SIGN:

(A) NAME / KEY: various characters (B) LOCATION 1 ... 642 (xi) SEQUENCE DESCRIPTION: Sequence no. 56:

ATGGATACCG AAACACAAGA AAAGTTTTTA GCGTATTTGT TTGAAAAAGC TTTACAAAAA 60

AATCTACAAG CTTATTGGAT AACAACAACT GAAACTAAGA ATGAATTAAC AAGAGAAGAG 120

TTTTCAAATT TAATAAGAAA AACAATGATT GAACTAATCT TACACAATAA GTCCATACAA 180

ATTGATGAAA CATTGCTGAA TGTAAAAGAG CATTTAGAAA AGTTTTATTC AAACAAAGAA 240

CAAGAGACAA TCGCAAAAAC CTTAGAGAGC CAAACAGAGC TTACTTGCAG TTATTTATTG 300

GATAAAGATT TTTCATTGCT AGAAAAGCAT TTAGAAAATA GCTTAGGGCA TTTTACTTTT 360

GAGAGTGAGT TTGCCCTACT AAAAGACAAA 420 GAGCCTTTGA ATTTAGCTCA AATCAAACAA 420

ATCGGTGTTT TAAAGGTTAT TACCTATGAA ATGACACAAG CCTTAAAAAA TCAAATCATT 480

CATTTAACGC AAATTGTCAA TGAAGAAAAT TTAGAGTTTG ATGAAGAACT TGTTATTTAT 540

CACTTAAATT TTAAGCTCAA TCAAAATACT TACAAAGTGT TAGCGAAATT TTGCGTATTA 600

AAAAAGAAAG GAACATTGCA TGAAAAATTT AAGGCATTTT AG 642 (2) INFORMATION FOR SEQUENCE NO. 57:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 762 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular (ii) MOLECULA TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE : NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) NAME / KEY: various characters (B) LOCATION 1 ... 762 (xi) SEQUENCE DESCRIPTION: Sequence no. 57:

ATGGCGATCT CTATTAAAAG CCCAAAAGAA ATCAAAGCCC TAAGAAAAGC CGGGGAATTA 60 ACCGCTCAAG CGTTAGCCCT TTTAGAGCGA GAAGTAAGGC CTGGGGTTTC ACTTTTAGAG 120

189

CTGGATAAAA TGGCTGAAGA TTTTATCAAA TCCTCGCATG CTAGGCCTGC TTTTAAGGGG CTCTATGGTT TCCCTAACTC TGTGTGCATG TCCTTAAATG AGGTGGTTAT TCATGGTATT CCTACGGATT ATGTTTTACA AGAAGGGGAT ATTATAGGCT TGGATTTGGG GGTGGAGGTG GATGGCTATT ATGGCGATTC AGCCCTCACG CTTCCCATAG GCGCGATAAG CCCGCAAGAT GAAAAATTGC TCGCTTGCTC TAAAGAGAGC TTGATGCATG CCATTAGCTC AATTAGAGTG GGCATGCATT TTAAAGAGTT GAGTCAGATT TTAGAGGGCG CTATTACAGA AAGGGGCTTT GTGCCTTTGA AGGGATTTTG CGGGCATGGC ATTGGTAAAA AGCCCCATGA AGAGCCAGAA ATCCCCAACT ACCTAGAAAA AGGCGTCAAA GCTAATAGCG GCCCTAAAAT CAAAGAGGGC ATGGTGTTTT GTTTAGAGCC TATGGTGTGT CAAAAACAAG GCGAGCCTAA AATACTAGCG GATAAGTGGA GCGTGGTTTC AGTGGATGGA CTTAACACAA GCCACCATGA GCATACTATC GCCATAGTTG GCAATAAAGC AGTGATTCTT ACGGAGCG. 58:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 744 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular (ii) MOLECULA TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE : NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix) SIGN: (A) NAME / KEY: different characters (B) PLACEMENT 1 ... 745

(xi) SEQUENCE DESCRIPTION: SEQ ID NO. 58:

AAGCCCAAAA GAAATCAAAG CCCTAAGAAA AGCCGGGAAT TAACCGCTCA AGCGTTAGCC CTTTTAGAGC GAGAAGTAAG GCCTGGGGTT TCACTTTTAG AGCTGGATAA AATGGCTGAA GATTTTATCA AATCCTCGCA TGCTAGGCCT GCTTTTAAGG GGCTCTATGG TTTCCCTAAC TCTGTGTGCA TGTCCTTAAA TGAGGTGGTT ATTCATGGTA TTCCTACGGA TTATGTTTTA CAAGAAGGGG ATATTATAGG CTTGGATTTG GGGGTGGAGG TGGATGGCTA TTATGGCGAT TCAGCCCTCA CGCTTCCCAT AGGCGCGATA AGCCCGCAAG ATGAAAAATT GCTCGCTTGC TCTAAAGAGA GCTTGATGCA TGCCATTAGC TCAATTAGAG TGGGCATGCA TTTTAAAGAG TTGAGTCAGA TTTTAGAGGG CGCTATTACA GAAAGGGGCT TTGTGCCTTT GAAGGGATTT TGCGGGCATG GCATTGGTAA AAAGCCCCAT GAAGAGCCAG AAATCCCCAA CTACCTAGAA

180

240

300

360

420

480

540

600

660

720

762

120

180

240

300

360

420

480

540

190

AAAGGCGTCA AAGCTAATAG CGGCCCTAAA ATCAAAGAGG GCATGGTGTT TTGTTTAGAG 600

CCTATGGTGT GTCAAAAACA AGGCGAGCCT AAAATACTAG CGGATAAGTG GAGCGTGGTT 660

TCAGTGGATG GACTTAACAC AAGCCACCAT GAGCATACTA TCGCCATAGT TGGCAATAAA 720

GCAGTGATTC TTACGGAGCG TTAA 744 (2) INFORMATION FOR SEQUENCE NO. 59:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 1023 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular (ii) MOLECULA TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE : NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix) SIGN: (A) NAME / KEY: different characters (B) PLACEMENT 1 ... 1022

(xi) SEQUENCE DESCRIPTION: SEQ ID NO. 59:

ATGTATCGTA AAGATTTGGA TAATTACTTA AAACAGCGCC TCCCTAAAGC GGTGTTTTTG 60 TATGGGGAGT TTGATTTTTT CATCCATTAT TATATTCAAA CGATTAGCGC GCTTTTTAAA 120 GGCAATAACC CTGACACAGA AACTTCGCTT TTTTATGCGA GCGATTATGA AAAAAGCCAG 180 ATTGCGACCC TTTTAGAGCA GGATTCTTTA TTTGGAGGGA GCAGTTTAGT tattttaaaa 240 CTGGATTTTG CATTGCATAA GAAATTTAAG GAAAATGATA TCAATCCTTT TTTAAAAGCT 300 TTAGAGCGGC CTAGCCATAA TAGGCTTATC ATAGGGCTTT ATAATGCTAA AAGCGACACC 360 ACAAAATACA AATACACTAG CGAAATTATC GTTAAATTTT TCCAAAAAAG CCCCTTGAAA 420 GATGAAGCCA TTTGCGTGCG CTTTTTTACC CCTAAAGCGT GGGAGAGTTT GAAATTCTTG 480 CAAGAAAGGG CTAATTTTTT GCATTTAGAC ATCAGCGGCC ATCTTTTAAA CGCTCTTTTT 540 GAAATTAATA ACGAAGATTT AAGCGTTTCG TTTAACGATT TAGACAAGCT AGCGGTTTTA 600 AACGCGCCCA TCACTTTAGA AGACATTCAA GAATTAAGCT CCAATGCGGG GGATATGGAT 660 TTGCAAAAGC TCATTTTAGG GCTTTTTTTG AAAAAAAGCG TCCTTGATAT TTATGATTAT 720 TTGTTAAAAG AGGGCAAAAA GGATGCGGAT ATTTTAAGGG GGTTAGAGCG CTATTTTTAC 780 CAGCTTTTTT TATTTTTCGC CCACATTAAA ACGACCGGTT TAATGGACGC TAAAGAGGTC 840 TTAGGCTACG CTCCTCCTAA AGAGATTGTA GAAAATTACG CTAAAAACGC CCTGCGTTTG 900 AAAGAAGCCG GCTATAAGAG GGTTTTTGAA ATTTTTAGGT TATGGCACCT TCAAAGCATG 960

191

CAAGGGCAAA AGGAATTGGG CTTTTTGTAT TTGACCCCCA TTCAAAAAAT CATTAACCCT 1020 TGA 1023 (2) INFORMATION FOR SEQUENCE NO. 60:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 603 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular (ii) MOLECULAR TYPE: DNA (genomic) (iii, HYPOTHETICAL: NO (iv) ANTI-SENSE : NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix) SIGN: (A) NAME / KEY: different characters (B) PLACEMENT 1 ... 603

(xi) SEQUENCE DESCRIPTION: SEQ ID NO. 60:

GTGTTTATGA CAAGCGCTCT GTTAGGCTTA GTGGTTTTGT TGCAAAAAAG TTCTAGCATC TCTTTATTTG GCGCTAAAGG GCCCGCAAGC TTATTGTTTG TCATCAACAC CATCGCTTTG AGCGTTTTAG ATGAAACTAA AACCAATAAA ACGCTCAACC CTACGCTTAA TCCCACATTA CCCACTAATC CTTTAATGCC TACACAAACG ACGCCTTTTG TTGAAAGCCC CAAACAGAAT AATGGTATAA AGGGTGTTGA AAAAAACAAA CAAAAGCCTA AAACGCATGC GACAACCAAC TAA

CAAATTGTTT TAGCGGTATT GATTGTGGTG 60 GGCTTAGGGG CTTATAGCGG AAGCAACGAT 120 TTTATGGCGA AATTGACCAT GTTTTTAGGT 180 GGCTATTTTT ACAACAAAGA ATACGGCAAG 240 GAGCTTTCGC CCTTAGTCCC TGCCACCGGC 300 AACCCAACGC TCAACCCTTT AGAGCAAGCC 360 CCTAAAGAGC TTCCTAAAGA GCCAGCCAAA 420 GAAAAGAATG AAAAGAATGA TGCCAAAGAA 480 GAGAACGCCA AAACGCCCCC AACCACCCAC 540 GCCCATACCA ACCAAAAAAA GGATGAAAAA 600 603

(2) INFORMATION FOR SEQUENCE NO. 61:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 480 base pairs (B) TYPE: nucleic acid (C) FIBERS: two

192 (D) TOPOLOGY: circular (ii) MOLECULA TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix) SIGN: (A) NAME / KEY: Differently letters (B) PLACEMENT 1. . . 480

(xi) SEQUENCE DESCRIPTION: SEQ ID NO. 61:

ATGCGTTCTC CAAATTTAGA AAAAGAAGAA ACTGAAATCA TAGAAACGCT TCTTGTGCGT GAAAAAATGC GTTTATGCCC CTTGTATTGG CGCATCTTAG CGTTTTTAAT CGATAGTTTA TTGGTGGCGT TTTTATTGAG CGATCTTTTA AGGGCATGCG CTTTTTTACA TTCTTTATAT TGGCTGACTA ACCCCATTTA TTACAGCGCG TTTGTTGTGA TGGGTTTTAT CATCTTGTAT GGCGTTTATG AAATCTTTTT TGTGTGTTTG TGCAAGATGA GTTTGGCTAA ACTGGTTTTT AGGATTAAGA TCATTGATAT TTATTTAGCG GATTGCCCCA GTAGGGCTAT TTTATTGAAG CGTTTAGGGT TAAAAATCGT GGTTTTTCTA TGCCCCTTTT TATGGTTTGT GGTGTTTAAA AACCCCTATC ATAGGGCATG GCATGAAGAA AAÄAGCAAAA GTCTTTTGGT GTTGTTTTAA (2 ) INFORMATION FOR SEQUENCE NO. 62:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 705 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular (ii) MOLECULA TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE : NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori

120

180

240

300

360

420

480 (ix)

193 (A) NAME / KEY: miscellaneous characters (B) LOCATION 1 ... 705 (xi) SEQUENCE DESCRIPTION: Sequence no. 62:

TTGAATACGG ACTTTAGCCA TATCACCGAT ATTGAGGGCA TGCGTTTTGT TAATGAAGAA 60

GACGCTTTAA ACAAATTGAT TAATGAAATC CACACGCGCC ACATTGATTT AAAAGATTCC 120

ATCATGCTCG CTTTGAGTTT TAACGCCTTG TATTTAGCTA ACGCTTTAGC GCAAAAATTT 180

GGGGCGACTT ATGATATACT TTTTTTAGAA CCTATCTTAG CCCCTTTAAA CTCAAAGTGT 240

GAAATCGCTT TAGTGAGTGA AAGCATGGAT ATAGTGATGA ATGAAAGTTT AATCAATTCC 300

TTTGACATCG CTTTAGACTA TGTTTATGGG GAAGCCAAGC GGGCTTATGA AGAAGACATT 360

CTGTCTCACA TCTATCAGTA TCGCAAAGGC AATGCGATCA AAAGCCTAAA AGATAAAAAT 420

ATTTTTATCG TAGATAGGGG GATTGAGACC GGGTTTAGAG CAGGGTTAGG CGTGCAAACT 480

TGTTTGAAAA AAGAATGCCA AGACATTTAT ATTTTAACCC CCATTCTCGC GCAAAATGTC 540

GCTCAAGGCT TAGAAAGCTT GTGCGATGGG GTGATTAGCG TGTATCGCCC TGAATGTTTT 600

GTCTCTGTGG AACACCATTA TAAAGAACTC AAGCGATTAA GCAATGAAGA AATTGAAAAA 660

TACTTGGGCG CTAACAACGC GCCCAATCTC AAAAAGGAAC ATTAA 705 (2) INFORMATION FOR SEQUENCE NO. 63:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 864 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular (ii) MOLECULA TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE : NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix) SIGN: (A) NAME / KEY: different characters (B) PLACEMENT ... 864

(xi) SEQUENCE DESCRIPTION: SEQ ID NO. 63:

TTGAAACAAA GCGAAATGGC CATGGAATTT AATGATCCTA GGATGCGTTT TTTTATTGGC 60 GATGTCAGGG ATTTAGAACG CTTGAATTAC GCTTTAGAGG GCGTGGATAT

194

AACATCATGG GAGCGAGCAA TGTGATTAAC GCATGCTTAA AAAATGAAAT CAGCCAGGTT ATTGCCCTAA GCACCGATAA AGCCGCTAAC CCCATTAACC TCTACGGCGC AACCAAATTG TGCAGCGACA AGCTCTTTGT GAGCGCGAAC AACTTTAAAG GCCCTTCTCA AACGCAATTT GGCGTGGTGC GTTATGGTAA TGTGGTGGGG AGTCGTGGGA GCGTGGTGCC GTTTTTTAAA AAATTAGTCC AAAACAAAGC GAGTGAAATC CCCATTACCG ATATTCGCAT GACACGATTT TGGATCACCT TAGATGAGGG GGTTTCTTTT GTGCTTAAAA GCTTGAAAAG AATGCATGGG GGGGAAATTT TTGTGCCTAA AATCCCCAGC ATGAAAATGA TTGATCTCGC CAAAGCCCTA GCCCCCAATA TCCCTACTAA AATCATAGGG ATTCGCCCGG GCGAAAAACT CCATGAAGTG ATGATCCCTA AAGATGAAAG CCATTTAGCC CTAGAATTTG AAGACTTTTT TATTATTCAG CCCACTATAA GCTTCCAAAC 64:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 606 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular (ii) MOLECULA TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE : NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) NAME / KEY: various characters (B) LOCATION 1 ... 606 (xi) SEQUENCE DESCRIPTION: Sequence no. 64:

ATGCGTTTGC ACACTGCCTT TTTTGGTATT AATTCGTTGC TTGTCGCCAC TCTTTTGATA AGCGGTTGCA GTCTCTTTAA AAAGCGTAAC ACTAACGCTC AGCTAATCCC CCCTTCAGCT AACGGGTTGC AAGCCCCCAT TTATCCCCCA ACCAATTTCA CCCCCAGAAA GAGCATTCAG CCTCTCCCAA GCCCTCGCCT TGAGAATAAC GATCAGCCCA TCATTAGCTC TAATCCCACT AACGCTATCC CTAACACCCC CATTCTCACG CCCAATAATG TCATTGAGTT GAATGCGGTG GGCATGGGTG TGGCTCCAGA ATCCACCATT TCGCCCTCTC AAGCTCTAGC TTTAGCTAAG CGAGCGGCTA TTGTTGATGG CTACCGCCAG TTGGGTGAAA AAATGTATGG CATCAGAGTG AACGCTCAAG ACACCGTCAA AGACATGGTT TTACAAAATT CCGTGATTAA AACGAGAGTG

240

300

360

420

480

540

600

660

720

780

840

864

120

180

240

300

360

420

480

195

AATGCCCTCA TTCGTAACGC TGAAATCACT GAGACTATCT ATAAAGACGG CTTGTGCCAG 540 GTAAGCATGG AGCTTAAATT AGACGGCAGG ATTTGGTATC GTATTTTGAG CGGATCGAGA 600 GGATAA 606 (2) SEQ ID NO. 65:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 1068 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular (ii) MOLECULA TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv, ANTI-SENSE : NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) NAME / KEY: various characters (B) LOCATION 1 ... 1068 (xi) SEQUENCE DESCRIPTION: Sequence ô. 65:

ATGAGTTATA CTATTAATAA ACGCTTTTCT GTGGGTGTGG GTTTAAGGGG GCTTTATGCG 60 ACCGGGAGCT TTAATAACAC CGTTTATGTG CCTTTAGAGG GCGCTTCAGT TTTGAGCGCG 120 GAGCAAATCT TAAACTTACC CAACAATGTT TTTGCCGATC AAGTGCCAAG TAACATGATG 180 ACTTTATTAG GCAATATTGG CTACCAACCA GCGCTTAATT GCCAAAAAGC CGGTGGGGAC 240 ATGAGTGATC AGAGCTGTCA AGAGTTTTAC AACGGCTTGA AAAAAATCAT GGGTTATAGC 300 GGTTTAATCA AAGCGAGCGC GAATCTTTAT GGCACGACTC AAGTCGTGCA AAAATCTAAC 360 GGACAAGGCG TATCGGGGGG GTATAGAGTG GGTTCGAGTT TGCGTGTGTT TGATCATGGC 420 ATGTTTTCTG TGGTGTATAA TTCTTCAGTT ACCTTTAACA TGAAAGGCGG TTTGGTGGCT 480 ATCACAGAGC TTGGCCCTTC TTTAGGGAGC GTTTTGACTA AAGGCAGCTT GAATATCAAT 540 GTTTCACTCC CCCAAACTTT AAGCTTAGCC TACGCCCACC AATTTTTTAA AGATCGCCTA 600 AGGGTTGAAG GGGTGTTTGA GCGCACTTTT TGGAGTCAAG GGAATAAATT TTTAGTCACC 660 CCTGATTTTG CGAACGCCAC TTACAAGGGC TTGAGCGGGA CGGTGGCTTC CTTGGACTCT 720 GAAACGCTTA AAAAAATGGT AGGCCTAGCG AATTTTAAAA GCGTGATGAA CATGGGGGCT 780 GGCTGGAGGG ACACCAACAC CTTTAGATTA GGGGTAACTT ACATGGGTAA AAGCTTGCGT 840 TTAATGGGCG CTATTGATTA TGATCAAGCC CCAAGCCCCC AAGACGCGAT AGGCATTCCG 900 GACTCTAATG GCTATACCGT GGCTTTTGGG ACTAAATACA ATTTTAGGGG CTTTGATTTG 960 GGCGTAGCGG GGAGTTTCAC TTTTAAGAGC AACCGCTCCA GTTTGTATCA ATCCCCAACT 1020

196

ATTGGGCAAT TGAGAATCTT TAGCGCCTCT TTAGGCTATC GCTGGTAA 1068 (2) 66:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 1764 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular (ii) MOLECULA TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE : NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix) SIGN: (A) NAME / KEY: different characters (B) PLACEMENT 1 ... 1764

(xi) SEQUENCE DESCRIPTION: SEQ ID NO. 66:

ATGAAAAACT TTTCCCCACT CTATTGTCTT AAAAAGCTCA AAAAACGCCA TTTAATCGCT 60 CTGAGTCTGC CCTTGCTTTC TTATGCGAAT GGCTTTAAAA TCCAAGAGCA AAGCTTGAAT 120 GGCACGGCTT TAGGCTCGGC GTATGTCGCT GGGGCTAGGG GTGCTGACGC TTCTTTTTAC 180 AACCCGGCTA ACATGGGCTT TACTAACGAT TGGGGCGAAA ACAGAAGCGA ATTTGAAATG 240 ACCACCACCG TGATCAATAT CCCGGCCTTT AGCTTTAAAG TCCCTACGAC CAATCAAGGC 300 TTATATTCGG TAACAAGTTT AGAAATTGAT AAAAGCCAAC AAAATATTTT AGGCATCATC 360 AACACTATAG GGTTAGGCAA TATCCTTAAA GCGCTTGGCA ATACGGCCGC TACCAATGGC 420 TTATCACAAG CTATCAATCG TGTTCAAGGG CTTATGAACT TAACCAATCA AAAAGTCGTA 480 ACCCTCGCTT CAAAACCTGA CACTCAAATC GTGAATGGCT GGACAGGCAC GACTAATTTT 540 GTTTTACCTA AATTCTTTTA TAAAACGCGC ACGCATAACG GCTTCACTTT TGGGGGGAGT 600 TTTACCGCTC CTAGTGGGTT GGGTATGAAA TGGAATGGTA AGGGGGGGGA ATTTTTGCAT 660 GACGTGTTTA TCATGATGGT AGAGCTTGCC CCTAGCATGA GTTATACTAT TAATAAACGC 720 TTTTCTGTGG GTGTGGGTTT AAGGGGGCTT TATGCGACCG GGAGCTTTAA TAACACCGTT 780 TATGTGCCTT TAGAGGGCGC TTCAGTTTTG AGCGCGGAGC AAATCTTAAA CTTACCCAAC 840 AATGTTTTTG CCGATCAAGT GCCAAGTAAC ATGATGACTT TATTAGGCAA TATTGGCTAC 900 CAACCAGCGC TTAATTGCCA AAAAGCCGGT GGGGACATGA GTGATCAGAG CTGTCAAGAG 960 TTTTACAACG GCTTGAAAAA AATCATGGGT TATAGCGGTT TAATCAAAGC GAGCGCGAAT 1020 CTTTATGGCA CGACTCAAGT CGTGCAAAAA TCTAACGGAC AAGGCGTATC GGGGGGGTAT 1080 AGAGTGGGTT CGAGTTTGCG TGTGTTTGAT CATGGCATGT TTTCTGTGGT GTATAATTCT 1140

197

TCAGTTACCT TTAACATGAA AGGCGGTTTG GTGGCTATCA CAGAGCTTGG CCCTTCTTTA GGGAGCGTTT TGACTAAAGG CAGCTTGAAT ATCAATGTTT CACTCCCCCA AACTTTAAGC TTAGCCTACG CCCACCAATT TTTTAAAGAT CGCCTAAGGG TTGAAGGGGT GTTTGAGCGC ACTTTTTGGA GTCAAGGGAA TAAATTTTTA GTCACCCCTG ATTTTGCGAA CGCCACTTAC AAGGGCTTGA GCGGGACGGT GGCTTCCTTG GACTCTGAAA CGCTTAAAAA AATGGTAGGC CTAGCGAATT TTAAAAGCGT GATGAACATG GGGGCTGGCT GGAGGGACAC CAACACCTTT AGATTAGGGG TAACTTACAT GGGTAAAAGC TTGCGTTTAA TGGGCGCTAT TGATTATGAT CAAGCCCCAA GCCCCCAAGA CGCGATAGGC ATTCCGGACT CTAATGGCTA TACCGTGGCT TTTGGGACTA AATACAATTT TAGGGGCTTT GATTTGGGCG TAGCGGGGAG TTTCACTTTT AAGAGCAACC GCTCCAGTTT GTATCAATCC CCAACTATTG GGCAATTGAG AATCTTTAGC GCCTCTTTAG GCTATCGCTG GTAA (2) NO. 67:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 618 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular (ii) MOLECULA TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE : NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) NAME / KEY: various characters (B) LOCATION 1 ... 618 (xi) SEQUENCE DESCRIPTION: Sequence no. 67:

TTGATTTTTA GATTTTTCTT AATCTTAAGC CTTTTAAAAG GGGTTTTACT GGCCAAAAAG GATTGGAATT TTTTCAAACC TTTAGAGCCT ACTAAAAAAT ATTTTGGCTC TTTTAAAATC GGCTATCTTT ACCAACATGC AGAAACGACT AAAAGATTCC CCATCCGCCC TAAAAACCGC CCGCCTATTT TAATGGATAA AATTTACCAT GACGCTTCTT TGGGTTTTGA CGCAGGGTAT GTTTTGAAAA AGAAAGCTTT ATTGGGGGGG TATTTGGATG CAGGAATGGG CGATTCGTAT TTCATGAGCG CTGGGCTAGT CGCTGGGGTG AGGCTTTTTA AGGGGTGGGT TATCCCTAAA ATCGCCTTAG GCTATCAGCT TCAAATTTTA GGGGCTAAGA TTGATAAGTA TCAATTCAAT ATCCAATCAG CGGTGGGGAG TGTGGGCTTG TTTTTCAATG CGGCTAAAAA TTTTGGCTTG AGTATAGAAG CAAGGGGCGG TATCCCTTTT TATTTCATTC AGAGCAGGTT TTCTAAGGCT

1200

1260

1320

1380

1440

1500

1560

1620

1680

1740

1764

120

180

240

300

360

420

480

540

198

TTCGGCACGC CACGATTGAA TATCTATTCT GTTGGTATCA CATTCACTTT TTATGACTTT 600 ACGAGATTTT TAGGGTAA 618 (2) INFORMATION FOR SEQUENCE NO. 68:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 762 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular (ii) MOLECULA TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE : NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) NAME / KEY: various characters (B) LOCATION 1 ... 762 (xi) SEQUENCE DESCRIPTION: Sequence fi. 68:

TTGTGGCATG CTGCCTTTAG CGTTGGCGAG TGGGGATGGA ACGGCGATGA AATCCCCTAT 60 AGGGATTGCG ATGAGTGGGG GCTTGATGAT TTCTATGGTG TTAAGCCTAC TGATTGTGCC 120 GGTGTTTTAT CGTTTGCTCG CTCCCATAGA CGACAAAATC AAGCGGTTTT ATCAAAACCA 180 AAAAGCTTTA GAATGAAAAA AATTGCTTTC ATTTTGGCTT TATGGGTGGG CTTGTTAGGG 240 GCGTTTGAGC CTAAAAAAAG TCATATTTAT TTTGGGGCTA TGGTGGGTTT AGCCCCTGTT 300 AAAATAACCC CAAAACCGGC TAGTGATTCT TCTTATACGG CTTTTTTATG GGGGGCTAAA 360 GGGGGGTATC AATTCGCTTT TTTTAAAGCT CTAGCGTTAA GGGGTGAATT TTCCTACCTT 420 ATGGCGATCA AACCCACCGC ACTGCACACG ATTAACACTT CTTTATTGAG TTTAAATATG 480 GATGTGTTGA GCGATTTTTA CACTTATAAA AÄATACAGCT TTGGGGTGTA TGGGGGGCTT 540 GGGATAGGGT ATTTTTATCA AAGCAACCAT TTAGGCATGA AAAATAGTTC GTTTATGGGT 600 TATAACGGCT TGTTTAATGT GGGGCTTGGC AGCACGATCG ATCGCCACCA CCGCGTAGAG 660 CTTGGGGCTA AGATCCCTTT TTCAAAGACT AGAAATTCTT TTAAAAATTC TTATTTTTTA 720 GAGAGCGTTT TTATCCATGC GGCTTATAGT TATATGTTTT AA 762 (2) INFORMATION FOR SEQ ID NO. 69:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 1239 base pairs

199 (B) TYPE: nucleic acid (C) NUMBER OF FIBERS: two (D) TOPOLOGY: circular (ii) MOLECULA TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE :

(A) ORGANISM: Helicobacter pylori (ix)

(A) NAME / KEY: different characters (B) LOCATION 1 ... 1239 (xi) SEQUENCE DESCRIPTION: Sequence £. 69:

ATGGAATCAG TAAAAACAGT AAAAACAAAT AAAGTTGGCA AAAACACAGA GACAGCTAAC 60 ACAGAGGCAA GTAAAGAGAC TCATTTTAAA CAAGCGAGTG CCATTACAAA TACGCTCCGA 120 TCAATTGGTG GGATTTTTAC AAAAATTGCA AAGAAAGTTA GAGAACTTGT GAAAAAACAT 180 CCCAAGAAAA GCAGTGTGGC ATTAGTAGTA TTGACCCATA TTGCGTGCAA GAGGGCAAAA 240 GAATTGGACG ATAAAGTCCA AGATAAATCC AAACAAGCTG AAAAAGAAAA TCAAATCAAT 300 TGGTGGAAAT ATTCAGGATT AACÄATAGCG GCAAGTTTAT TATTAGCCGC TTGTAGCACT 360 GGTGATATTG ATAAACAAAT AGAACTAGAA CAAGAAAAAA AGGAAGCAAA TAAGAGTGGG 420 ATAAAGTTAG AACAAGAAAG ACAGAAAACA GAACAAGAAA GACAGAAGAC AAATAAGAGT 480 GAGATAGAGT TAGAACAAGA AAGACAAAAA ACAAACAAGA GTGGGATAGA ACTCGCTAAT 540 AGTCAAATAA AAGCAGAACA AGAAAGACAA AAGACAGAAC AAGAAAAACA AAAAGCAAAT 600 AAGAGTGAGA TAGAGTTAGA ACAGCAAAAA CAAAAGACAA TTAATACACA AAGAGATTTG 660 ATTAAAGAAC AGAAAGATTT CATTAAAGAA ACAGAACAAA ATTGCCAAGA AAAACATGGC 720 CAATTGTTTA TTAAAAAAGC AAGAATTAAG ACCGGTATTA CTACTGGTAT TGCCATAGAA 780 ATAGAAGCTG AATGCAAAAC CCCTAAACCT GCAAAAACCA ATCAAACCCC TATCCAGCCA 840 AAACACCTCC CAAACTCTAA ACAACCCCGC TCTCAAAGAG GATCAAAAGC GCAAGAGCTT 900 ATCGCTTATT TGCAAAAAGA GCTAGAATCT CTGCCCTATT CGCAAAAAGC TATCGCTAAA 960 CAAGTGGATT TTTATAAACC AAGTTCTATC GCTTATTTAG AACTAGACCC TAGAGATTTT 1020 AAGGTTACAG AAGAATGGCA AAAAGAAAAT TTAAAAATAC GCTCTAAAGC TCAAGCTAAA 1080 ATGCTTGAAA TGAGAAACCC ACAAGCCCAC CTTCCAACCT CTCAAAGCCT TTTGTTCGTT 1140 CAAAAAATAT TTGCTGATAT TAATAAAGAA ATAGAAGCAG TTGCTAATAC TGAAAAGAAA 1200 ACAGAAAAAG CGGGTTATGG TTATAGTAAA AGGATGTAG 1239

(2) INFORMATION FOR SEQUENCE NO. 70:

(i) SEQUENCE CHARACTERISTICS:

200 (A) LENGTH: 450 base pairs (B) TYPE: nucleic acid (C) NUMBER OF FIBERS: two (D) TOPOLOGY: circular (ii) MOLECULA TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI- SENSE: NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix) SIGN: (A) NAME / KEY: different characters (B) PLACEMENT 1 ... 450

(xi) SEQUENCE DESCRIPTION: SEQ ID NO. 70:

TTGAATTGGG AGCATTTGAT GAAAAAATTA GCGTTTTCTT TATTATTTAC AGGGACTTTT TTGGGGCTTT TTTTGAATGC GAGTGATTTT AAGAGCATGG ATAACAAGCA ACTATTAGAG CAAGCAGGGA AAGTCGCTCC TAGCGAAGTT CCAGAGTTTC GCACAGAAGT CAATAAACGA TTAGAAGCGA TGAAAGAAGA AGAGCGTCAA AAATATAAAG CGGATTTTAA GAAAGCGATG GATAAGAATT TGGCTTCTTT AAGCCAAGAA GATCGCAACA AGCGTAAAAA AGAAATCCTT GAAGTCATTG CTAACAAAAA GAAAÄCAATG ACCATGAÄAG AGTATCGTGA AGAGGGGTTG GATTTGCATG ATTGCGCATG CGAAGGCCCT TTTCATGATC ATGAAAAAAA GGGGCAAAAA GGGAAAAAAC CAAGCCATCA TAAGCATTAG (2) INFORMATION SEQ ID NO. 71:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 615 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular (ii) MOLECULA TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE : NO (vi) ORIGINAL SOURCE:

120

180

240

300

360

420

450

201 (A) ORGANISM: Helicobacter pylori (ix)

(A) TITLE / KEY: different characters (B) LOCATION 1 ... 615 (xi) SEQUENCE DESCRIPTION: SEQ ID NO. 71:

ATGCAAGCAG TGATTTTAGC GAATGGGGAG TTTCCTAAAT CTAAAAAATG CTTAGACATT 60 TTACAAAACG CTCCCTTTTT AATCGCATGC GATGGGGCTG TTATATCATT GCATGCGCTT 120 CAATTCAAAC CCAGCGTTGT TATAGGCGAT TTGGATAGCA TTGATTCGCA TTTGAAAGCC 180 TTGTATAACC CTATACGCGT GAGCGAACAA GACAGCAACG ATTTGTCCAA AGCCTTTTTT 240 TATGCTTTGA ATAGGGGTTG TGATGATTTT ATTTTTTTAG GGTTGAATGG CAAGCGAGAA 300 GACCACGCTT TAGCGAACAC TTTTTTATTG TTGGAGTATT TTAAATTTTG CAAAAAAATC 360 CAATCCGTAA GCGATTATGG CCTTTTTAGG GTGTTAGAAA CCCCTTTTAC TTTGCCCAGT 420 TTTAAGGGGG AGCAAATCTC GCTTTTTAGC TTGGATCTTA AAGCCCGATT CACTTCTAAA 480 AACCTCAAAT ACCCCTTAAA AGACTTGCGT CTAÄAAACGC TCTTTTCCGG CTCGCTCAAT 540 GAAGCCACTA ATCATTGTTT TAGCCTTAGC TCTGAACCTA AATCGGTGGT GCTAGTGTAT 600 CAAAAATTCT catgut 615

(2) INFORMATION FOR SEQUENCE NO. 72:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 843 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular (ii) MOLECULA TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE : NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (Ix) SIGN: (A) NAME / KEY: different characters (B) PLACEMENT 1 ... 844 (Xi) DESCRIPTION 1 SEQUENCE: Sequence £. 72:

GTGTTTGACT CATTGGGCGG ATTTTTGGGG TATAAAACTT TTAAGCCGAT AGTGGATAAG 60

202

GTTAAAAATA TAAACGCTTG GATAAAAAAT TACGATAATA AAAAAGCTCA AGAGATTATG 120 GGTTTTATAG AAAATCCTAC GCCTGATTTC CAAAATAATA AGTTTTTGTG TGTTTTAAAC 180 CGACAAGGAA CAAGGCACAA CAATTATCTT GGTTTAACCT CTACAAACCT TCTAATCGGC 240 GCGATCTATT TCTCCATCCG CCATTGCATC AAAGCCACAT GGCAAAACGA TAGGGATCAA 300 TTCTACGCCC CTTATGATGA CGCTTTCCAA GACGACAGCG AGTTTAAAAA CAATTGTTTG 360 GCGTTCATGC TTTTTCACAC CCAAAACCGC ATCACTGCCA CTCAAGGGAC TAACCATTTT 420 ATCCCCTTTA GCGAAGATGA AGTTGATTCT AAAGAAAGGT ATTTGAGCCA TGCTTTATTA 480 GACTTTTTAA AAGGCGAAAT CAAAGAACCT AAAAAGAGCG ATAGCCTCTT TTTAAACGCC 540 AAAAAAGAAA ACAAGCCCCT AAAATTCAGC TCGAGCGCTT CAAAGGTGTT TGACGCTGGC 600 AGAGAGATTT ATCGCTATTA CCACACACAA GATTTCATCC ACACCCCCTA TAACGCTAAC 660 GCAAGCCTTT ATGACATCAA AGAATTTTTT CAAGGCCGTA ACAAGCAAGG CAGATTAAAC 720 TCACCCACCA AAGCCAAAGA TGAATATTAC AAACAGCTTT ACGCTAACTT GCAATACGCC 780 CTAAAAGATC TCGCCAAAGA AATACAGCCT AAAGTCTATG AATACGGATT TTTAAGGGAG 840 TAG 843

(2) INFORMATION FOR SEQUENCE NO. 73:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 930 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular (ii) MOLECULAR TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE : NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori

(ix) SIGN: (A) TITLE / KEY: Differently letters (B) LOCATION 1 ... 930

(xi) SEQUENCE DESCRIPTION: SEQ ID NO. 73:

TGTGACAGGG CAATTCCCCA TTGGCTTTTT AGTCTGGGAT ACCGCTACCC CCCCCCCTTA 60 AAACCAACCA ACGCGTTCAA TTTAGAAGTG TTTGACTCAT TGGGCGGATT TTTGGGGTAT 120 AAÄACTTTTA AGCCGATAGT GGATAAGGTT AAAAATATAA ACGCTTGGAT AAAAAATTAC 180 GATAATAAAA AAGCTCAAGA GATTATGGGT TTTATAGAAA ATCCTACGCC TGATTTCCAA 240 AATAATAAGT TTTTGTGTGT TTTAAACCGA CAAGGAACAA GGCACAACAA TTATCTTGGT 300 TTAACCTCTA CAAACCTTCT AATCGGCGCG ATCTATTTCT CCATCCGCCA TTGCATCAAA 360

203

GCCACATGGC AAAACGATAG GGATCAATTC TACGCCCCTT ATGATGACGC TTTCCAAGAC 420 GACAGCGAGT TTAAAAACAA TTGTTTGGCG TTCATGCTTT TTCACACCCA AAACCGCATC 480 ACTGCCACTC AAGGGACTAA CCATTTTATC CCCTTTAGCG AAGATGAAGT TGATTCTAAA 540 GAAAGGTATT TGAGCCATGC TTTATTAGAC TTTTTAAAAG GCGAAATCAA AGAACCTAAA 600 AAGAGCGATA GCCTCTTTTT AAACGCCAAA AAAGAAAACA AGCCCCTAAA ATTCAGCTCG 660 AGCGCTTCAA AGGTGTTTGA CGCTGGCAGA GAGATTTATC GCTATTACCA CACACAAGAT 720 TTCATCCACA CCCCCTATAA CGCTAACGCA AGCCTTTATG ACATCAAAGA ATTTTTTCAA 780 GGCCGTAACA AGCAAGGCAG ATTAAACTCA CCCACCAAAG CCAAAGATGA ATATTACAAA 840 CAGCTTTACG CTAACTTGCA ATACGCCCTA AAAGATCTCG CCAAAGAAAT ACAGCCTAAA 900 GTCTATGAAT ACGGATTTTT AAGGGAGTAAG 930 (2) 74:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 564 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular (ii) MOLECULA TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE : NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) NAME / KEY: various characters (B) LOCATION 1 ... 564 (xi) SEQUENCE DESCRIPTION: Sequence no. 74:

TTGGAAACTT ATATCATTGA TGCAGATAAT ATAGATGGGG ATTTATTTTT CTATAATCTT 60 ACTAGAAACA GCAATGATTT TTCCATGTTG CCCGTTTTTG AACTCGATCG CATTGCCCAA 120 AAAATTAGAA ATATTCTTAA AAAACATGGC AGTAGAAAAG ACATTATTTT AAAACACAAT 180 GAÄATTAAAG AAGCCTTTTT TAGCCCGTTC AAACCGCAGC TAAAAACCGT TCAAGTGTTC 240 CTCTCGCACT CGCATGCGGA TAAAAATAAG GCTTTAGGGG TTAAGGACTA TTTGGAAAGC 300 AAAACAAAAC GCAAAGTGTT TATCGATTCG CTTTTTTGGG ATTATAAAGA CGATGTTTTA 360 AACAAATTGG CAAAACACGA TGATATAAGC AAGATTGAAG ACGCTTTCAC GCTCATTCTC 420 AGAAAATCTT TACAAGATAT GATTGAAAAA TGCCCTTATT TTGTGTTTTT ACAAAGCAAG 480 AACAGCGTTT CTAATCAAGG GCTATCACGC ATCACTTATT CCGCATGGAT TTATGAAGAA 540 TTAAAAATCG CTTCATTCTA TTAG 564

204 (2) INFORMATION FOR SEQUENCE NO. 75:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 597 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular (ii) MOLECULAR TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE : NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix) SIGN: (A) NAME / KEY: different characters (B) PLACEMENT 1 ... 598

(xi) SEQUENCE DESCRIPTION: SEQ ID NO. 75:

TTGGAAACTT ATATCATTGA TGCAGATAAT ATAGATGGGG ATTTATTTTT CTATAATCTT ACTAGAAACA GCAATGATTT TTCCATGTTG CCCGTTTTTG AACTCGATCG CATTGCCCAA AAAATTAGAA ATATTCTTAA AAAACATGGC AGTAGAAAAG ACATTATTTT AAAACACAAT GAAATTAAAG AAGCCTTTTT TAGCCCGTTC AAACCGCAGC TAAAAACCGT TCAAGTGTTC CTCTCGCACT CGCATGCGGA TAAAAATAAG GCTTTAGGGG TTAAGGACTA TTTGGAAAGC AAAACAAAAC GCAAAGTGTT TATCGATTCG CTTTTTTGGG ATTATAAAGA CGATGTTTTA AACAAATTGG CAAAACACGA TGATATAAGC AAGATTGAAG ACGCTTTCAC GCTCATTCTC AGAAAATCTT TACAAGATAT GATTGÄAAAA TGCCCTTATT TTGTGTTTTT ACAAAGCAAG AACAGCGTTT CTAATCAAGG GCTATCACGC ATCACTTATT CCGCATGGAT TTATGAAGAA TTAAAAATCG CTTCATTTCT ATTAGCGCTA TTAACGAGAG TCGCCCAATT CCAATGA (2) INFORMATION FOR SEQUENCE NO. 76:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 570 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular

120

180

240

300

360

420

480

540

597 (ii) MOLECULA TYPE: DNA (genomic)

205 (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) NAME / KEY: various characters (B) LOCATION 1 ... 570 (xi) SEQUENCE DESCRIPTION: Sequence no. 76:

ATGATGACTA AGAACGCTTA TGCGTTTGTC GTGATTGAAA AAAGTATTAT GGTGTTTAAA 60

TGCGCCAAAG ACAAGGGGCT AATCCCTATC ACTGAAGGCT TTGTGCCGTT AAAAGAGGGC 120

TTTTTGAGAA GTTTTAAAGA GCGTTGCAAT CTGGATTTTT TAGAAAATTT AGACCTTTTG 180

TTTTTGTATG ACTACCAATT TCCAAGCGAG GTTTTTTCAT TGTGTAAGGA TTTGAAAAAT 240

TCCATTTGGG ACAGAAAGCT TGTGGTAGTG CTAGTGGAGG CTTTGGAGGG TTTTAAGGGT 300

TTGAATTTGT CTCTTAAGAT AGAAGATAGG CATTCTAATA GCTTGGGTAA TGGCGTTCAA 360

AAATTGCTCA CCAACGCTGA TTTGGGGAGC AACCACAAAC CAATCGTAAT AGACAGCATG 420

AAAACATACC ACCAAAGCCA GCAAGAAAAA TACAAAAGAG AAAGAGGCGA AACGCTAGAG 480

GTTCGCCCCA CAACACCCCC TAGCTATGGG GGTGGGAGCA TTAGAATCAG CGGCGATAAA 540 AAGCCTGATT CCAATGAAGA AAATTTTTAA 570 (2) INFORMATION FOR SEQUENCE NO. 77:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 1773 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular (ii) MOLECULA TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE : NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) TITLE / KEY: different characters

206 (B) LOCATION 1 ... 1773 (xi) SEQUENCE DESCRIPTION: SEQ ID NO. 77:

ATGAAAGCGA TAAAAATACT TCTTATAATG ACACTCAGTT TAAACGCTAT CAGCGTGAAT 60 AGGGCGTTGT TTGATTTAAA AGATTCGCAA TTAAAAGGGG AATTAACGCC AAAAATAGTG 120 GATTTTGGGG GTTATAAAAG CAACACCACA GAGTGGGGAG CTACGGCTTT AAACTATATC 180 AATGCGGCTA ATGGCGATGC GAAAAAATTC AGCGCGTTAG TGGAAAAAAT GCGTTTTAAC 240 TCTGGTATCT TGGGGAATTT TAGAGCGCAT GCACATTTGA GGCAAGCCCT AAÄATTGCAA 300 AAGAATTTGA AATATTGCCT TAAAATCATC GCTAGGGATT CTTTTTATAG TTACCGCACC 360 GGTATTTATA TCCCCTTAGG CATTTCTTTA AAAGATCAAA AAACGGCTCA AAAAATGCTC 420 GCTGATTTGA GCGTGGTAGG GGCGTATCTT AAAAAGCAAC AGGAGAATGA AAAGGCTCAA 480 AGCCCTTATT ACAGGAGCAA CAACTATTAC AACTCCTACT ATAGCCCTTA TTATGGCATG 540 TATGGCATGT ATGGAATGGG CATGTATGGA ATGTATGGCA TGGGCATGTA TGATTTTTAT 600 GACTTTTATG ATGGCATGTA TGGGTTCTAC CCTAACATGT TTTTCATGAT GCAAGTTCAA 660 GACTACTTGA TGTTAGAAAA TTACATGTAT GCACTCGATC AAGAAGAGAT TTTAGACCAT 720 GACGCTTCCA TCAACCAACT TGATACGCCT ACTGATGATG ACAGAGACGA TAAAGACGAT 780 AAATCTTCGC AACCAGCGAA TCTCATGAGC TTTTATCGTG ATCCCAAATT CAGCAAAGAC 840 ATTCAAACCA ACCGCTTGAA TAGCGCCTTA GTCAATTTAG ACAACAGCCA CATGCTCAAA 900 GACAATTCGC TCTTCCACAC TAAAGCCATG CCCACTAAAA GCGTGGATGC GATCACTTCT 960 CAAGCTAAAG AGCTTAACCA TTTGGTGGGG CAAATCAAAG AGATGAAGCA AGACGGGGCG 1020 AGTCCTAATA AGATTGATTC AGTGGTCAAT AAAGCTATGG AGGTTAGGGA CAAATTAGAC 1080 AACAACCTCA ACCAACTAGA CAATGACTTA AAAGATCAAA AAGGGCTTTC AAGCGAGCAG 1140 CAAGCCCAAG TGGATAAAGC CTTAGACAGC GTGCAACAAT TAAGCCATAG CAGCGATGTG 1200 GTAGGGAATT ATTTAGACGG GAGTTTGAAA ATTGATGGCG ATGACAGAGA CGATTTGAAT 1260 GATGCGATCA ATAACCCTAT GCAACAACCT GCGCAACAAA CGCCTATTAA CAACATGGAC 1320 AACACCCATG CAAATGACAG CAAAGATCAA GGGGGTAACG CGCTCATAAA CCCTAACAAC 1380 GCCACCAACG ATGATCACAA CGATGATCAC ATGGACACTA ACACCACTGA CACTAGCAAC 1440 GCAAACGACA CCCCCACTGA TGATAAAGAT GCTAGCGGCA ACAATACCGG CGATATGAAT 1500 AACACCGACA CCGGCAATAC GGACACTGGC AACACCGACA CCGGTAACAC TGATGATATG 1560 AGCAACATGA ACAACGGCAA CGATGATACG GGTAACACTA ACGACGACAT GGGTAATAGC 1620 AACGACATGG GCGATGACAT GAATAACGCG AACGACATGA ACGACGACAT GGGTAACAGC 1680 AACGATGACA ATGGGGGATA TGGGCGATAT TGGGTGGCGA GGGGGACATG TATGGGGAAT AACGATGACA TGA TGGGTGGCGA TATGGGAGAC 1740 1773

(2) INFORMATION FOR SEQUENCE NO. 78:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 588 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular (ii) MOLECULAR TYPE: DNA (genomic)

207 (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) NAME / KEY: various characters (B) LOCATION 1 ... 588 (xi) SEQUENCE DESCRIPTION: Sequence no. 78:

TTGAATTTAC GATTGGCTGG AGCAAGCGTT TTAACGGCTT GTGTCTTTTC GGGGTGTTTT 60

TTTTTAAAAA TGTTTGACAA AAAACTTTCT AGCAACGATT GGCATATCCA AAAAGTAGAA 120

ATGAACCATC AAGTGTATGA CATTGAAACC ATGCTCGCTG ATAGCGCTTT TAGAGAGCAT 180

GAAGAAGAGC AAGACTCCTC TTTAAATACC GCTTTGCCTG AAGATAAAAC AGCGATTGAA 240

GCCAAAGAGC AAGAGCAAAA AGAAAAAAGG AAACACTGGT ATGAGCTTTT TAAAAAGAAG 300

CCAAAGCCCA AAAGCTCTAT GGGAGAGTTT GTGTTTGATC AAAAAGAAAA TCGTATTTAT 360

GGGAAAGGCT ATTGCAACCG GTATTTTGCT AGCTACACAT GGCAGGGCGA TAGGCACATC 420

GCAATTGAAG ATAGCGGGAT TTCAAGAAAA GTGTGTAGAG ATGAGCATTT GATGGCGTTT 480

GAATTGGAAT TTATGGAGAA TTTTAAGGGT AATTTTGCGG TAACTAAGGG CAAGGACACG 540

CTCATTTTAG ACAACCAAAA AATGAAAATT TATTTGAAAA CGCCATGA 588 (2) INFORMATION FOR SEQUENCE NO. 79:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 2235 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular (ii) MOLECULA TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE : NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) TITLE / KEY: different characters

208 (B) LOCATION 1 ... 2235 (xi) SEQUENCE DESCRIPTION: SEQ ID NO. 79:

ATGTTAAAAC TCGCCAGTAA AACGATTTGT TTGTCCCTAA TCAGCTCATT CACGGCTGTA 60 GAAGCCTTTC AAAAACACCA AAAAGACGGC TTTTTCATAG AAGCCGGCTT TGAAACCGGG 120 CTATTACAAG GCACACAAAC CCAAGAACAA ACCATAGCCA CCACTCAAGA AAAACCCAAA 180 CCCAAACCCA AACCAAAACC CATTACCCCT CAAAGCACCT ATGGGAAATA CTACATCTCC 240 CAAAGCACCA TTTTAAAGAA TGCGACTGAG TTGTTTGCAG AGGATAATAT CACCAACTTA 300 ACCTTTTACT CTCAAAACCC TGTGTATGTA ACCGCTTATA ACCAAGAAAG CGCTGAAGAA 360 GCTGGCTATG GTAATAACAG CTTGATTATG ATACAAAACT TCTTGCCTTA TAACTTGAAC 420 AACATTGAGC TGAGTTACAC GGACGATCAA GGCAATGTGG TCAGTTTGGG CGTGATAGAG 480 ACTATCCCTA AACAATCTCA AATCATTCTG CCCGCAAGCT TGTTTAACGA CCCACAGCTT 540 AACGCCGATG GCTTCCAACA ACTCCAAACC AACACCACAC GATTTTCTGA TGCCAGCACG 600 CAGAATCTGT TTAACAAGCT CAGCAAGGTT ACAACCAATC TTCAAATGAC TTATATCAAT 660 TACAACCAAT TTTCTAGCGG TAACGGCAGT GGCTCTAAAC CCCCATGCCC CCCATACGAA 720 AACCAAGCAA ATTGTGTGGC TAAAGTGCCG CCTTTCACCT CTCAAGACGC TAAAAATTTG 780 ACCAATTTAA TGCTGAACAT GATGGCGGTG TTTGATTCTA AATCTTGGGA AGACGCCGTC 840 TTAAACGCTC CTTTCCAATT CAGCGACAAC AACCTGTCAG CGCCATGTTA TTCTGATTAC 900 CTTACATGCG TGAATCCTTA CAACGATGGG CTTGTTGATC CTAAATTGAT CGCCAAAAAT 960 AAAGGAGATG AATACAATAT AGAAAACGGG CAAACAGGCT CAGTGATATT AACGCCGCAA 1020 GATGTTATCT ATAGCTATAG AGTCGCTAAT AATATTTATG TGAATCTCTT GCCCACAAGA 1080 GGAGGGGATT TAGGGTTAGG GTCTCAATAT GGTGGCCCGA ATGGCCCAGG CGATGATGGC 1140 ACCAATTTTG GCGCTTTAGG GATATTGTCC CCTTTCTTAG ACCCTGAAAT ATTGTTTGGC 1200 AAAGAATTGA ATAAAGTCGC CATCATGCAA TTAAGAGACA TCATCCATGA ATACGGCCAT 1260 ACTTTAGGCT ATACGCATAA CGGGAACATG ACTTATCAAA GAGTGCGCAT GTGCGAAGAA 1320 AACAATGGGC CAGAAGAGCG CTGTCAGGGC GGAAGGATAG AGCAAGTGGA TGGGAAAGAA 1380 GTGCAAGTGT TTGACAACGG GCATGAAGTG CGAGACACCG ATGGCTCTAC CTATGATGTG 1440 TGTTCTCGTT TTAAAGATAA GCCCTATACA GCGGGCAGCT ATCCTAATTC CATCTATACC 1500 GATTGCTCTC AAGTCCCCGC TGGGCTTATA GGCGTTACCA GCGCTGTTTG GCÄACAACTC 1560 ATTGATCAAA ACGCCCTACC GGTGGATTTT ACTAATTTGA GCAGCCAAAC CAACTATTTG 1620 AACGCCAGCT TGAACACGCA AGACTTTGCG ACCACCATGC TTAGCGCGAT CAGTCAAAGC 1680 CTTTCATCTT CTAAATCTAG CGCCACTACT TATCGCACTT CAAAAACCTC ACGGCCCTTT 1740 GGAGCCCCCC TATTAGGCGT TAATCTTAAA ATGGGCTATC AAAAATATTT TAATGATTAT 1800 CTAGGGTTGT CTTCTTATGG CATTATCAAA TACAACTACG CTCAAGCCAA CAACGAAAAA 1860 ATCCAGCAAT TAAGCTATGG CGTGGGAATG GATGTGCTGT TTGATTTCAT CACCAATTAC 1920 ACTAACGAAA AGAACCCCAA AAGCAATCTA ACCAAGAAAG TTTTCACTTC CTCTCTTGGG 1980 GTGTTTGGGG GGTTAAGGGG CTTATACAAC AGCTATTATT TGTTGAACCA ATACAAAGGG 2040 AGCGGTAATT TAAATGTGAC CGGTGGGTTG AATTACCGCT ACAAGCATTC CAAATATTCT 2100 ATAGGCATTA GCGTTCCTTT GGTCCAGTTG AAATCTAGGA TCGTTTCTAG CGATGGTGCT 2160 TATACCAATT GGGTGGATTT CTATCACCCT TCTAA CAATGAAGGG GGCAGTCATT TTAAAGTGTT TTTTAATTAC 2220 2235

(2) INFORMATION FOR SEQUENCE NO. 80

209 (i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 1590 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular (ii) MOLECULA TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE : NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) NAME / KEY: various characters (B) LOCATION 1 ... 1590 (xi) SEQUENCE DESCRIPTION: Sequence £. 80:

ATGACTTATA TCAATTACAA CCAATTTTCT TGCCCCCCAT ACGAAAACCA AGCAAATTGT GACGCTAAAA ATTTGACCAA TTTAATGCTG TGGGAAGACG CCGTCTTAAA CGCTCCTTTC TGTTATTCTG ATTACCTTAC ATGCGTGAAT TTGATCGCCA ÄAAATAAAGG AGATGAATAC ATATTAACGC CGCAAGATGT TATCTATAGC CTCTTGCCCA CAAGAGGAGG GGATTTAGGG CCAGGCGATG ATGGCACCAA TTTTGGCGCT GAAATATTGT TTGGCAAÄGA ATTGAATAAA CATGAATACG GCCATACTTT AGGCTATACG CGCATGTGCG AAGAAAACAA TGGGCCAGAA GTGGATGGGA AAGAAGTGCA AGTGTTTGAC TCTACCTATG ATGTGTGTTC TCGTTTTAAA AATTCCATCT ATACCGATTG CTCTCAAGTC GTTTGGCAAC AACTCATTGA TCAAAACGCC CAAACCAACT ATTTGAACGC CAGCTTGAAC GCGATCAGTC AAAGCCTTTC ATCTTCTAAA ACCTCACGGC CCCTCTATTA TATTTTAATG ATTATCTAGG GTTGTCTTCT GCCAACAACG AAAAAATCCA GCAATTAAGC TTCATCACCA ATTACATA

AGCGGTAACG GCAGTGGCTC TAAACCCCCA GTGGCTAAAG TGCCGCCTTT CACCTCTCAA AACATGATGG CGGTGTTTGA TTCTAAATCT CAATTCAGCG ACAACAACCT GTCAGCGCCA CCTTACAACG ATGGGCTTGT TGATCCTAAA AATATAGAAA ACGGGCAAAC AGGCTCAGTG TATAGAGTCG CTAATAATAT TTATGTGAAT TTAGGGTCTC AATATGGTGG CCCGAATGGC TTAGGGATAT TGTCCCCTTT CTTAGACCCT GTCGCCATCA TGCAATTAAG AGACATCATC CATAACGGGA ACATGACTTA TCAAAGAGTG GAGCGCTGTC AGGGCGGAAG GATAGAGCAA AACGGGCATG AAGTGCGAGA CACCGATGGC GATAAGCCCT ATACAGCGGG CAGCTATCCT CCCGCTGGGC TTATAGGCGT TACCAGCGCT CTACCGGTGG ATTTTACTAA TTTGAGCAGC ACGCAAGACT TTGCGACCAC CATGCTTAGC TCTAGCGCCA CTACTTATCG CACTTCAAAA GGCGTTAATC TTAAAATGGG CTATCAAAAA TATGGCATTA TCAAATACAA CTACGCTCAA TATGGCGTGG GAATGGATGT

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540

600

660

720

780

840

900

960

1020

1080

1140

1200

1260

1320

210

ACTTCCTCTC TTGGGGTGTT AACCAATACA AAGGGAGCGG CATTCCAAAT ATTCTATAGG TCTAGCGATG GTGCTTATAC GTGTTTTTTA

TGGGGGGTTA AGGGGCTTAT TAATTTAAAT GTGACCGGTG CATTAGCGTT CCTTTGGTCC CAATTCTATC ACCCTCAATG GATTTTCTA

ACAACAGCTA TTATTTGTTG GGTTGAATTA CCGCTACAAG AGTTGAAATC TAGGATCGTT AAGGGGGCAG TCATTTTAAA

1380

1440

1500

1560

1590 (2) INFORMATION FOR SEQUENCE NO. 81:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 564 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular (ii) MOLECULA TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE : NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) NAME / KEY: various characters (B) LOCATION 1 ... 564 (xi) SEQUENCE DESCRIPTION: Sequence £. 81:

TTGGGTTGCG TATCAATGAC TCTAGGTATT GATGAAGCGG GGAGGGGGTG TTTGGCCGGT TCGCTTTTTG TGGCGGGGGT GGTGTGTAAT GAAAAAATAG CCTTAGAATT TCTAAAAATG GGTCTTAAGG ATAGCAAGAA GCTCAGCCCC AAAAAGCGCT TTTTCTTAGA AGATAAAATC AAAACGCATG GTGAGGTGGG GTTTTTCGTG GTTAAAAAAA GCGCGAATGA AATTGATCAT TTGGGCTTAG GGGCGTGTTT GAAACTCGCT ATTGAAGAAA TTGTAGAAAA TGGTTGCTCT TTAGCCAATG AAATAAAAAT AGATGGCAAC ACGGCGTTTG GCTTGAACAA ACGCTACCCC AACATACAAA CCATCATCAA GGGCGATGAA ACAATCGCTC AAATCGCTAT GGCGTCTGTT TTGGCGAAAG CTTCTAAGGA TAGGGAAATG TTAGAACTGC ACGCTTTGTT TAAGGAATAC GGCTGGGATA AGAATTGCGG GTATGGGACT AAACAACATA TAGAAGCGAT CAATAAGCTA GGGGCTACGC TTTCATCGGC ATAG

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420

480

540

564 (2) INFORMATION FOR SEQUENCE NO. 82:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 615 base pairs

211 (B) TYPE: nucleic acid (C) NUMBER OF FIBERS: two (D) TOPOLOGY: circular (ii) MOLECULAR TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE :

(A) ORGANISM: Helicobacter pylori (ix)

(A) NAME / KEY: various characters (B) LOCATION 1 ... 615 (xi) SEQUENCE DESCRIPTION: Sequence no. 82:

ATGACTCTAG GTATTGATGA AGCGGGGAGG GGGTGTTTGG CCGGTTCGCT TTTTGTGGCG 60

GGGGTGGTGT GTAATGAAAA AATAGCCTTA GÄATTTCTAA AAATGGGTCT TAAGGATAGC 120

AAGAAGCTCA GCCCCAAAAA GCGCTTTTTC TTAGAAGATA AAATCAAAAC GCATGGTGAG 180

GTGGGGTTTT TCGTGGTTAA AAAAAGCGCG AATGAAATTG ATCATTTGGG CTTAGGGGCG 240

TGTTTGAAAC TCGCTATTGA AGAAATTGTA GAAAATGGTT GCTCTTTAGC CAATGAAATA 300

AAAATAGATG GCAACACGGC GTTTGGCTTG AACAAACGCT ACCCCAACAT ACAAACCATC 360

ATCAAGGGCG ATGAAACAAT CGCTCAAATC GCTATGGCGT CTGTTTTGGC GAAAGCTTCT 420

AAGGATAGGG AAATGTTAGA ACTGCACGCT TTGTTTAAGG AATACGGCTG GGATAAGAAT 480

TGCGGGTATG GGACTAAACA ACATATAGAA GCGATCAATA AGCTAGGGGC TACGCCTTTT 540

CATCGGCATA GCTTCACGCT TAAAAACCGC ATCTTAAATC CCAAACTCTT AGAGGTGGAA 600 CAACGCCTTG TTTAA 615 (2) INFORMATION FOR SEQUENCE NO. 83:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 579 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular (ii) MOLECULAR TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE : NOT

212 (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (Ix) SIGN: (A) NAME / KEY: different characters (B) PLACEMENT 1 ... 578 (Xi) DESCRIPTION i SEQUENCES: Sequence £. 83:

ATGAATGCAT TGAAAAAATT AAGTTTTTGC GCCTTGTTAT CCCTAGGCCT CTTCGCTCAA ACAGTGCATG CTCAGCATTT AAAGGACACG ATTAACTATC CTGATTGGCT TAAAATCAAT CTTTTTGATA AAAAGAACCC GCCCAATCAA TATGTCGGAT CGGCTTCAAT TTCTGGTAAA AGGAACGATT TTTATTCCAA TTACATCCCC TATGATGACA AATTGCCCCC TGAAAAGAAC GCTGAAGAAA TCGCTCTTTT AAGGGCCAGA ATGAACGCTT ACAGCACTTT AGAAAGCGCT TTACTCACTA AAATGTGCAA TCGCATTGTT AAAGCGCTTC AAGTTAAAAA TAATGTTATC AGCCATTTAT TCGGGTTTGT TGATTTTTTA ACGTCTAAAT CCATTTTGGC TAAAAGGTTC GTGGATACCA CCAACCATCG TGTGTATGTC ATGGTGCAAT TCCCTTTCAT TCAGCCTGAA GACTTAATCG CTTACTTTAA AGCCAAACGC ATCGACCTTT CTTTAGCGAG CGCTACCAAT CTCAGCGCCA TTTTAAACAA GGCGTTGTTC CACCTCTAA (2) INFORMATION FOR SEQUENCE C. 84:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 261 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular (ii) MOLECULAR TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE : NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) TITLE / KEY: various characters (B) LOCATION 1 ... 261

120

180

240

300

360

420

480

540

579 (xi) SEQUENCE DESCRIPTION: Sequence £. 84:

213

ATGAATGCAT TGAAAAAATT AAGTTTTTGC GCCTTGTTAT CCCTAGGCCT CTTCGCTCAA 60 ACAGTGCATG CTCAGCATTT AAAGGACACG ATTAACTATC CTGATTGGCT TAAAATCAAT 120 _CTTTTTGATA AAAAGAACCC GCCCAATCAA TATGTCGGAT CGGCTTCAAT TTCTGGTAAA 180 AGGAACGATT TTTATTCCAA TTACATCCCC TATGATGACA AATTGCCCCC TGAAAGAACG CTGAAGAAAT CGCTCTTTTA 240 and 261 (2) INFORMATION FOR SEQ ID NO. 85:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 228 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular (ii) MOLECULA TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE : NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) NAME / KEY: various characters (B) LOCATION 1 ... 228 (xi) SEQUENCE DESCRIPTION: Sequence £. 85:

TTGAAAATTT TAACCCTTTT TTTGATAGGT TTAAACGCAT TGTTCGCCCT AGATTTGAAC 60 GCGCTTAAAA CAGAAATCAA AGAAACCTAT CTCAAAGAAT ACAAAGACTT AAAATTGGAA 120 ATTGAAACAA TTAATTTAGA AATCCCAGAG CGTTTTTCTC ACGCTTCCAT TTTAAGCTAT 180 GAATTGAACG CTTCTAACAA GCTTAAAAAA GATGGGTCGT GTTTTTAA 228 (2) INFORMATION FOR SEQ ID NO. 86:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 636 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular (ii) MOLECULA TYPE: DNA (genomic)

214 (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) NAME / KEY: different characters (B) LOCATION 1 ... 636 (xi) SEQUENCE DESCRIPTION: Sequence £. 86:

ATGTTTTCAA TAATTCTGGG GGGGGGGGGG GGTAATACCC CATGCGGCTT GACATGGCAA 60

CACTTCAAAT TAGGGGATTT GTTTGAAATT GAAAAAACCT TAAGCTTTAA TAAAGACGCT 120

TTAACGCAAG GACAAGATTA CGATTATATT ACAAGAACTT CGCAAAATCA AGGCGTTTTG 180

CAAACTACAG GATTTGTCAA TGCAGAAAAT TTAAACCCAC CATTTACTTG GAGTTTAGGG 240

CTTTTGCAAA TGGATTTTTT CTATCGTAAA ÄAGTCATGGT ATGCGGGACA ATTCATGCGA 300

AAAATCACAC CAAAAACTGA AATTAAAAAT AAAATTAATT CACGCATAGC CCACTATTTC 360

ACAACGCTTT TAAACGCCTT AAAACGCCCT TTATTGAGTG TATTAGTTAG GGATATTGAT 420

AAAACTTTTA GGGAGCAAAA AATCCAACTA CCCCTAAAAC CCACCGCTAA AACTCAAAGC 480

CTTGATGGTA TTGATTTTGA TTTCATGCAC ACCCTAATCA ACGCCCTGAT GAAGCAAACC 540

ATTCAAGGCG TGGTTCAATA CTGCGACGCT AAAATACAGG CTACAAAAGA AGTTATCAGC 600

CAAGAAACGC CTATTCAAAA AGACTCGTTA TTTTGA 636 (2) INFORMATION FOR SEQUENCE NO. 87:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 1221 base pairs (B, TYPE: nucleic acid (C) FIBER NUMBER: two (D, TOPOLOGY: circular (ii) MOLECULAR TYPE: DNA (genomic, (iii, HYPOTHETICAL: NO (iv, ANTI-SENSE) : NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) TITLE / KEY: different characters

215 (B) LOCATIONS 1 ... 1221 (xi) SEQUENCE DESCRIPTION: SEQ ID NO. 87:

GTGATTGGCC CCCTTAGCAG CCAACTCAAC GCTATTAAGT GGGGCGAGTT CAAATTAGGG 60 GATTTGTTTG AAGCGAGTAA CGGCGATTTT GACATTCAAA AACGCCACAT CAATCATAAG 120 GGCGAATTTG TCATCACCGC AGGGCTTAGC AATAATGGCG TTTTAGGGCA AAGCGATATA 180 AAAGCAAAAG TTTTTGAAAG CCATACCATT ACTATTGACA TGTTTGGTTG CGCGTTTTAT 240 CGCAGTTTTG CTTATAAAAT GGTAACACAT GCTAGGGTAT TTTCTCTCAA ACCTAAATTT 300 GAAATCAACC ATAAAATCGG CTTGTTTTTA TCCACGCTAT TTTTTGGTTA CCATAAAAAA 360 TTCGGCTATG AAAACATGTG TTCATGGGCA AAAATTAAAA ACGATAAAGT CATTCTACCC 420 CTAAAACCCA CCGCTAACAC TCAAACCCTT GAGGGTATTG ATTTTGATTT CATGGAAAAA 480 TTCATAGCCG AACTTGAGCA GTGTCGGCTC GCCGAACTTC AGGCTTATTT AAAAGCTACA 540 GGGCTAGAAA ACACCACCCT TTCTAACGAT GAAGAAAATG CCCTTAATGT TTTCAATAAT 600 TCTGGGGGGG GGGGGGGTAA TACCCCATGC GGCTTGACAT GGCAACACTT CAAATTAGGG 660 GATTTGTTTG AAATTGAAAA AACCTTAAGC TTTAATAAAG ACGCTTTAAC GCAAGGACAA 720 GATTACGATT ATATTACAAG AACTTCGCAA AATCAAGGCG TTTTGCAAAC TACAGGATTT 780 GTCAATGCAG AAAATTTAAA CCCACCATTT ACTTGGAGTT TAGGGCTTTT GCAAATGGAT 840 TTTTTCTATC GTAAAAAGTC ATGGTATGCG GGACAATTCA TGCGAAAAAT CACACCAAAA 900 ACTGAAATTA AAAATAAAAT TAATTCACGC ATAGCCCACT ATTTCACAAC GCTTTTAAAC 960 GCCTTAAAAC GCCCTTTATT GAGTGTATTA GTTAGGGATA TTGATAAAAC TTTTAGGGAG 1020 CAAAAAATCC AACTACCCCT AAAACCCACC GCTAAAACTC AAAGCCTTGA TGGTATTGAT 1080 TTTGATTTCA TGCACACCCT AATCAACGCC CTGATGAAGC AAACCATTCA AGGCGTGGTT 1140 CAATACTGCG ACGCTAAAAT ACAGGCTACA AAAGAAGTTA TCAGCCAAGA AACGCCTATT 1200 CAAAAAGACT CGTTATTTTG A 1221

(2) INFORMATION FOR SEQUENCE NO. 88:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 828 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular (ii) MOLECULA TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE : NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

216 (A) NAME / KEY: miscellaneous characters (B) LOCATION 1 ... 828 (xi) SEQUENCE DESCRIPTION: Sequence no. 88:

ATGAGTAAGA GTTTATACCA AACTTTAAAC GTGAGCGAAA ACGCCAGCCA AGATGAAATC 60 AAAAAATCCT ACCGCCGTTT AGCCAGGCAA TACCACCCGG ATTTGAATAA AACCAAAGAA 120 GCCGAAGAGA AATTCAAAGA AATCAACGCC GCTTATGAAA TTTTGAGCGA TGAAGAAAAA 180 CGCCGCCAAT ACGATCAATT TGGCGACAAC ATGTTTGGCG GGCAGAATTT CAGCGATTTT 240 GCCAGAAGCC GTGGTCCTAG TGAAGATTTA GATGATATTT TAAGCTCTAT TTTTGGGAAA 300 GGAGGCTTTT CGCAAAGATT TTCTCAAAAT TCGCAAGGCT TTTCTGGCTT TAATTTTTCC 360 AATTTCGCCC CTGAAAATTT AGATGTAACC GCTATTTTAA ATGTCTCTGT TTTAGACACC 420 CTTTTAGGCA ATAAAAAACA AGTGAGCGTC AATAATGAGA CTTTTAGCCT TAAAATCCCT 480 ATCGGCGTGG AAGAGGGCGA AAAGATTAGG GTTCGCAACA AAGGGAAAAT GGGGCGAACG 540 GGTAGGGGCG ATTTGCTCTT ACAGATCCAT ATTGAAGAAG ATGAAATGTA TAGGCGCGAA 600 AAAGACGATA TTATCCAAAT CTTTGATTTA CCCTTAAAAA CGGCTCTTTT TGGAGGGAAA 660 ATTGAAATCG CTACTTGGCA TAAAACCTTA ACCCTAACCA TTCCCCCTAA CACCAAAGCC 720 ATGCAAAAAT TCCGCATCAA AGACAAAGGG ATCAAÄAGCA GAAAAACTTC GCATGTGGGG 780 GATTGTATTG CAAGCTCGTT TGATCTGCTA AAATTGAAAC GCTTCTAA 828

(2) INFORMATION FOR SEQUENCE NO. 89:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 837 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular (ii) MOLECULA TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE : NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) NAME / KEY: various characters (B) LOCATION 1 ... 837 (xi) SEQUENCE DESCRIPTION: Sequence no. 89:

ATGAGTAAGA GTTTATACCA AACTTTAAAC GTGAGCGAAA ACGCCAGCCA AGATGAAATC 60

217

AAAAAATCCT ACCGCCGTTT AGCCAGGCAA TACCACCCGG ATTTGAATAA AACCAAAGAA GCCGAAGAGA AATTCAAAGA AATCAACGCC GCTTATGAAA TTTTGAGCGA TGAAGAAAAA CGCCGCCAAT ACGATCAATT TGGCGACAAC ATGTTTGGCG GGCAGAATTT CAGCGATTTT GCCAGAAGCC GTGGTCCTAG TGAAGATTTA GATGATATTT TAAGCTCTAT TTTTGGGAAA GGAGGCTTTT CGCAAAGATT TTCTCAAAAT TCGCAAGGCT TTTCTGGCTT TAATTTTTCC AATTTCGCCC CTGAAAATTT AGATGTAACC GCTATTTTAA ATGTCTCTGT TTTAGACACC CTTTTAGGCA ATAAAAAACA AGTGAGCGTC AATAATGAGA CTTTTAGCCT TAAAATCCCT ATCGGCGTGG AAGAGGGCGA AAAGATTAGG GTTCGCAACA AAGGGAAAAT GGGGCGAACG GGTAGGGGCG ATTTGCTCTT ACAGATCCAT ATTGAAGAAG ATGAAATGTA TAGGCGCGAA AAAGACGATA TTATCCAAAT CTTTGATTTA CCCTTAAAAA CGGCTCTTTT TGGAGGGAAA ATTGAAATCG CTACTTGGCA TAAAACCTTA ACCCTAACCA TTCCCCCTAA CACCAAAGCC ATGCAAAAAT TCCGCATCAA AGACAAAGGG ATCAAAAGCA GAAAAACTTC GCATGTGGGG GATTGTATTG CAAGCTCGTT TGATCTGCCT AAAATTGAAA CGCTTCTAAT GAGTTGA (2) INFORMATION FOR SEQ ID NO. 90:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 699 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular (ii) MOLECULA TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE : NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) NAME / KEY: various characters (B) LOCATION 1 ... 699 (xi) SEQUENCE DESCRIPTION: Sequence no. 90:

GTGGTTCAAA AATTTAATTT TTATAAGACA GGTGGCATGC GTTTAAAACA TTTTAAGACA TTCCTTTTTA TCACAATGGC GGTGATTGTG ATAGGCACTG GTTGTGCGAA TAAAAAGAAA AAAAAAGATG AATACAACAA ACCGGCGATC TTTTGGTATC AAGGGATTTT GAGAGAAATT CTTTTTGCTA ATTTAGAAAC AGCGGACAAT TACTATTCTT CCTTACAGAG CGAACACATC AATTCCCCCC TTGTCCCAGA AGCTATGCTA GCTTTAGGGC AAGCGCACAT GAAAAAGAAA GAGTATGTTT TAGCGTCTTT TTACTTTGAT GAATACATCA AGCGCTTTGG GACGAAGGAC AATGTGGATT ATTTGACCTT TTTGAAACTG CAATCGCATT ATTACGCTTT CAAAAACCAT

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360

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480

540

600

660

720

780

837

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360

420

218

TCTAAAGACC AGGAATTTAT CTCTAATTCT ATTGTGAGTT TAGGCGAATT TATAGAAAAA 480 TACCCTAACA GCCGTTACCG CCCCTATGTA GAATACATGC AAATCAAATT CATTTTAGGG 540 CAAAATGAGC TCAATCGCGC GATCGCGAAT GTCTATAAAA AACGCCACAA GCCCGAGGGC 600 GTGAAACGCT ATTTAGAAAG GATAGATGAG ACTTTAGAAA AAGAGACTAA ACCCAAACCA 660 TCGCACATGC CTTGGTATGT GTTAATTTTT GATTGGTAG 699 (2) INFORMATION FOR SEQ ID NO. 91:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 345 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular (ii) MOLECULA TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE : NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) NAME / KEY: various characters (B) LOCATION 1 ... 345 (xi) SEQUENCE DESCRIPTION: Sequence no. 91:

ATGCGTTTTT TGAATAACAA ACATAGAGAA AAGGGCTTAA AGGCTGAAGA AGAAGCTTGC 60 GGGTTTTTAA AAACGCTGGG TTTTGAAATG ATAGAGAGGA ACTTTTTTTC ACAATTTGGT 120 GAAATTGATA TTATCGCTTT GAAAAAAGGG GTTTTGCATT TCATTGAAGT CAAAAGCGGG 180 GAAAATTTTG ATCCCATTTA TGCGATCACG CCGAGCAAAT TAAAAAAGAT GATTAAAACG 240 ATCCGCTGTT ATTTGTCTCA AAAAGATCCC AATAGCGATT TTTGCATTGA CGCTCTTATT 300 GTGAAAAATG GTAAATTTGA GCTTTTAGAA AATATCACTT TTTAG 345 (2) INFORMATION FOR SEQ ID NO. 92:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 306 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular

219 (ii) MOLECULA TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) NAME / KEY: various characters (B) LOCATION 1 ... 306 (xi) SEQUENCE DESCRIPTION: Sequence no. 92:

ATGGGCAGCA TTGGGGCTAT GACTAAAGGG AGCTCTGATA GGTATTTTCA AGAGGGCGTG GCGAGTGAAA AATTAGTCCC AGAAGGCATT GAGGGGCGTG TGCCTTATCG TGGTAAGGTT TCGGATATGA TTTTCCAATT AGTAGGGGGC GTGCGTTCTT CTATGGGGTA TCAGGGGGCG AAGAATATTT TGGAATTGTA TCAAAACGCT GAATTTGTAG AAATCACTAG CGCGGGGTTA AAAAAAAGCC ATGTGCATGG CGTGGATATT ACTAAAGAAG CCCCTAATAT TATGGGTGAA TTTTAA (2) INFORMATION FOR SEQ ID NO. 93:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 1446 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular (ii) MOLECULA TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE : NOT

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240

300

306 (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix) SIGN: (A) NAME / KEY: different characters (B) PLACEMENT 1. . . 1446

(xi) SEQUENCE DESCRIPTION: SEQ ID NO. 93:

220

ATGAGAATTT TACAAAGGGC TTTGACTTTT GAAGACGTGT TGATGGTGCC TAGAAAATCC 60 AGCGTTTTAC CTAAAGATGT GAGCTTAAAG TCTCGCCTAA CCAAAAACAT TGGTTTGAAT 120 ATCCCTTTTA TTAGTGCGGC TATGGATACG GTTACAGAGC ATAAAACCGC TATCGCTATG 180 GCGCGCCTTG GGGGTATTGG CATCGTGCAT AAAAACATGG ATATTCAAAC GCAAGTCAAA 240 GAAATCACTA AAGTTAAAAA AAGCGAGAGC GGGGTGATTA ATGATCCTAT TTTTATCCAT 300 GCGCACAGGA CGCTAGCGGA CGCTAAAGTC ATAACGGATA ATTATAAGAT TTCAGGCGTG 360 CCTGTGGTAG ATGATAAGGG GTTGTTGATT GGGATTTTAA CCAACAGAGA CGTGCGTTTT 420 GAAACCGATT TGAGTAAAAA AGTGGGCGAT GTGATGACTA ÄAATGCCTTT AGTTACCGCT 480 CATGTGGGCA TTAGCTTAGA TGAAGCGAGC GATTTGATGC ACAAGCATAA GATTGAAAAA 540 TTGCCCATTG TGGATAAAGA TAATGTTTTA AAAGGCTTGA TCACGATCAA AGACATTCAA 600 AAACGCATTG AATACCCTGA GGCCAATAAA GATGATTTTG GGAGGTTGAG AGTGGGGGCG 660 GCTATTGGAG TGGGGCAGTT GGATAGGGCT GAAATGTTAG TTAAAGCGGG GGTGGATGCG 720 TTGGTGTTAG ACAGCGCGCA TGGGCATTCA GCCAATATTT TACACACTTT AGAAGAGATT 780 AAAAAAAGCT TGGTAGTGGA TGTGATTGTG GGGAATGTGG TTACTAAAGA AGCCACAAGC 840 GATTTGATTA GCGCGGGAGC GGACGCTGTT AAAGTGGGTA TTGGGCCAGG AAGCATTTGC 900 ACCACTAGGA TTGTGGCCGG GGTGGGAATG CCCCAAGTGA GCGCAATTGA TAATTGCGTG 960 GAAGTGGCGT CTAAATTTGA TATTCCTGTG ATTGCCGATG GAGGGATCCG CTATTCAGGC 1020 GATGTGGCTA AGGCTCTAGC TTTAGGAGCA TCAAGCGTGA TGATAGGCTC TTTACTCGCT 1080 GGCACAGAAG AATCTCCAGG GGATTTTATG ATTTACCAAG GGAGGCAATA TAAAAGCTAT 1140 AGGGGCATGG GCAGCATTGG GGCTATGACT AAAGGGAGCT CTGATAGGTA TTTTCAAGAG 1200 GGCGTGGCGA GTGAAAAATT AGTCCCAGAA GGCATTGAGG GGCGTGTGCC TTATCGTGGT 1260 AAGGTTTCGG ATATGATTTT CCAATTAGTA GGGGGCGTGC GTTCTTCTAT GGGGTATCAG 1320 GGGGCGAAGA ATATTTTGGA ATTGTATCAA AACGCTGAAT TTGTAGAAAT CACTAGCGCG 1380 GGGTTAAAAG AAAGCCATGT GCATGGCGTG GATATTACTA AAGAAGCCCC TAATTATTAT 1440 GGGTGA 1446

(2) INFORMATION FOR SEQUENCE NO. 94:

(i) SEQUENCE CHARACTERISTICS:

(Ά) LENGTH: 615 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular (ii) MOLECULA TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE : NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori

221 (ix) SIGN:

(A) NAME / KEY: various characters (B) LOCATION 1 ... 615 (xi) SEQUENCE DESCRIPTION: Sequence £. 94:

ATGCAAGGGT TTCTTTTACA AACACAAAGC ATAAGAGATG AAGATTTGAT CGTGCACGTT 60 TTAACCAAAA ACCAGCTCAA AACCCTCTAT CGTTTCTATG GCAAACGCCA CAGCGTGCTG 120 AATGTGGGTC GTAAAATTGA TTTTGAAGAA GAAAACGATG ATAAATTTTT ACCCAAGTTA 180 AGGAATATTT TGCATTTAGG CTATATTTGG GAAAGAGAAA TGGAGCGCTT GTTTTTTTGG 240 CAACGCTTTT GCGCTCTTTT GTTCAAGCAT TTAGAGGGCG TGCATTCTTT AGATAGCATC 300 TATTTTGACA CTTTAGATGA TGGGGCTAGC AAACTCTCCA AACAGCACCC CTTAAGAGTG 360 ATTTTAGAAA TGTATGCAGT CCTTTTGAAT TTTGAAGGGC GCTTGCAAAG TTACAATTCT 420 TGTTTTTTAT GCGATGCAAA ATTAGAGCGT TCTGTCGCTT TAGCGCAAGG GTTTATTTTA 480 GCGCACCCCT CTTGCTTGAA AGCTAAAAGC TTGGATTTAG AAAAAATCCA AGCTTTTTTC 540 CGCACTCAAA GCACGATTGA TCTAGAAACA GAAGAAGTGG AAGAATTATG GCGCACGCTG 600 AATTTAGGGT TTTGA 615

(2) INFORMATION FOR SEQUENCE NO. 95:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 249 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular (ii) MOLECULA TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE : NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) NAME / KEY: various characters (B) LOCATION 1 ... 249 (xi) SEQUENCE DESCRIPTION: Sequence no. 95:

ATGGGCGTCG GACGGGTCGG CAATATGGCA CTGTTGGCGT GTGCAGGTCC GATGGGCATC 60

GGCGCTATTG CTATCGCCAT TAACGGCGGC AGACAACGGT CGCGGATGTT GGTGGTCGAT 120

ATAGACGACA AACGTCTGGA GCAGGTACAG AAGATGCTGC CGGGGAATTG GCGGCCAGTA 180

222

ACGGCATTGA GCTGGTGTCT GTGCATACCA AAGCGAGGAG CGATCCGTGC CAGATGCTGC 240 GAGCGCTGA 249 (2) INFORMATION FOR SEQUENCE NO. 96:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 204 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular (ii) MOLECULAR TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE : NO (vi, ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) NAME / KEY: various characters (B) LOCATION 1 ... 204 (xi) SEQUENCE DESCRIPTION: Sequence no. 96:

TTGTCCGGTA CAGCCGTGAG TTGCCGGTGC ACATGCCGCA TACAGTTGGT ATTGGTGCGC 60 ACCAGCATCC CGGTTGTTAT CGGGTGCTCA TGCCCATTCC TTTCCAGTAT TGGGTTCACA 120 ACGGGAACCC ACCAATCACC CGTTAAACGC TGCGGGGTTA ACGCCGGAAA AACACCGTCA AAAAAACATT TGCATTTAAA 180 CTAA 204 (2) INFORMATION FOR SEQ ID NO. 97:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 345 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular (ii) MOLECULA TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE : NOT

223 (vi) ORIGINAL SOURCE:

(A) ORGANISM: (Ix) SIGN: (A) (B) NAME / KEY: PLACEMENT (Xi) SEQUENCE DESCRIPTION:

Helicobacter pylori various characters 1 ... 345

Sequence # 97:

GTGTGGCTGG

ATCGCCCTGG

CCGGCGGCCT

GCACCGCCAC

CGGCGCTGTT

CCGGTCGCCT

CGGCGCTGGG

CCAAGGTCGG

GCTGGCGGCG

GGTGTCCTTC

CGTCTACAGC

GCTGGACACC

CTTCCTGATC

CGGTTCGTCG

GTCTGCTACC

GAAGGTCAGC

CTGGCGTACT

GTCGGACGCT

ACCGCGGTGG

ACGCCCTCAG

TGGCGGTCGG

GTGGTGCCGC

TCCTCCTCGC

TCCTCGCCCC

GGCTGCCGGT GATCACCGTG CCATCCGATC GGCAGGTATG CCCGCTGTTC GCCATTCCGC TGCTCGGCGA AGAAGCGGCA CCTGGCCATC TCCCTCTACC

120

180

240

300

345 (2) INFORMATION FOR SEQUENCE NO. 98:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 228 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULA TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) NAME / KEY: various characters (B) LOCATION 1 ... 228 (xi) SEQUENCE DESCRIPTION: Sequence no. 98:

Met Arg Phe Lys Gly Ser Arg wall Glu Ala Phe Leu Gly Ala Leu Glu 1 5 10 15 Phe gin Glu same time Glu Tyr Glu Glu Phe Lys Glu Leu Tyr Glu Ser Leu 20 25 30 Lys Thr Lys gin Lys for His Thr Leu Phe Ile Ser Cys wall Asp Ser 35 40 45 Arg wall wall for same time Leu Ile Thr Gly Thr gin for Gly Glu Leu Tyr

224

50 55 60 wall Ile Arg same time Met Gly same time wall Ile for for Lys Thr Ser Tyr Lys 65 70 75 80 Glu Ser Leu Ser Thr Ile Ala Ser wall Glu Tyr Ala Ile Ala His wall 85 90 95 Gly wall gin same time Leu Ile Ile Cys Gly His Ser Asp Cys Gly Ala Cys 100 105 110 Gly Ser Ile His Leu Ile His Asp Glu Thr Thr Lys Ala Lys Thr for 115 120 125 Tyr Ile Ala same time Trp Ile gin Phe Leu Glu for Ile Lys Glu Glu Leu 130 135 140 Lys same time His for gin Phe Ser same time His Phe Ala Lys Arg Ser Trp Leu 145 150 155 160 Thr Glu Arg Leu same time Ala Arg Leu gin Leu same time same time Leu Leu Ser Tyr 165 170 175 Asp Phe Ile gin Glu Arg wall Ile same time same time Glu Leu Lys Ile Phe Gly 180 185 190 Trp His Tyr Ile Ile Glu Thr Gly Arg Ile Tyr same time Tyr same time Phe Glu 195 200 205 Ser His Phe Phe Glu for Ile Glu Glu Thr Ile Lys gin Arg Ile Ser 210 215 220

His Glu Asn Phe

225 (2) INFORMATION FOR SEQUENCE NO. 99:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 221 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULA TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL:

(A) ORGANISM: Helicobacter pylori (ix) SIGN (A) NAME / KEY: Differently letters (B) PLACEMENT 1. . . 221

(xi) SEQUENCE DESCRIPTION: SEQ ID NO. 99:

225

wall Glu Ala Phe Leu Gly Ala Leu Glu Phe gin Glu same time Glu Tyr Glu 1 5 10 15 Glu Phe Lys Glu Leu Tyr Glu Ser Leu Lys Thr Lys gin Lys for His 20 25 30 Thr Leu Phe Ile Ser Cys wall Asp Ser Arg wall wall for same time Leu Ile 35 40 45 Thr Gly Thr gin for Gly Glu Leu Tyr wall Ile Arg same time Met Gly same time 50 55 60 wall Ile for for Lys Thr Ser Tyr Lys Glu Ser Leu Ser Thr Ile Ala 65 70 75 80 Ser wall Glu Tyr Ala Ile Ala His wall Gly wall gin same time Leu Ile Ile 85 90 95 Cys Gly His Ser Asp Cys Gly Ala Cys Gly Ser Ile His Leu Ile His 100 105 110 Asp Glu Thr Thr Lys Ala Lys Thr for Tyr Ile Ala same time Trp Ile gin 115 120 125 Phe Leu Glu for Ile Lys Glu Glu Leu Lys same time His for gin Phe Ser 130 135 140 same time His Phe Ala Lys Arg Ser Trp Leu Thr Glu Arg Leu same time Ala Arg 145 150 155 160 Leu gin Leu same time same time Leu Leu Ser Tyr Asp Phe Ile gin Glu Arg wall 165 170 175 Ile same time same time Glu Leu Lys Ile Phe Gly Trp His Tyr Ile Ile Glu Thr 180 185 190 Gly Arg Ile Tyr same time Tyr same time Phe Glu Ser His Phe Phe Glu for Ile 195 200 205 Glu Glu Thr Ile Lys gin Arg Ile Ser His Glu same time Phe

210 215 220 (2) INFORMATION FOR SEQUENCE NO. 100:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 335 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULA TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

226 (A) TITLE / KEY: various characters (B) LOCATION 1 ... 335 (xi) SEQUENCE DESCRIPTION: Sequence no. 100:

Met Leu wall Thr Arg Phe Lys Lys Ala Phe Ile Ser Tyr Ser Leu Gly 1 5 10 15 wall Leu wall wall Ser Leu Leu Leu same time wall Cys same time Ala Ser Ala gin 20 25 30 Glu wall Lys wall Lys Asp Tyr Phe Gly Glu gin Thr Ile Lys Leu for 35 40 45 wall Ser Lys Ile Ala Tyr Ile Gly Ser Tyr wall Glu wall for Ala Met 50 55 60 Leu same time wall Trp Asp Arg wall wall Gly wall Ser Asp Tyr Ala Phe Lys 65 70 75 80 Asp Asp Ile wall Lys Ala Thr Leu Lys Gly Glu Asp Leu Lys Arg wall 85 90 95 Lys His Met Ser Thr Asp His Thr Ala Ala Leu same time wall Glu Leu Leu 100 105 110 Lys Lys Leu Ser for Asp Leu wall wall Thr Phe wall Gly same time for Lys 115 120 125 Ala wall Glu His Ala Lys Lys Phe Gly Ile Ser Phe Leu Ser Phe gin 130 135 140 Glu Thr Thr Ile Ala Glu Ala Met gin Ala Met gin Ala gin Ala Thr 145 150 155 160 wall Leu Glu Ile Asp Ala Ser Lys Lys Phe Ala Lys Met gin Glu Thr 165 170 175 Leu Asp Phe Ile Ala Glu Arg Leu Lys Gly wall Lys Lys Lys Lys Gly 180 185 190 wall Glu Leu Phe His Lys Ala same time Lys Ile Ser Gly His gin Ala Ile 195 200 205 Ser Ser Asp Ile Leu Glu Lys Gly Gly Ile Asp same time Phe Gly Leu Lys 210 215 220 Tyr wall Lys Phe Gly Arg Ala Asp Ile Ser wall Glu Lys Ile wall Lys 225 230 235 240 Glu same time for Glu Ile Ile Phe Ile Trp Trp wall Ser for Leu Thr for 245 250 255 Glu Asp wall Leu same time same time for Lys Phe Ser Thr Ile Lys Ala Ile Lys 260 265 270 same time Lys gin wall Tyr Lys Leu for Thr Met Asp Ile Gly Gly for Arg 275 280 285 Ala for Leu Ile Ser Leu Phe Ile Ala Leu Lys Ala His for Glu Ala 290 295 300 Phe Lys Gly wall Asp Ile same time Ala Ile wall Lys Asp Tyr Tyr Lys wall

227

305 310 315 320

Val Phe Leu Asn Asp Ala Glu White Glu For Phe Leu Trp His

325 330 335 (2) INFORMATION FOR SEQUENCE NO. 101:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 274 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULA TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (Ix) SIGN: (A) TITLE / KEY: different characters (B) LOCATION 1 ... 274 (Xi) SEQUENCE DESCRIPTION: Sequence £. 101:

Met Leu wall Thr Arg Phe Lys Lys Ala Phe Ile Ser Tyr Ser Leu Gly 1 5 10 15 wall Leu wall wall Ser Leu Leu Leu same time wall Cys same time Ala Ser Ala gin 20 25 30 Glu wall Lys wall Lys Asp Tyr Phe Gly Glu gin Thr Ile Lys Leu for 35 40 45 wall Ser Lys Ile Ala Tyr Ile Gly Ser Tyr wall Glu wall for Ala Met 50 55 60 Leu same time wall Trp Asp Arg wall wall Gly wall Ser Asp Tyr Ala Phe Lys 65 70 75 80 Asp Asp Ile wall Lys Ala Thr Leu Lys Gly Glu Asp Leu Lys Arg wall 85 90 95 Lys His Met Ser Thr Asp His Thr Ala Ala Leu same time wall Glu Leu Leu 100 105 110 Lys Lys Leu Ser for Asp Leu wall wall Thr Phe wall Gly same time for Lys 115 120 125 Ala wall Glu His Ala Lys Lys Phe Gly Ile Ser Phe Leu Ser Phe gin 130 135 140 Glu Thr Thr Ile Ala Glu Ala Met gin Ala Met gin Ala gin Ala Thr 145 150 155 160

228

Val Leu Glu White Asp 165 Ala Ser Lys Lys Phe Ala Lys Gin Glu Thr 170 175 Leu Asp Phe White Ala Asp Arg Leu Lys Gly Val Lys Lys 180 185 190 Val Glu Leu Phe Lys Ala Asn Lys Ile Ser Gly His Gin Ala White 195 200 205 Asn Ser Asp Leu Gin Gin Gly Gly Ile Asp Asn Phe Gly Leu Lys 210 215 220 Tyr Val Lys Arg Ala Asp ile Ser Val Glu Lys White Val Lys 225 230 235 240 Glu Asn For Glu White Arg Phe Arg Trp Val Thr Pro 245 250 255 Asp Tyr Val Leu Asn Asn Lys Phe Ser Thr ile Asn Ala ile Lys 260 265 270 Asn ile (2) INFORMATION FOR SEQUENCE NO. 102:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 428 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULA TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) TITLE / KEY: various characters (B) LOCATION 1 ... 428 (xi) SEQUENCE DESCRIPTION: Sequence no. 102:

Met Lys Lys Lys Phe Leu Ser Leu Thr Leu Gly Ser Leu Leu wall Ser 1 5 10 15 Ala Leu Ser Ala Glu Asp same time Gly Phe Phe wall Ser Ala Gly Tyr gin 20 25 30 Ile Gly Glu Ser Ala gin Met wall Lys same time Thr Lys Gly Ile gin Asp 35 40 45 Leu Ser Asp Ser Tyr Glu Arg Leu same time same time Leu Leu Thr same time Tyr Ser

229

wall Leu same time Ala Leu Ile Arg gin Ser Ala Asp for same time Ala Ile same time 65 70 75 80 same time Ala Arg Gly same time Leu same time Ala Ser Ala Lys same time Leu Ile same time Asp 85 90 95 Lys Lys same time Ser for Ala Tyr gin Ala wall Leu Leu Ala Leu same time Ala 100 105 110 Ala Ala Gly Leu Trp gin wall Met Ser Tyr Ala Ile Ser for Cys Gly 115 120 125 for Gly Lys Asp Thr Ser Lys same time Gly Gly wall gin Thr Phe His same time 130 135 140 Thr for Ser same time gin Trp Gly Gly Thr Thr Ile Thr Cys Gly Thr Thr 145 150 155 160 Gly Tyr Glu for Gly for Tyr Ser Ile Leu Ser Thr Glu same time Tyr Ala 165 170 175 Lys Ile same time Lys Ala Tyr gin Ile Ile gin Lys Ala Phe Gly Ser Ser 180 185 190 Gly Lys Asp Ile for Ala Leu Ser Asp Thr same time Thr Glu Leu Lys Phe 195 200 205 Thr Ile same time Lys same time same time Gly same time Thr same time Thr same time same time same time Gly Glu 210 215 220 Glu Ile wall Thr Lys same time same time Ala gin wall Leu Leu Glu gin Ala Ser 225 230 235 240 Thr Ile Ile Thr Thr Leu same time Ser Ala Cys for Trp Ile same time same time Gly 245 250 255 Gly Ala Gly Gly Ala Ser Ser Gly Ser Leu Trp Glu Gly Ile Tyr Leu 260 265 270 Lys Gly Asp Gly Ser Ala Cys Gly Ile Phe Lys same time Glu Ile Ser Ala 275 280 285 Ile gin Asp Met Ile Lys same time Ala Ala Ile Ala wall Glu gin Ser Lys 290 295 300 Ile wall Ala Ala same time Ala gin same time gin Arg same time Leu Asp Thr Gly Lys 305 310 315 320 Thr Phe same time for Tyr Lys Asp Ala same time Phe Ala gin Ser Met Phe Ala 325 330 335 same time Ala Lys Ala gin Ala Glu Ile Leu same time Arg Ala gin Ala wall wall 340 345 350 Lys Asp Phe Glu Arg Ile for Ala Glu Phe wall Lys Asp Ser Leu Gly 355 360 365 wall Cys His Glu wall gin same time Gly His Leu Arg Gly Thr for Ser Gly 370 375 380 Thr wall Thr Asp same time Thr Trp Gly Ala Gly Cys Ala Tyr wall Gly Glu 385 390 395 400 Thr wall Thr same time Leu Lys Asp Ser Ile Ala His Phe Gly Asp gin Ala

230

405 410 415

Glu Arg ile His Asn Ala As Arg Asn Leu Ala Thr Leu

420 425 (2, INFORMATION FOR SEQUENCE No. 103:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 178 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULA TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (Ix) SIGN: (A) NAME / KEY: different characters (B) PLACEMENT 1 ... 178 (Xi. DESCRIPTION 1 SEQUENCE: Sequence ô. 103:

Met same time for Leu Leu gin Asp Tyr Ala Arg Ile Leu Leu Glu Trp same time 1 5 10 15 gin Thr His same time Leu Ser Gly Ala Arg same time Leu Ser Glu Leu Glu for 20 25 30 gin Ile Thr Asp Ala Leu Lys for Leu Glu Phe wall Lys Asp Phe Lys 35 40 45 Ser Cys Leu Asp Ile Gly Ser Gly Ala Gly Leu for Ala Ile for Leu 50 55 60 Ala Leu Glu Lys for Glu Ala gin Phe Ile Leu Leu Glu for Arg wall 65 70 75 80 Lys Arg Ala Ala Phe Leu same time Tyr Leu Lys Ser wall Leu for Leu same time 85 90 95 same time Ile Glu Ile Ile Lys Lys Arg Leu Glu Asp Tyr gin same time Leu Leu 100 105 110 gin wall Asp Leu Ile Thr Ser Arg Ala wall Ala Ser Ser Ser Phe Leu 115 120 125 Ile Glu Lys Ser gin Arg Phe Leu Lys Asp Lys Gly Tyr Phe Leu Phe 130 135 140 Tyr Lys Gly Glu gin Leu Lys same time Glu Ile Ala Tyr Lys Thr Thr Glu 145 150 155 160

231

Cys Phe Met His Gin Lys Arg Val Tyr Phe Tyr Lys Ser Lys Glu 165 170 175 Leu Cys (2, INFORMATION FOR SEQUENCE NO. 104:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 240 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULA TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) NAME / KEY: various characters (B) LOCATION 1 ... 240 (xi, SEQUENCE DESCRIPTION: Sequence £ 104:

Leu Gly Leu Lys Lys Arg Ala Ile Leu Trp Ser Leu Met Gly Phe Cys 1 5 10 15 Ala Gly Leu Ser Ala Leu Asp Tyr Asp Thr Leu Asp for Lys Tyr Tyr 20 25 30 Lys Tyr Ile Lys Tyr Tyr Lys Ala Tyr Glu Asp Lys Glu wall Glu Glu 35 40 45 Leu Ile Arg Asp Leu Lys Arg Ala same time Ala Lys Ser Gly Leu Ile Leu 50 55 60 Gly Ile same time Thr Gly Phe Phe Tyr same time His Glu Ile Met wall Lys Thr 65 70 75 80 same time Ser Ser Ser Ile Thr Gly same time Ile Leu same time Tyr Leu Phe Ala Tyr 85 90 95 Gly Leu Arg Phe Gly Tyr gin Thr Phe Arg for Ser Phe Phe Ala Arg 100 105 110 Leu wall Lys for same time Ile Ile Gly Arg Arg Ile Tyr Ile gin Tyr Tyr 115 120 125 Gly Gly Ala for Lys Lys Ala Gly Phe Gly Ser wall Gly Phe gin Ser 130 135 140 wall Met Leu same time Gly Asp Phe Leu Leu Asp Phe for Leu for Phe wall

232

145 150 155 160 Gly Lys Tyr Leu Tyr Met Gly Gly Tyr Met Gly Leu Gly Leu Gly wall 165 170 175 wall Ala His Gly wall same time Tyr Thr Ala Glu Trp Gly Met Ser Phe same time 180 185 190 Ala Gly Leu Ala Leu Thr wall Leu Glu Lys same time Arg Ile Glu Phe Glu 195 200 205 Phe Lys Ile Leu same time same time Phe for Phe Leu gin Ser same time Ser Ser Lys 210 215 220 Glu Thr Trp Trp Gly Ala Ile Ala Ser Ile Gly Tyr gin Tyr wall Phe 225 230 235 240

(2) INFORMATION FOR SEQUENCE NO. 105:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 313 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULA TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix) SIGN: (A) NAME / KEY: Differently letters (B) PLACEMENT 1. . . 313

(xi) SEQUENCE DESCRIPTION: SEQ ID NO. 105:

Leu Lys Leu Lys Tyr Trp Leu wall Tyr Leu Ala Phe Ile Ile Gly Leu 1 5 10 15 gin Ala Thr Asp Tyr Asp same time Leu Glu Glu Glu same time gin gin Leu Asp 20 25 30 Glu Lys Ile same time same time Leu Lys Arg gin Leu Thr Glu Lys Gly wall Ser

40

Lys Glu Met Lys Asp Lys Asp Lys 50 55 Thr Tyr for Lys Ile Ser Ser Lys 65 70 Phe Ser Ile Ala Asp Asp Lys Ser 85

Phe Glu Glu Glu Tyr Leu Glu Arg 60 Lys Arg Lys Lys Leu Leu Lys Ser 75 80 Gly wall Phe Leu Gly Gly Gly Tyr 90 95

233

Ala Tyr Gly Glu Leu Asn Leu Tyr Gin Gly Met Leu Asp Arg 100 105 110 Tyr Gly Ala same time Ala for Ser Ala Phe Lys same time same time Ile same time Ile same time 115 120 125 Ala for wall Ser Met Ile Ser wall Lys Phe Gly Tyr gin Lys Tyr Phe 130 135 140 wall for Tyr Phe Gly Thr Arg Phe Tyr Gly Asp Leu Leu Leu Gly Gly 145 150 155 160 Gly Ala Leu Lys Glu same time Ala Leu Lys gin for wall Gly Ser Phe Phe 165 170 175 Tyr wall Leu Gly Ala Met same time Thr Asp Leu Leu Phe Asp Met for Leu 180 185 190 Asp Phe Lys Thr Lys Lys His Phe Leu Gly wall Tyr Ala Gly Phe Gly 195 200 205 Ile Gly Leu Met Leu Tyr gin Asp Lys for same time gin same time Gly Arg same time 210 215 220 Leu Ile wall Gly Gly Tyr Ser Ser for same time Phe Leu Trp Lys Ser Leu 225 230 235 240 Ile Glu wall Asp Tyr Thr Phe same time wall Gly wall Ser Leu Thr Leu Tyr 245 250 255 Arg Lys His Arg Leu Glu Ile Gly Thr Lys Leu for Ile Ser Tyr Leu 260 265 270 Arg Met Gly wall Glu Glu Gly Ala Ile Tyr His same time Lys Glu same time Asp 275 280 285 Glu Arg Leu Leu Ile Ser Ala same time same time gin Phe Lys Arg Ser Ser Phe 290 295 300 Leu Leu wall same time Tyr Ala Phe Ile Phe

305 310 (2) INFORMATION FOR SEQUENCE NO. 106:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 393 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULAR TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

234 (A) NAME / KEY: miscellaneous characters (B) LOCATION 1 ... 393 (xi) SEQUENCE DESCRIPTION: Sequence no. 106:

Met Thr Ser Ala Ser Ser His Ser Phe Lys Glu Gin Asp Phe His White 15 10 15

Ala Phe Ala Ala Phe Asp Lys Asn Tyr Leu Ala Ala Gly Ala

25 30

Cys White Tyr Ser Leu Leu Glu Ser White Ala Lys Ala Asn Lys Lys White

40 45

Arg Tyr Thr Leu As Ala Glu Asp Lys

55 60

Thr Lys Leu Asn Gin White Thr Glu Pro Phe Lys Glu Phe Ala Val Leu

70

Glu Val Lys Asp Glu Pro Phe Leu Asp Thr Pro Pro Asn Pro Phe

90 95

Asp Glu Phe Thr Lys Met Ph Le Ser Val Leu Val Lys Tyr

100 105 110

Phe Leu Ala Asp Leu Phe Lys Tyr Ser Lys Met Val Trp Ser Asp

115 120 125

Val Asp Val White Phe Cys Asn Glu Phe Ser Ala Asp Phe Leu Asn White

129 135 140

Lys Glu Asp Asp Glu Asn Tyr Phe Tyr Gly Val Tyr Asp Lys White Tyr

145 150 155 160

Pro Tyr Glu Phly Phe Tyr Cys Asn Leu Thr Tyr Gin Arg Lys Asn

165 170 175

Gin Phe Cys Lys Lys White Leu Glu Lines Arg Ala Gin Lys White Asp

180 185 190

Lys Glu Pro Gin Leu Thr Glu Phe Cys Arg Ser Lys White Ala Pro Leu

195 200 205

Lys White Glu Tyr Cys White Phe Pro His Tyr Tyr Ser Leu Ser Glu Glu

210 215 220

His Leu Lys Gly Val Ala Asn Ala White Tyr His Asn Thr White Lys Gin

(+420) 225 230 235 240

Ala Leu Arg Glu Pro ile Val ile Gin Tyr Asp Ser His Pro Tyr Phe

245

Gin White Lys Pro Trp Thr Tyr Pro Phy Gly Leu Lys Ala Asp Leu Trp

260 265 270

Leu Asn Ala Leu Ala Lys Thr

275 280 285 Thr Gly Gly Gly Gly Gly Gly Glu Lys

290 295 300

Gly White Ala Ala Tyr His Tyr Tyr Phe Pro Leu Trp Lys Ala Glu Glu

235

305 310 315 320

gin Ile Lys His Tyr Phe Leu 325 330 335 His Ile His Glu Ile for gin same time Ala Arg Arg Arg Leu Phe Lys Tyr 340 345 350 Cys Ile Ser Ile for Leu Lys Ser Phe Ile Ser Lys Thr Leu Lys Phe 355 360 365 Leu Lys Leu His Ala Leu wall Lys Lys Ile Leu Ile gin Leu Lys Leu 370 375 380 Leu Lys Lys same time gin Ser gin same time Phe

385 390 (2) INFORMATION FOR SEQUENCE NO. 107:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 435 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULA TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix) SIGN (A) NAME / KEY: different characters (B, PLACEMENT 1 ... 434

(xi) SEQUENCE DESCRIPTION: SEQ ID NO. 107:

Leu Ile Phe Leu Lys Lys Ser Leu Cys Ala Leu Leu Ile Ser Gly Phe 1 5 10 15 Phe Ile for for Leu Met Lys Ala Ala Ser Phe wall Tyr Asp Leu Lys 20 25 30 Phe Met Ser Phe same time Phe same time Leu Ala Ser for for same time same time for Tyr 35 40 45 Trp same time Ser Leu Thr Lys Met gin Gly Arg Leu Met for gin Ile Gly 50 55 60 wall gin Leu Asp Lys Arg gin Ala Leu Met Phe Gly Ala Trp Phe Ile 65 70 75 80 gin same time Leu His Thr His Tyr Ser Tyr Phe for Tyr Ser Trp Gly wall 85 90 95

236

Thr Met Tyr Tyr 100 Gin Tyr Il Gly Lys Asn Leu Arg Phe Phe Leu Gly 105 110 Ile wall for Arg Ser Tyr gin Ile Gly His Tyr for Leu Ser Ala Phe 115 120 125 Lys Lys Leu Phe Trp Phe Ile Asp for Thr Phe Arg Gly Gly Ala Phe 130 135 140 gin Phe Lys for Ala Tyr Asp for same time Arg Trp Trp same time Gly Trp Phe 145 150 155 160 Glu Gly wall wall Asp Trp Tyr Gly Gly Arg same time Trp same time same time gin for 165 170 175 Lys Lys Lys same time Tyr Asp Phe Asp gin Phe Leu Tyr Phe wall Ser Ser 180 185 190 Glu Phe gin Phe Leu Lys Gly Tyr Leu Gly Leu Gly Gly gin Leu wall 195 200 205 Ile Phe His same time Ala same time Ser His Ser Met Gly Asp same time Tyr for Tyr 210 215 220 Gly Gly same time Ser Tyr Leu Lys for Gly Asp Ala Thr for gin Trp for 225 230 235 240 same time Gly Tyr for Tyr Phe Ser gin Lys Asp same time for gin Gly Gly Glu 245 250 255 Ile dy Lys Tyr Ser same time for Thr Ile Leu Asp Arg wall Tyr Tyr His 260 265 270 Ala Tyr Leu Lys Ala Asp Phe Lys same time Leu Met for Tyr Met Asp same time 275 280 285 Ile Phe Met Thr Phe Gly Thr gin Ser Ser gin Thr His Tyr Cys wall 290 295 300 Arg Tyr Ala Ser Glu Cys Lys same time Ala Arg Phe Tyr same time Ser Phe Gly 305 310 315 320 Gly Glu Phe Tyr Ala gin Ala gin Tyr Lys Gly Phe Gly Ile Phe same time 325 330 335 Arg Tyr Tyr Phe Ser same time Lys for gin Met His Phe Tyr Ala Thr Tyr 340 345 350 Gly gin Ser Leu Tyr Thr Gly Leu for Trp Tyr Arg Ala for same time Phe 355 360 365 Asp Met Ile Gly Leu Tyr Tyr Leu Tyr Lys same time Lys Trp Leu Ser wall 370 375 380 Arg Ala Asp Ala Phe Phe Ser Phe wall Gly Gly Gly Asp Gly Tyr His 385 390 395 400 Leu Tyr Gly Lys Gly Gly Lys Trp Phe wall Met Tyr gin gin Phe Leu 405 410 415 Thr Leu Thr Ile Asp Thr Arg Glu Leu Ile Asp Phe wall Lys Ser Lys 420 425 430 Ile for Lys 435

237 (2) INFORMATION FOR SEQUENCE NO. 108:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 220 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULA TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) NAME / KEY: various characters (B) LOCATION 1 ... 220 (xi) SEQUENCE DESCRIPTION: Seq. 108:

Met same time Lys Thr Thr Ile Lys Ile Leu Met Gly Met Ala Leu Leu Ser 1 5 10 15 Ser Leu gin Ala Ala Glu Ala Glu Leu Asp Glu Lys Ser Lys Lys for 20 25 30 Lys Phe Ala Asp Arg same time Thr Phe Tyr Leu Gly wall Gly Tyr gin Leu 35 40 45 Ser Ala Ile same time Thr Ser Phe Ser Thr Ser Ser Ile Asp Lys Ser Tyr 50 55 60 Phe Met Thr Gly same time Gly Phe Gly wall wall Leu Gly Gly Lys Phe wall 65 70 75 80 Ala Lys Thr gin Ala wall Glu His wall Gly Phe Arg Tyr Gly Leu Phe 85 90 95 Tyr Asp gin Thr Phe Ser Ser His Lys Ser Tyr Ile Ser Thr Tyr Gly 100 105 110 Leu Glu Phe Ser Gly Leu Trp Asp Ala Phe same time Ser for Lys Met Phe 115 120 125 Leu Gly Leu Glu Phe Gly Leu Gly Ile Ala Gly Ala Thr Tyr Met for 130 135 140 Gly Gly Ala Met His Gly Ile Ile Ala gin Tyr Leu Gly Lys Glu same time 145 150 155 160 Ser Leu Phe gin Leu Leu wall Lys wall Gly Phe Arg Phe Gly Phe Phe 165 170 175 His same time Glu Ile Thr Phe Gly Leu Lys Phe for wall Ile for same time Lys

238

180 185 190 Lys Thr Glu Ile wall Asp Gly Leu Ser Ala Thr Thr Leu Trp 195 200 205 Leu for wall Ala Tyr Phe Asn Tyr Ile Tyr same time Phe 210 215 220

(2) INFORMATION FOR SEQUENCE NO. 109:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 116 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULA TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix) SIGN: (A) NAME / KEY: Differently letters (B) PLACEMENT 1 ... 116

(xi) SEQUENCE DESCRIPTION: SEQ ID NO. 109:

Leu same time Leu His Phe Met Lys Gly Phe wall Met Ser Gly Leu Arg 1 5 10 15 Phe Ser Cys wall wall wall Leu Cys Gly Ala Met wall same time wall Ala 20 25 30 Ala Gly for Lys Ile Glu Ala Arg Gly Glu Leu Gly Lys Phe wall 35 40 45 Gly Ala wall Gly same time Phe wall Gly Asp Lys Met Gly Gly Phe wall 50 55 60 Gly Ala Ile Gly Gly Tyr Ile Gly Ser Glu wall Gly Asp Arg wall 65 70 75 Asp Tyr Ile Arg Gly wall Asp Arg Glu for gin same time Lys Glu for 85 90 95 Thr for Arg Glu for Ile Arg Asp Phe Tyr Asp Tyr Gly Tyr Ser 100 105 110

Thr

wall

Gly

Gly

Glu

gin

Phe

Gly His Ala Trp 115 (2) 110

239 (i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 436 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULA TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) NAME / KEY: various characters (B) LOCATION 1 ... 436 (xi) SEQUENCE DESCRIPTION: Sequence no. 110:

Met Ser Arg Asp Phe Lys Phe Asp Ser same time Tyr Leu same time wall same time Thr 1 5 10 15 same time for Lys Leu Gly for wall Tyr Thr same time gin same time Tyr for Gly Phe 20 25 30 Phe Ile Phe Asp His Leu Arg Arg Tyr wall Met same time Ala Phe Glu for 35 40 45 same time Leu same time Leu wall wall same time Thr same time Lys wall Lys gin Thr Phe same time 50 55 60 wall Gly Met Arg Phe Met Thr Met Asp Met Phe Ile Arg Ser Asp gin 65 70 75 80 Ser Thr Cys Glu Lys Thr Asp Ile Ile same time Gly wall Cys His Met for 85 90 95 for Tyr wall Leu Ser Lys Thr for same time same time same time gin Glu Met Phe same time 100 105 110 same time Tyr Thr Ala wall Trp Leu Ser Asp Lys Ile Glu Phe Phe Asp Ser 115 120 125 Lys Leu wall Ile Thr for Gly Leu Arg Tyr Thr Phe Leu same time Tyr same time 130 135 140 same time Lys Glu for Glu Lys His Asp Phe Ser wall Trp Thr Ser Lys Lys 145 150 155 160 gin Arg gin same time Glu Trp Ser for Ala Leu same time Ile Gly Tyr Lys for 165 170 175 Met Glu same time Trp Ile Trp Tyr Ala same time Tyr Arg Arg Ser Phe Ile for 180 185 190 for gin His Thr Met wall Gly Ile Thr Arg Thr same time Tyr same time gin Ile

240

Phe same time 195 Glu Ile Glu wall Gly 200 gin Ser 210 Phe same time Thr same time Tyr 215 Phe wall 225 Gly Gly Tyr Ser for 230 gin for wall Leu Glu Leu Tyr 245 Tyr Ala for Ile Tyr Thr Tyr 260 Ile Asp Ala Arg Ile Tyr Tyr 275 Phe Thr Gly Ile wall 280 same time Arg 290 Leu for Tyr wall Ser 295 for same time 305 Thr Tyr Lys His Thr 310 Thr Phe Gly Ala Tyr Ser Ser 325 Met Leu same time gin for Leu same time 340 for Glu Tyr Thr Gly wall Gly 355 Leu Leu for Leu Tyr 360 Phe Ile 370 Leu Trp gin Ser Gly 375 Arg His 385 same time same time Leu Phe same time 390 Met Lys Tyr for Thr Gly Arg 405 Glu for Ala for

420

Asn Tyr Glu Phe 435 (2)

(I)

205

Arg Tyr Ser Tyr Lys Asn Leu Leu 220 Clay Phe Ala Lys Arg Tyr Tyr Ala 235 240

Asp Ala Arg - Ser Gin Gly Val Glu

250 255

Arg Gly Leu Gin Phe His Val Ala 265

Thr Ser Asn Ala Asp Asp Ala

285

Lys Pro Phe Asp Lys Gly Lys 300

Gin Phe White Phe Asp Met Met Tyr 315 320 White Ser Ser Tyr Phe Tyr Ser Arg

330 335

Ala Lys Gin Thr Val Cys Leu 345 350

Gly Leu Lys Tyr

365

Val Leu Asn Val Val Ser Ser 380

Lys White Thr Gly Ser Leu Gin White 395 400

Tyr Phe Arg Gly White Gly Thr Ser

410 415

Gly Arg Ser ile Thr Ala Tyr Leu 425,430

111:

SEQUENCE CHARACTERISTICS: (A) LENGTH (ii) (iii)

767 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear

MOLECULA TYPE: protein

HYPOTHETICAL: YES (vi) ORIGINAL SOURCE:

241 (A) ORGANISM: Helicobacter pylori (ix)

(A) NAME / KEY: various characters (B) LOCATION 1 ... 767 (xi) SEQUENCE DESCRIPTION: Sequence no. 111:

Met Lys Arg Ile Leu wall Ser Leu Ala wall Leu Ser His Ser Ala His 1 5 10 15 Ala wall Lys Thr His same time Leu Glu Arg wall Glu Ala Ser Gly wall Ala 20 25 30 same time Asp Lys Glu Ala for Leu Ser Trp Arg Ser Lys Glu wall Arg same time 35 40 45 Tyr Met Gly Ser Arg Thr wall Ile Ser same time Lys gin Leu Thr Lys Ser 50 55 60 Ala same time gin Ser Ile Glu Glu Ala Leu gin same time wall for Gly wall His 65 70 75 80 Ile Arg same time Ser Thr Gly Ile Gly Ala wall for Ser Ile Ser Ile Arg 85 90 95 Gly Phe Gly Ala Gly Gly for Gly His Ser same time Thr Gly Met Ile Leu 100 105 110 wall same time Gly Ile for Ile Tyr wall Ala for Tyr wall Glu Ile Gly Thr 115 120 125 wall Ile Phe for wall Thr Phe gin Ser wall Asp Arg Ile Ser wall Thr 130 135 140 Lys Gly Gly Glu Ser wall Arg Tyr Gly for same time Ala Phe Gly Gly wall 145 150 155 160 Ile same time Ile Ile Thr Lys Gly Ile for Thr same time Trp Glu Ser gin wall 165 170 175 Ser Glu Arg Thr Thr Phe Trp Gly Lys Ser Glu same time Gly Gly Phe Phe 180 185 190 same time gin same time Ser Lys same time Ile Asp Lys Ser Leu wall same time same time Met Leu 195 200 205 Phe same time Thr Tyr Leu Arg Thr Gly Gly Met Met same time Lys His Phe Gly 210 215 220 Ile gin Ala gin wall same time Trp Leu Lys Gly gin Gly Phe Arg Tyr same time 225 230 235 240 Ser for Thr Asp Ile gin same time Tyr Met Leu Asp Ser Leu Tyr gin Ile 245 250 255 same time Asp Ser same time Lys Ile Thr Ala Phe Phe gin Tyr Tyr Ser Tyr Phe 260 265 270 Leu Thr Asp for Gly Ser Leu Gly Ile Ala Ala Tyr same time gin same time Arg 275 280 285

242

Phe gin same time same time Arg for same time same time Asp Lys Ser Gly Arg Ala Lys Arg 290 295 300 Trp Gly Ala wall Tyr gin same time Phe Phe Gly Asp Thr Asp Arg wall Gly 305 310 315 320 Gly Asp Phe Thr Phe Ser Tyr Tyr Gly His Asp Met Ser Arg Asp Phe 325 330 335 Lys Phe Asp Ser same time Tyr Leu same time wall same time Thr same time for Lys Leu Gly 340 345 350 for wall Tyr Thr same time gin same time Tyr for Gly Phe Phe Ile Phe Asp His 355 360 365 Leu Arg Arg Tyr wall Met same time Ala Phe Glu for same time Leu same time Leu wall 370 375 380 wall same time Thr same time Lys wall Lys gin Thr Phe same time wall Gly Met Arg Phe 385 390 395 400 Met Thr Met Asp Met Phe Ile Arg Ser Asp gin Ser Thr Cys Glu Lys 405 410 415 Thr Asp Ile Ile same time Gly wall Cys His Met for for Tyr wall Leu Ser 420 425 430 Lys Thr for same time same time same time gin Glu Met Phe same time same time Tyr Thr Ala wall 435 440 445 Trp Leu Ser Asp Lys Ile Glu Phe Phe Asp Ser Lys Leu wall Ile Thr 450 455 4 60 for Gly Leu Arg Tyr Thr Phe Leu same time Tyr same time same time Lys Glu for Glu 465 470 475 480 Lys His Asp Phe Ser wall Trp Thr Ser Lys Lys gin Arg gin same time Glu 485 490 4 95 Trp Ser for Ala Leu same time Ile Gly Tyr Lys for Met Glu same time Trp Ile 500 505 510 Trp Tyr Ala same time Tyr Arg Arg Ser Phe Ile for for gin His Thr Met 515 520 525 wall Gly Ile Thr Arg Thr same time Tyr same time gin Ile Phe same time Glu Ile Glu 530 535 540 wall Gly gin Arg Tyr Ser Tyr Lys same time Leu Leu Ser Phe same time Thr same time 545 550 555 560 Tyr Phe wall Ile Phe Ala Lys Arg Tyr Tyr Ala Gly Gly Tyr Ser for 565 570 575 gin for wall Asp Ala Arg Ser gin Gly wall Glu Leu Glu Leu Tyr Tyr 580 585 590 Ala for Ile Arg Gly Leu gin Phe His wall Ala Tyr Thr Tyr Ile Asp 595 600 605 Ala Arg Ile Thr Ser same time Ala Asp Asp Ile Ala Tyr Tyr Phe Thr Gly 610 615 620 Ile wall same time Lys for Phe Asp Ile Lys Gly Lys Arg Leu for Tyr wall 625 630 635 640

243

Ser Pro Asn Gin Phe 645 Ile Phe Asp Met Met Tyr Thr Lys His Thr 650 655 Thr Phe Gly Ile Ser Ser Tyr Phe Tyr Ser Arg Ala Tyr Ser Ser Met 660 665 670 Leu same time gin Ala Lys Asp gin Thr wall Cys Leu for Leu same time for Glu 675 680 685 Tyr Thr Gly Gly Leu Lys Tyr Gly Cys same time Ser wall Gly Leu Leu for 690 695 700 Leu Tyr Phe wall Leu same time wall gin wall Ser Ser Ile Leu Trp gin Ser 705 710 715 720 Gly Arg His Lys Ile Thr Gly Ser Leu gin Ile same time same time Leu Phe same time 725 730 735 Met Lys Tyr Tyr Phe Arg Gly Ile Gly Thr Ser for Thr Gly Arg Glu 740 745 750 for Ala for Gly Arg Ser Ile Thr Ala Tyr Leu same time Tyr Glu Phe 755 760 765

(2) INFORMATION FOR SEQUENCE NO. 112:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 115 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULA TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) NAME / KEY: various characters (B) LOCATION 1 ... 115 (xi) SEQUENCE DESCRIPTION: Sequence no. 112:

Leu His for Leu Cys Ala His Gly gin Cys Gly Ser Glu Ala Ile Ala 1 5 10 15 Cys Leu Glu Ala Ile Ser wall Gly Ile wall for wall Ile Ala same time Ser 20 25 30 for Leu Ser Ala Thr Arg gin Phe Ala Leu Asp Glu Arg Ser Leu Phe 35 40 45 Glu for same time same time Ala Lys Asp Leu Ser Ala Lys Ile Asp Trp Trp Leu

244

50 55 60 Glu same time Lys Leu Glu Arg Glu Arg Met gin same time Glu Tyr Ala Lys Ser 65 70 75 80 Ala Leu same time Tyr Thr Leu Glu same time Ser wall Ile gin Ile Glu Lys wall 85 90 95 Tyr Glu Glu Ala Ile Lys Asp Phe Lys same time same time for same time Leu Phe Lys 100 105 110

Thr Leu Ser 115 (2) 113:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 389 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULA TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) NAME / KEY: various characters (B) LOCATION 1 ... 389 (xi) SEQUENCE DESCRIPTION: Sequence no. 113:

Met Val ile Val Leu Val Val Ser Ser Lys Asp Thr Ser Asn Gly 15 10 15

Thr Ser Met Thr Ala Phe Arg Phe Phe Glu

25 30

His Ala Met Arg Val Val For His Val Asp Asn Leu Gly Ser Glu

40 45

Glu Glu Gly Tyr Tyn Asn Leu Lys Glu Arg Tyr White Pro Leu Val Thr

55 60

Glu White Ser His Lys Gin His White Leu Phe Ala Lys For Asp Glu Lys

70 75 80 White Leu Arg Lys Ala Phe Lys Gly Ala Asp Met His Thr Tyr Leu

90 95

For Phe Leu Leu Glu Lys Thr Ala Val Lys Clay Ala Arg Glu Met Arg

100 105 110

245

Val Pro Tyr White Gly Ser Phe His Ser Tyr 115 120 125 same time Met Lys Leu Gly Gin Phe Ser Trp Leu Asn Thr Met Leu Phe 130 135 140 Trp Phe Lys Ser Ser His Tyr Arg Tyr ile His His ile His Cys Pro 145 150 155 160 Ser Lys Phe White Val Glu Glu Leu Glu Lys Tyr Asn Tyr Gly Gly Lys 165 170 175 Lys Tyr Ala ile Ser Asn Gly Phe Asp Pro Met Phe Lys Phe Glu His 180 185 190 for Gin Lys Ser Leu Phe Asp Thr Thr Pro Phe Lys White Ala Met Val 195 200 205 Gly Arg Tyr Ser Asn Glu Lys Asn Gin Ser Val Leu White Lys 210 215 220 Ala Leu Ser Arg Tyr Lys Gin Asp Val Leu Leu Leu Lys Gly Lys 225 230 235 240 Gly For Asp Glu Lys Lys White Lys Leu Leu Ala Gin Lys Gly Val 245 250 255 Lys Thr Glu Phe Gly Phe Val Asn Ser Glu Leu Leu Glu White Leu 260 265 270 Lys Thr Cys Thr Leu Tyr Ala His Thr Ala Asn Val Glu Ser Glu Ala 275 280 285 Ile Ala Cys Leu Glu Ala ile Ser Val Gly White Val Pro Val ile Ala 290 295 300 same time Ser Pro Leu Ser Ala Thr Arg Gin Phe Ala Leu Asp Glu Arg Ser 305 310 315 320 Leu Phe Glu Pro Asn Asn Ala Lys Asp Leu Ser Ala Lys Asp Trp 325 330 335 Trp Leu Glu Asn Lys Leu Arg Glu Arg Met Gin Asn Glu Tyr Ala 340 345 350 Lys Ser Ala Leu Asn Tyr Thr Leu Glu Asn Ser Val White Gin White Glu 355 360 365 Lys Val Glu Glu Ala and Lys Asp Phe Lys Asn Asn For Asn Leu 370 375 380 Phe Lys Thr Leu Ser 385 (2) INFORMATION FOR SEQUENCE NO. 114:

(i, SEQUENCE CHARACTERISTICS:

(A) LENGTH: 312 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear

246 (ii) MOLECULA TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix) SIGN (A) NAME / KEY: different characters (B) PLACEMENT 1 ... 312

(xi) SEQUENCE DESCRIPTION: SEQ ID NO. 114:

Leu Ala 1 Ser Tyr Gly Phe Phe Leu Gly Ala Leu Phe White Leu Ala Ser 5 10 15 Gly Ile wall Cys Leu gin Thr Ala Gly same time for Phe wall Thr Leu Leu 20 25 30 Ser Lys Gly Lys Glu Ala Arg same time Leu wall Leu wall gin Ala Phe same time 35 40 45 Ser Leu Gly Thr Thr Leu Gly for Ile Phe Gly Ser Leu Leu Ile Phe 50 55 60 Ser Ala Thr Lys Thr Ser Asp same time Leu Ser Leu Ile Asp Lys Leu Ala 65 70 75 80 Asp Ala Lys Ser wall gin Met for Tyr Leu Gly Leu Ala wall Phe Ser 85 90 95 Leu Leu Leu Ala Leu wall Met Tyr Leu Leu Lys Leu for Asp wall Glu 100 105 110 Lys Glu Met for Lys Glu Thr Thr gin Lys Ser Leu Phe Ser His Lys 115 120 125 His Phe wall Phe Gly Ala Leu Gly Ile Phe Phe Tyr wall Gly Gly Glu 130 135 140 wall Ala Ile Gly Ser Phe Leu wall Leu Ser Phe Glu Lys Leu Leu same time 145 150 155 160 Leu Asp Ala gin Ser Ser Ala His Tyr Leu wall Tyr Tyr Trp Gly Gly 165 170 175 Ala Met wall Gly Arg Phe Leu Gly Ser Ala Leu Met same time Lys Ile Ala 180 185 190 for same time Lys Tyr Leu Ala Phe same time Ala Leu Ser Ser Ile Ile Leu Ile 195 200 205 Ala Leu Ala Ile Leu Ile Gly Gly Lys Ile Ala Leu Phe Ala Leu Thr 210 215 220 Phe wall Gly Phe Phe same time Ser Ile Met Phe for Thr Ile Phe Ser Leu 225 230 235 240 Ala Thr Leu same time Leu Gly His Leu Thr Ser Lys Ala Ser Gly wall Ile

247

245

Ser Met Ala Val Gly Gly Ala Leu Ala Pro Pro Gin Gly Val 260 265 270 wall Thr Asp Met Leu Thr Ala Thr Glu Ser same time Leu Leu Tyr Ala Tyr 275 280 285 Ser wall for Leu Leu Cys Tyr Phe Tyr Ile Leu Phe Phe Ala Leu Lys 290 295 300 Gly Tyr Lys gin Glu Glu same time Ser 305 310

(2) INFORMATION FOR SEQUENCE NO. 115:

(1) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 407 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULA TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix) SIGN: (A) NAME / KEY: different characters (B) PLACEMENT 1 ... 407

(xi) SEQUENCE DESCRIPTION: SEQ ID NO. 115:

Met gin Lys Thr Ser same time Thr Leu Ala Leu Gly Ser Leu Thr Ala Leu 1 5 10 15 Phe Phe Leu Met Gly Phe Ile Thr wall Leu same time Asp Ile Leu Ile for 20 25 30 His Leu Lys for Ile Phe Asp Leu Thr Tyr Phe Glu Ala Ser Leu Ile 35 40 45 gin Phe Cys Phe Phe Gly Ala Tyr Phe Ile Met Gly Gly wall Phe Gly 50 55 60 same time wall Ile Ser Lys Ile Gly Tyr for Phe Gly wall wall Leu Gly Phe 65 70 75 80 wall Ile Thr Ala Ser Gly Cys Ala Leu Phe Tyr for Ala Ala His Phe 85 90 95 Gly Ser Tyr Gly Phe Phe Leu Gly Ala Leu Phe Ile Leu Ala Ser Gly 100 105 110

248 ile Val Cys Leu Gin Thr Ala Gly Asn Pro

Lys Gly Lys Glu Ala Phe Asn Ser

129 135 140

Leu Gly Thr Thr Leu Gly Pro Phe Gly Ser Leu Leu Phe Ser

145 150 155 160

Ala Thr Lys Thr Ser Asp Asn Leu Ser Leu Clay Asp Lys Leu Ala Asp

165 170 175

Ala Val Phe Ser Leu

180 185 190

Leu Leu Ala Leu Val Met Tyr Leu Leu Lys Leu For Asp Val Glu Lys

195 200 205

Glu Met Lys Glu Thr Thr Gin Lys Ser Leu Phe Ser Hls Lys His

210 215 220

Phe Val Phly Gly Ala Leu Gly Phe Phe Tyr Val Gly Gly Glu Val

(+420) 225 230 235 240

Ala il Gly Ser Phe Leu Val Leu Ser Phe Glu Lys Leu Leu Asn Leu

245

Asp Ala Gin Ser Ser

260 265 270

Met Val Gly 275 Arg Phe Leu Gly Ser Ile Ala for 280 285 same time Lys Tyr Leu Ala Phe same time Ala Leu Ser Ser Ile Ile Leu Ile Ala 290 295 300 Leu Ala Ile Leu Ile Gly Gly Lys Ile Ala Leu Phe Ala Leu Thr Phe 305 310 315 320 wall Gly Phe Phe same time Ser Ile Met Phe for Thr Ile Phe Ser Leu Ala 325 330 335 Thr Leu same time Leu Gly His Leu Thr Ser Lys Ala Ser Gly wall Ile Ser 340 345 350 Met Ala Ile wall Gly Gly Ala Leu Ile for for Ile gin Gly wall wall 355 360 365 Thr Asp Met Leu Thr Ala Thr Glu Ser same time Leu Leu Tyr Ala Tyr Ser 370 375 380 wall for Leu Leu Cys Tyr Phe Tyr Ile Leu Phe Phe Ala Leu Lys Gly 385 390 395 400 Tyr Lys gin Glu Glu same time Ser 405

(2) INFORMATION FOR SEQUENCE NO. 116:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 125 amino acids (B) TYPE: amino acid

249 (D) TOPOLOGY: linear (ii) MOLECULA TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) NAME / KEY: various characters (B) LOCATION 1 ... 125 (xi) SEQUENCE DESCRIPTION: Sequence no. 116:

Met 1 same time Lys Ile Ala 5 for same time Lys Ser Ile Ile Leu 20 Ile Ala Leu Ala Leu Phe Ala 35 Leu Thr Phe wall Gly 40 Thr Ile 50 Phe Ser Leu Ala Thr 55 Leu Ala 65 Ser Gly wall Ile Ser 70 Met Ala for Ile gin Gly wall 85 wall Thr Asp Leu Leu Tyr Ala 100 Tyr Ser wall for Phe Phe Ala 115 Leu Lys Gly Tyr Lys 120

Tyr Leu Ala Phe Gly Ala Leu Ser 10 15 white Leu white Gly Gly Lys white Ala

30

Phe Phe Asn Ser I Met Phe Pro

Asn Leu Gly White Ser Leu Leu Met 60 White Val Gly Gly Ala Leu White Pro 75 80

Met Leu Thr Glu Ser Asn 90 95 95

Leu Leu Cys Tyr Phe Tyr White Leu 105 110

Gin Glu Glu Asn Ser

125 (2) INFORMATION FOR SEQUENCE NO. 117:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 330 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULA TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE:

250 (A) ORGANISM: Helicobacter pylori (ix)

(A) TITLE / KEY: various characters (B) LOCATION 1 ... 330 (xi) SEQUENCE DESCRIPTION: Sequence no. 117:

Leu Lys Lys Ile Leu for Ala Leu Leu Met Gly Phe wall Gly Leu same time 1 5 10 15 Ala Ser Asp Arg Leu Leu Glu Ile Met Arg Leu Tyr gin Lys gin Gly 20 25 30 Leu Glu wall wall Gly gin Lys Leu Asp Ser Tyr Leu Ala Asp Lys Ser 35 40 45 Phe Trp Ala Glu Glu Leu gin same time Lys Asp Thr Asp Phe Gly Tyr Tyr 50 55 60 gin same time Lys gin Phe Leu Phe wall Ala Asp Lys Ser Lys for Ser Leu 65 70 75 80 Glu Phe Tyr Glu Ile Glu same time same time Met Leu Lys Lys Ile same time Ser Ser 85 90 95 Lys Ala Leu wall Gly Ser Lys Lys Gly Asp Lys Thr Leu Glu Gly Asp 100 105 110 Leu Ala Thr for Ile Gly wall Tyr Arg Ile Thr gin Lys Leu Glu Arg 115 120 125 Leu Asp gin Tyr Tyr Gly wall Leu Ala Phe wall Thr same time Tyr for same time 130 135 140 Leu Tyr Asp Thr Leu Lys Lys Arg Thr Gly His Gly Ile Trp wall His 145 150 155 160 Gly Met for Leu same time Gly Asp Arg same time Glu Leu same time Thr Lys Gly Cys 165 170 175 Ile Ala Ile Glu same time for Ile Leu Ser Ser Tyr Asp Lys wall Leu Lys 180 185 190 Gly Glu Lys Ala Phe Leu Ile Thr Tyr Glu Asp Lys Phe Ser for Ser 195 200 205 Thr Lys Glu Glu Leu Ser Met Ile Leu Ser Ser Leu Phe gin Trp Lys 210 215 220 Glu Ala Trp Ala Arg Gly Asp Phe Glu Arg Tyr Met Arg Phe Tyr same time 225 230 235 240 for same time Phe Thr Arg Tyr Asp Gly Met Ser Phe same time Ala Phe Lys Glu 245 250 255 Tyr Lys Lys Arg wall Phe Ala Lys same time Glu Lys Lys same time Ile Ala Phe 260 265 270 Ser Ser Ile same time wall Ile for Tyr for same time Ser gin same time Lys Arg Leu 275 280 285

251

Phe Tyr wall Phe Asp Gin Asp Tyr Lys 290 295 300 Leu Ser Tyr Ser Ser same time Ser gin Lys Glu Leu Tyr wall Glu Ile Glu 305 310 315 320 same time same time gin Ala Ser Ile Ile Met Glu Lys 325 330

(2) INFORMATION FOR SEQUENCE NO. 118:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 169 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULA TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) TITLE / KEY: various characters (B) LOCATION 1 ... 169 (xi) SEQUENCE DESCRIPTION: Sequence no. 118:

Leu Phe Glu Lys Trp Ile Gly Leu Thr Leu Leu Leu Ser Ser Leu Gly 1 5 10 15 Tyr for Cys gin Lys wall Ser Ile Ser Phe Lys gin Tyr Glu same time Leu 20 25 30 Ile His Ile His gin Lys Gly Cys same time same time Glu wall wall Cys Arg Thr 35 40 45 Leu Ile Ser Ile Ala Leu Leu Glu Ser Ser Leu Gly Leu same time same time Lys 50 55 60 Arg Glu Lys Ser Leu Lys Asp Thr Ser Tyr Ser Met Phe His Ile Thr 65 70 75 80 Leu same time Thr Ala Lys Lys Phe Tyr for Thr Tyr Ser Lys Thr Leu Leu 85 90 95 Lys Thr Lys Leu Leu same time Asp wall Gly Phe Ala Ile gin Leu Ala Lys 100 105 110 gin Ile Leu Lys Glu same time Phe Asp Tyr Tyr His gin Lys His for same time 115 120 125 Lys Ser wall Tyr gin Leu wall gin Met Ala Ile Gly Ala Tyr same time Gly

252

129 135 140

Gly Met Lys His Asn For Asn Gly Ala Tyr

165 (2) INFORMATION FOR SEQUENCE NO. 119:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 215 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULA TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) TITLE / KEY: different characters

(B) LOCATION 215 (Xi) SEQUENCE DESCRIPTION: Sequence no. 119: Met Lys Lys for Tyr Arg Lys Ile Ser Asp Tyr Ala Ile wall Gly Gly 1 5 10 15 Leu Ser Ala Leu wall Met wall Ser Ile wall Gly Cys Lys Ser same time Ala 20 25 30 Asp Asp Lys for Lys Glu gin Ser Ser Leu Ser gin Ser wall gin Lys 35 40 45 Gly Ala Phe wall Ile Leu Glu Glu gin Lys Asp Lys Ser Tyr Lys wall 50 55 60 wall Glu Glu Tyr for Ser Ser Arg Thr His Ile wall wall Arg Asp Leu 65 70 75 80 gin Gly same time Glu Arg wall Leu Ser same time Glu Glu Ile gin Lys Leu Ile 85 90 95 Lys Glu Glu Glu Ala Lys Ile Asp same time Gly Thr Ser Lys Leu wall gin 100 105 110 for same time same time Gly Gly Ser same time Glu Gly Ser Gly Phe Gly Leu Gly Ser 115 120 125 Ala Ile Leu Gly Ser Ala Ala Gly Ala Ile Leu Gly Ser Tyr Ile Gly 130 135 140

253

same time Lys Leu Phe same time same time for same time Tyr gin gin same time Ala gin Arg Thr 145 150 155 160 Tyr Lys Ser for gin Ala Tyr gin Arg Ser gin same time Ser Phe Ser Lys 165 170 175 Ser Ala for Ser Ala Ser Ser Met Gly Thr Ala Ser Lys Gly gin Ser 180 185 190 Gly Phe Phe Gly Ser Ser Arg for Thr Ser Ser for Ala Ile Ser Ser 195 200 205 Gly Thr Arg Gly Phe same time Ala 210 215

(2) INFORMATION FOR SEQUENCE no. 120:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 253 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULA TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) NAME / KEY: various characters (B) LOCATION 1 ... 253 (xi) SEQUENCE DESCRIPTION: Sequence no. 120:

Leu Lys Thr Leu Phe Ser wall Tyr Leu Phe Leu Ser Leu same time for Leu 1 5 10 15 Phe Leu Glu Ala Lys Glu Ile Thr Trp Ser gin Phe Leu Glu same time Phe 20 25 30 Lys same time Lys same time Glu Asp Asp Lys for Lys for Leu Thr Ile Asp Lys 35 40 45 same time same time Glu Lys gin gin Ile Leu Asp Lys same time gin gin Ile Leu Lys 50 55 60 Arg Ala Leu Glu Lys Ser Leu Lys Phe Phe Phe Ile Phe Gly Tyr same time 65 70 75 80 Tyr Ser gin Ala Ala Tyr Ser Thr Thr same time gin same time Leu Thr Leu Thr 85 90 95 Ala same time Ser Ile Gly Phe same time Thr Ala Thr Gly Leu Glu His Phe Leu

254

100

Arg same time His 115 for Lys wall Gly Phe 120 Phe His 130 Ser wall Ser Leu Ser 135 gin Tyr 145 Gly Gly Ala Leu Asp 150 Phe Ser Tyr Arg Phe Arg Ser 165 Tyr Leu Gly Leu wall Asp Thr 180 Ile Lys Thr Gly Thr Lys Lys 195 Thr Phe Phe gin Ala 200 Asp Phe 210 Ile Gly Tyr Leu Ser 215 Leu wall 225 Arg same time wall Phe Tyr 230 Thr Tyr for Arg Phe same time Ala 245 same time Leu Ser

105 Arg Ile Phe Ser wall 110 Tyr same time Tyr for gin Ile Leu 125 Met wall gin same time Trp Ile Phe 140 wall Asp Lys Lys Thr Ile Ala 155 Leu Glu gin Gly wall 160 Leu Ser 170 Phe Thr Thr Ile Ile 175 for Arg 185 for Leu Arg Phe Gly 190 Phe Ile wall gin Leu Gly Ile 205 Glu Met for Leu same time same time His 220 gin Glu Arg Phe Lys Leu Ile 235 wall Ser Phe 240

250 (2) INFORMATION FOR SEQUENCE NO.

(I)

121:

SEQUENCE CHARACTERISTICS:

(A) LENGTH:

(B) (ii) (iii) (vi) (ix) (xi)

336 amino acids TYPE: amino acid (D) TOPOLOGY: linear

MOLECULA TYPE: protein

HYPOTHETICAL: YES

ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori

SIGN:

(A) TITLE / KEY: different characters (B) LOCATION 1 ... 336

SEQUENCE DESCRIPTION: Seq. 121:

Leu Phe Phe Lys Phe Leu Cys Leu Ser Leu Gly Ile Phe Ala Trp 1 5 10 15 Ala Lys Glu Val Ile Pro Thr Pro Ser Thr Pro Leu Thr Pro Ser Lys 20 25 30

255

Arg Tyr Ser 35 Asn Leu Met Thr Glu Asn Asp Gly Tyr Asn Pro 40 45 Tyr Ile Asp Glu Tyr Tyr Thr Ala Gly same time gin Ile Gly Phe Ser Thr 50 55 60 Lys Glu Phe Asp Phe Ser Lys same time Lys Ala Met Lys Trp Ser Ser Tyr 65 70 75 80 Leu Gly Phe Phe same time Lys Ser for Arg wall Thr Arg Phe Gly Ile Ser 85 90 95 Leu Ala gin Asp Met Tyr Thr for Ser Leu Ala same time Arg Lys Leu wall 100 105 110 His Leu His Asp same time His for Tyr Gly Gly Tyr Leu Arg wall same time Leu 115 120 125 same time wall Tyr same time Arg His gin Thr Phe Met Glu Leu Phe Thr Ile Ser 130 135 140 Leu Gly Thr Thr Gly gin Asp Ser Leu Ala Ala gin Thr gin Arg Leu 145 150 155 160 Ile His Lys Trp Gly His Asp for gin Phe Tyr Gly Trp same time Thr gin 165 170 175 Leu Lys same time Glu Phe Ile Phe Glu Leu His Tyr gin Leu Leu Lys Lys 180 185 190 wall for Leu Leu Lys Thr Arg Phe Phe Ser Met Glu Leu Met for Gly 195 200 205 Phe same time wall Glu Leu Gly same time Ala Arg Asp Tyr Phe gin Leu Gly Ser 210 215 220 Leu Phe Arg Ala Gly Tyr same time Leu Asp Ala Asp Tyr Gly wall same time Lys 225 230 235 240 wall same time Thr Ala Phe Asp Gly Gly Met for Tyr Ser Asp Lys Phe Ser 245 250 255 Ile Tyr Phe Phe Ala Gly Ala Phe Gly Arg Phe gin for Leu same time Ile 260 265 270 Phe Ile gin Gly same time Ser for Glu Thr Arg Gly Ile Ala same time Leu Glu 275 280 285 Tyr Phe wall Tyr Ala Ser Glu Ile Gly Ala Ala Met Met Trp Arg Ser 290 295 300 Leu Arg wall Ala Phe Thr Ile Thr Asp Ile Ser Lys Thr Phe gin Ser 305 310 315 320 gin for Lys His His gin Ile Gly Thr Leu Glu Leu same time Phe Ala Phe 325 330 335

(2) INFORMATION FOR SEQUENCE NO. 122:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 108 amino acids (B) TYPE: amino acid

256 (D) TOPOLOGY: linear (ii) MOLECULA TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix) SIGN (A) NAME / KEY: different characters (B) PLACEMENT 1 ... 108

(xi) SEQUENCE DESCRIPTION: Sequence £. 122:

Met 1 Lys Pro Phe Ser Leu Phe Phe Leu Leu Val Leu Lys Ala 5 10 15 His for Ile same time for Leu Leu Glu for Leu Tyr Phe for Ser Tyr Thr 20 25 30 gin Phe Leu Asp Leu Glu for His Phe wall Ile Lys Lys Lys Arg Ala 35 40 45 Tyr Arg for Phe gin Trp Gly same time Thr Ile Ile Ile Lys Arg His Asp 50 55 60 Leu Glu Glu Arg gin Ser same time gin for Ser Asp Ile Phe Arg gin same time 65 70 75 80

Ala Glu Asn wall 85 Ser Ser Gin Thr Phe 90 Leu Arg Gly White Ser Ser 95 Ala Ser Ser Arg Ile wall Ile Asp Ser wall Ala gin 100 105

(2) INFORMATION FOR SEQUENCE NO. 123:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 195 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULA TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori

257 (ix) SIGN:

(A) NAME / KEY: various characters (B) LOCATION 1 ... 195 (xi) SEQUENCE DESCRIPTION: Sequence £. 123:

Met 1 Ser Asn Asn for 5 Phe Lys Lys Val Gly Met 10 Ser Ser gin 15 same time same time same time Gly Ala Leu same time Gly Leu Gly wall gin wall Gly Tyr Lys gin 20 25 30 Phe Phe Gly Glu Ser Lys Arg Trp Gly Leu Arg Tyr Tyr Gly Phe Phe 35 40 45 Asp Tyr same time His Gly Tyr Ile Lys Ser Ser Phe Phe same time Ser Ser Ser 50 55 60 Asp Ile Trp Thr Tyr Gly Gly Gly Ser Asp Leu Leu wall same time Phe Ile 65 70 75 80 same time Asp Ser Ile Thr Arg Lys same time same time Lys Leu Ser wall Gly Leu Phe 85 90 95 Gly Gly Ile gin Leu Ala Gly Thr Thr Trp Leu same time Ser gin Tyr Met 100 105 110 same time Leu Thr Ala Phe same time same time for Tyr Ser Ala Lys wall same time Ala Ser 115 120 125 same time Phe gin Phe Leu Phe same time Leu Gly Leu Arg Thr same time Leu Ala Thr 130 135 140 Ala Lys Lys Lys Asp Ser Glu Arg Ser Ala gin His Gly wall Glu Leu 145 150 155 160 Gly Ile Lys Ile for Thr Ile same time Thr same time Tyr Tyr Ser Phe Leu Gly 165 170 175 Thr Lys Leu Glu Tyr Arg Arg Leu Tyr Ser wall Tyr Leu same time Tyr wall 180 185 190 Phe Ala Tyr

195 (2) INFORMATION FOR SEQUENCE NO. 124:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 227 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULA TYPE: protein (iii) HYPOTHETICAL: YES

258 (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (Ix) SIGN: (A) TITLE / KEY: different characters (B, LOCATION 1 ... 227 (Xi) SEQUENCE DESCRIPTION: Seq. 124:

wall Arg Phe Gly Lys Ile Asp Tyr Leu same time Met Leu for Phe Asp wall 1 5 10 15 Phe Ile Lys Ser Tyr for Thr for Cys Tyr Phe Lys gin Phe Leu Arg 20 25 30 Leu Lys Lys Thr Tyr for Ser Lys Leu same time Glu Ser Phe Leu Phe Arg 35 40 45 Arg Ile Asp Ala Gly Phe Ile Ser Ser Ile Ala Gly Tyr for Phe Ala 50 55 60 Leu Cys Ser Tyr Ser Leu Gly Ile wall Ala Tyr Lys Glu wall Leu Ser 65 70 75 80 wall Leu wall wall same time Arg Glu same time Ala Phe Asp Lys Glu Ser Ala Ser 85 90 95 Ser same time Ala Leu Ser Lys wall Leu Gly Leu Lys Gly Glu wall Leu Ile 100 105 110 Gly same time Lys Ala Leu gin Phe Tyr Tyr Ser same time for Lys Lys Asp Phe 115 120 125 Ile Asp Leu Ala Ala Leu Trp Tyr Glu Lys Lys Arg Leu for Phe wall 130 135 140 Phe Gly Arg Leu Cys Tyr Tyr gin same time Lys Asp Phe Tyr Lys Arg Leu 145 150 155 160 Ser Leu Ala Phe Lys His gin Lys Thr Lys Ile for His Tyr Ile Leu 165 170 175 Lys Glu Ala Ala Leu Lys Thr same time Leu Lys Arg gin Asp Ile Leu same time 180 185 190 Tyr Leu gin Lys Ile Tyr Tyr Thr Leu Gly Lys Lys Glu gin Ser Gly 195 200 205 Leu Lys Ala Phe Tyr Arg Glu Leu Leu Phe Lys Arg Ile gin Lys for 210 215 220 Lys Arg Phe

225 (2) INFORMATION FOR SEQUENCE NO. 125:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 305 amino acids

259 (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULA TYPE: protein (iii) HYPOTHETICAL: YES (vi, ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) TITLE / KEY: various characters (B) LOCATION 1 ... 305 (xi) SEQUENCE DESCRIPTION: Sequence no. 125:

Met 1 Gly Arg Ile Glu 5 Ser Lys Lys Ala Ser Leu Gly 20 wall Leu Trp Gly Phe Lys Thr 35 Lys same time His Ile Tyr 40 Ala Thr 50 Thr Arg Thr Ser Met 55 Trp Thr 65 Cys for Ser Ser wall 70 Cys Tyr Lys Gly Gly Lys same time 85 Leu Ser Tyr Ala Phe Asp Lys 100 Tyr His Ile Leu Glu Tyr Ala 115 Lys Ala gin Leu Gly 120 Leu Ser 130 gin Ala same time Tyr same time 135 for Thr 145 Ser same time Ala gin Gly 150 Ser Leu gin Asp Phe Leu Phe 165 same time same time Gly wall same time Met Phe 180 wall same time Leu for Leu Lys Thr 195 Glu Lys Met Leu Phe 200 Gly Gly 210 wall Glu Tyr Ala Ile 215 Leu

Arg Leu 10 Lys Ala Leu Ile Phe 15 Leu same time 25 Ala Ala Glu Lys Thr 30 for Phe Leu Gly Phe Arg Leu 45 Gly Thr Gly gin gin Ala Tyr 60 Lys Asp same time for Gly Glu Lys 75 Leu Glu Ala His Tyr 80 Thr Gly 90 gin Ile Gly Asp Glu 95 Ile Gly 105 Leu Arg wall Trp Gly 110 Asp wall gin Lys wall Gly Gly 125 same time Thr Leu Ser Ala Ile Lys 140 Thr Tyr Asp for wall Leu gin 155 Lys Thr for Ser for 160 His Phe 170 Met Ala Phe Gly Leu 175 same time Ile 185 Asp Thr Leu Leu Lys 190 Leu Ala Phe Lys Ile Gly wall 205 Phe Gly Gly Trp Ser for gin 220 Tyr Lys same time gin

260

same time Thr His gin Asp Asp Lys Phe Phe Ala Ala Gly Gly Gly Phe Phe 225 230 235 240 wall same time Phe Gly Gly Ser Leu Tyr Ile Gly Lys Arg same time Arg Phe same time 245 250 255 wall Gly Leu Lys Ile for Tyr Tyr Ser Leu Ser Ala gin Ser Trp Lys 260 265 270 same time Phe Gly Ser Ser same time wall Trp gin gin gin Thr Ile Arg gin same time 275 280 285 Phe Ser wall Phe Arg same time Lys Glu wall Phe wall Ser Tyr Ala Phe Leu 290 295 300 Phe 305 (2) INFORMATION FOR SEQUENCE NO. 126:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 258 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULA TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix) SIGN (A) NAME / KEY: different characters (B) PLACEMENT 1 ... 258

(xi) SEQUENCE DESCRIPTION: SEQ ID NO. 126:

Met Phe Leu Arg Ser Tyr for Lys Leu Arg Tyr Ala Leu Cys Leu for 1 5 10 15 Leu Leu Thr Glu Thr Cys Tyr Ser Glu Glu Arg Thr Leu same time Lys wall 20 25 30 Thr Thr gin Ala Lys Arg Ile Phe Thr Tyr same time same time Glu Phe Lys wall 35 40 45 Thr Ser Lys Glu Leu Asp gin Arg gin Ser same time Glu wall Lys Asp Leu 50 55 60 Phe Arg Thr same time for Asp wall same time wall Gly Gly Gly Ser wall Met Gly 65 70 75 80 gin Lys Ile Tyr wall Arg Gly Ile Glu Asp Arg Leu Leu Arg wall Thr

261

85 90 95 Val Asp Gly Ala Ala Gin Asn Gly Asn White Tyr His His Gin Gly Asn 100 105 110 Thr Val White Asp Pro Gly Met Leu Lys Ser Glu Val Thr Lys Gly 115 120 125 Ala Ala Asn Ala Ser Ala Gly Pro Gly Ala Ala Ala Gly Val Lys 130 135 140 Met Glu Thr Lys Gly Ala Ala Asp Phe White Pro Arg Gly Lys Asn Tyr 145 150 155 160 Ala Ala Gly Ala Val Ser Phe Tyr Thr Asn Phe Gly Asp Arg Glu 165 170 175 Thr Phe Arg Ala Tyr Gin Ser Ala His Phe Asp White Ala Tyr 180 185 190 Tyr Thr His Gin Asn ile Phe Tyr Tyr Arg Gly Ala Thr Val Met 195 200 205 Lys Asn Leu Phe Lys Pro Thr Gin Ala Lys Glu Pro Gly Thr Pro 210 215 220 Ser Glu Gin Asn Asn Ala Leu White Lys Met Asn Gly Tyr Leu Ser Asp 225 230 235 240 Arg Asp Thr Leu Thr Phe Ser Asp Met Thr Arg Asp Asn Ala Thr 245 250 255 Arg Leu (2) INFORMATION FOR SEQUENCE NO. 127: (i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 192 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULA TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) TITLE / KEY: various characters (B) LOCATION 1 ... 192 (xi) SEQUENCE DESCRIPTION: Seq. 127:

262

Met Phe Leu Arg Ser Tyr for Lys Leu Arg Tyr Ala Leu Cys Leu for 1 5 10 15 Leu Leu Thr Glu Thr Cys Tyr Ser Glu Glu Arg Thr Leu same time Lys wall 20 25 30 Thr Thr gin Ala Lys Arg Ile Phe Thr Tyr same time same time Glu Phe Lys wall 35 40 45 Thr Ser Lys Glu Leu Asp gin Arg gin Ser same time Glu wall Lys Asp Leu 50 55 60 Phe Arg Thr same time for Asp wall same time wall Gly Gly Gly Ser wall Met Gly 65 70 75 80 gin Lys Ile Tyr wall Arg Gly Ile Glu Asp Arg Leu Leu Arg wall Thr 85 90 95 wall Asp Gly Ala Ala gin same time Gly same time Ile Tyr His His gin Gly same time 100 105 110 Thr wall Ile Asp for Gly Met Leu Lys Ser wall Glu wall Thr Lys Gly 115 120 125 Ala Ala same time Ala Ser Ala Gly for Gly Ala Ile Ala Gly wall Ile Lys 130 135 140 Met Glu Thr Lys Gly Ala Ala Asp Phe Ile for Arg Gly Lys same time Tyr 145 150 155 160 Ala Ala Ser Gly Ala wall Ser Phe Tyr Thr same time Phe Gly Asp Arg Glu 165 170 175 Thr Phe Arg Ser Ala Tyr gin Ser Ala His Phe Asp Ile Ile Ala Tyr 180 185 190

(2) INFORMATION FOR SEQUENCE NO. 128:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 126 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULA TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix) SIGN (A) NAME / KEY: different characters (B) PLACEMENT 1 ... 126

(xi) SEQUENCE DESCRIPTION: SEQ ID NO. 128:

263

wall for Leu Ser Leu Gly Gly same time Leu Leu same time for same time same time Ser Ser 1 5 10 15 wall Leu same time Leu Lys same time Ser gin Leu wall Phe Ser Asp gin Gly Ser 20 25 30 Leu same time Ile Ala same time Ile Asp Leu Leu Ser Asp Leu same time Gly same time Lys 35 40 45 same time Arg wall Tyr same time Ile Ile gin Ala Asp Met same time Gly same time Trp Tyr 50 55 60 Glu Arg Ile same time Phe Phe Gly Met Arg Ile same time Asp Gly Ile Tyr Asp 65 70 75 80 Ala Lys same time gin Thr Tyr Ser Phe Thr same time for Leu same time same time Ala wall 85 90 95 Lys Phe Thr Glu Ser Phe Phe Ile His Arg Leu Cys Gly Ser Leu Ser 100 105 110 gin Ile gin Lys Lys Lys same time Thr Ile wall Ser for Arg Leu 115 120 125 (2) INFORMATION FOR SEQUENCE NO. 129:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 565 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULA TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) NAME / KEY: various characters (B) LOCATION 1 ... 565 (xi) SEQUENCE DESCRIPTION: Sequence no. 129:

wall Tyr Ser Tyr Ser Asp Asp Ala gin Gly wall Phe Tyr Leu Thr Ser 1 5 10 15 Ser wall Lys Gly Tyr Tyr same time for same time gin Ser Tyr gin Ala Ser Gly 20 25 30 Ser same time same time Thr Thr Lys same time same time same time Leu Thr Ser Glu Ser Ser wall 35 40 45

264

Ile Ser gin Thr Tyr same time Ala gin Gly same time for Ile Ser Ala Leu His 50 55 60 wall Tyr same time Lys Gly Tyr same time Phe Ser same time Ile Lys Ala Leu Gly gin 65 70 75 80 Met Ala Leu Lys Leu Tyr for Glu Ile Lys Lys Ile Leu Gly same time Asp 85 90 95 Phe Ser Leu Ser Ser Leu Ser same time Leu Lys Gly Asp Ala Leu same time gin 100 105 110 Leu Thr Lys Leu Ile Thr for Ser Asp Trp Lys same time Ile same time Glu Leu 115 120 125 Ile Asp same time Ala same time same time Ser wall wall gin same time Phe same time same time Gly Thr 130 135 140 Leu Ile Ile Gly Ala Thr Lys Ile Gly gin Thr Asp Thr same time Ser Ala 145 150 155 160 wall wall Phe Gly Gly Leu Gly Tyr gin Lys for Cys Asp Tyr Thr Asp 165 170 175 Ile wall Cys gin Lys Phe Arg Gly Thr Tyr Leu Gly gin Leu Leu Glu 180 185 190 Ser same time Ser Ala Asp Leu Gly Tyr Ile Asp Thr Thr Phe same time Ala Lys 195 200 205 Glu Ile Tyr Leu Thr Gly Thr Leu Gly Ser Gly same time Ala Trp Gly Thr 210 215 220 Gly Gly Ser Ala Ser wall Thr Phe same time Ser gin Thr Ser Leu Ile Leu 225 230 235 240 same time gin Ala same time Ile wall Ser Ser gin Thr Asp Gly Ile Phe Ser Met 245 250 255 Leu Gly gin Glu Gly Ile same time Lys wall Phe same time gin Ala Gly Leu Ala 260 265 270 same time Ile Leu Gly Glu wall Ala Met gin Ser Ile same time Lys Ala Gly Gly 275 280 285 Leu Gly same time Leu Ile wall same time Thr Leu Gly Ser Asp Ser wall Ile Gly 290 295 300 Gly Tyr Leu Thr for Glu gin Lys same time gin Thr Leu Ser gin Leu Leu 305 310 315 320 Gly gin same time same time Phe Asp same time Leu Met same time Asp Ser Gly Leu same time Thr 325 330 335 Ala Ile Lys Asp Leu Ile Arg gin Lys Leu Gly Phe Trp Thr Gly Leu 340 345 350 wall Gly Gly Leu Ala Gly Leu Gly Gly Ile Asp Leu gin same time for Glu 355 360 365 Lys Leu Ile Gly Ser Met Ser Ile same time Asp Leu Leu Ser Lys Lys Gly 370 375 380 Leu Phe same time gin Ile Thr Gly Phe Ile Ser Ala same time Asp Ile Gly gin

385

390

395

400

265

wall Ile Ser Val Met 405 Leu Gin Asp Ile Val Lys 410 Pro Ser Asp Ala Leu 415 Lys same time Asp wall Ala Ala Leu Gly Lys gin Met Ile Gly Glu Phe Leu 420 425 430 Gly gin Asp Thr Leu same time Ser Leu Glu Ser Leu Leu gin same time gin gin 435 440 445 Ile Lys Ser wall Leu Asp Lys wall Leu Ala Ala Lys Gly Leu Gly Ser 450 455 460 Ile Tyr Glu gin Gly Leu Gly Asp Leu Ile for same time Leu Gly Lys Lys 465 470 475 480 Gly Ile Phe Ala for Tyr Gly Leu Ser gin wall Trp gin Lys Gly Asp 485 4 90 495 Phe Ser Phe same time Ala gin Gly same time wall Phe wall gin same time Ser Thr Phe 500 505 510 Ser same time Ala same time Gly Gly Thr Leu Ser Phe same time Ala Gly same time Ser Leu 515 520 525 Ile Phe Ala Gly same time same time His Ile Ala Phe Thr same time His Ser Gly Thr 530 535 540 Leu same time Leu Leu Ser same time gin wall Ser same time Ile same time wall Thr Met Leu 545 550 555 560 same time Ala Ala Thr Ala

565 (2) INFORMATION FOR SEQUENCE NO. 130:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 172 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULA TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (Ix) SIGN: (A) NAME / KEY: different characters (B) PLACEMENT 1 ... 172 (Xi) DESCRIPTION i SEQUENCES: SEQ ID NO. 130:

Val Phe Gly Leu Ser Leu Ala Asp Met leu Glu Arg Phe Lys Asp

266

10 15

Phe Met Arg Glu Tyr Pro Glu Pro Tyr Lys 25 Phe Leu Gin wall 30 Phe Tyr 20 Ala gin Glu Lys Glu Arg Phe Leu same time His Lys Met same time Asp Tyr Ile 35 40 45 Lys gin same time Lys Ser Lys Glu Glu Ala Ser Ile Leu Ala Arg gin Gly 50 55 60 Phe wall Ser wall Ile Gly Arg Ala Leu Glu Lys Ile Ile Glu Leu Leu 65 70 75 80 Leu Lys Asp Phe Cys Ile Lys same time same time wall Lys Met Thr same time Asp Lys 85 90 95 Thr Leu Arg Ala Lys Arg Ile same time Gly Glu Leu Asp Lys wall Lys Arg 100 105 110 Ala Leu Leu wall His Phe Gly Gly Tyr Ser wall Leu for Asp Ile Ile 115 120 125 Leu Tyr gin Thr same time Lys Asp same time Ile Lys Ile Leu Ala Ile Leu Ser 130 135 140 wall Lys same time Ser Phe Arg Glu Arg Phe Thr Lys Asp Ala Leu Leu Glu 145 150 155 160 Ile Lys Thr Phe Ala Ile Ala Cys same time Phe Ser His

165 170 (2) INFORMATION FOR SEQUENCE NO. 131:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 331 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULA TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) TITLE / KEY: various characters (B) LOCATION 1 ... 331

(Xi) DESCRIPTION SEQUENCE: Sequence no. 131: Met Lys Arg Phe Val Leu Phe Cys Val Cys 1 5 10 15

267

wall gin Ala Tyr Ala 20 Glu Gin Asp Tyr Phe Phe Arg 25 30 Ile Asp Leu for gin Lys Leu His Leu Asp Lys Lys Leu Ser gin Thr 35 40 45 Ile gin for Cys Ala gin Leu same time Ala Ser Lys His Tyr Thr Ala Thr 50 55 60 Gly wall Arg Glu for Asp Ala Cys Thr Lys Ser Phe Lys Lys Ser Ala 65 70 75 80 Met wall Ser Tyr Asp Leu Ala Leu Gly Tyr Leu wall Ser gin same time Lys 85 90 95 for Tyr Gly Leu Lys Ala Ile Glu Ile Leu same time Ala Trp Ala same time Glu 100 105 110 Leu gin Ser wall Asp Thr Tyr gin Ser Glu Asp same time Ile same time Phe Tyr 115 120 125 Met for Tyr Met same time Met Ala Tyr Trp Phe wall Lys Lys Glu Phe for 130 135 140 Ser for Glu Tyr Glu Asp Phe Ile Arg Arg Met Arg gin Tyr Ser gin 145 150 155 160 Ser Ala Leu same time Thr same time His Gly Ala Trp Gly Ile Leu Phe Asp wall 165 170 175 Ser Ser Ala Leu Ala Leu Asp Asp His Ala Leu Leu gin Ser Ser Ala 180 185 190 same time Arg Trp gin Glu Trp wall Phe Lys Ala Ile Asp Glu same time Gly wall 195 200 205 Ile Ala Ser Ala Ile Thr Arg Ser Asp Thr Ser Asp Tyr His Gly Gly 210 215 220 for Thr Lys Gly Ile Lys Gly Ile Ala Tyr Thr same time Phe Ala Leu Leu 225 230 235 240 Ala Ile Thr Ile Ser Gly Glu Leu Leu Phe Glu same time Gly Tyr Asp Leu 245 250 255 Trp Gly Ser Gly Ala Gly gin Arg Leu Ser wall Ala Tyr same time Lys Ala 260 265 270 Ala Thr Trp Ile Leu same time for Glu Thr Phe for Tyr Phe gin for same time 275 280 285 Leu Ile Gly wall His same time same time Ala Tyr Phe Ile Ile Leu Ala Lys His 290 295 300 Tyr Ser Ser for Ser Ala Asp Glu Leu Leu Glu gin Gly Asp Leu His 305 310 315 320 Glu Asp Gly Phe Arg Leu Lys Leu Arg Ser for

325 330 (2) INFORMATION FOR SEQUENCE NO. 132:

(i) SEQUENCE CHARACTERISTICS:

268 (A) LENGTH: 128 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULA TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix) SIGN: (A) NAME / KEY: different characters (B) PLACEMENT 1 ... 128

(xi) SEQUENCE DESCRIPTION: SEQ ID NO. 132:

Met Arg gin Tyr Ser gin Ser Ala Leu same time Thr same time His Gly Ala Trp 1 5 10 15 Gly Ile Leu Phe Asp wall Ser Ser Ala Leu Ala Leu Asp Asp His Ala 20 25 30 Leu Leu gin Ser Ser Ala same time Arg Trp gin Glu Trp wall Phe Lys Ala 35 40 45 Ile Asp Glu same time Gly wall Ile Ala Ser Ala Ile Thr Arg Ser Asp Thr 50 55 60 Ser Asp Tyr His Gly Gly for Thr Lys Gly Ile Lys Gly Ile Ala Tyr 65 70 75 80 Thr same time Phe Ala Leu Leu Ala Ile Thr Ile Ser Gly Glu Leu Leu Phe 85 90 95 Glu same time Gly Tyr Asp Leu Trp Gly Ser Gly Ala Gly gin Arg Leu Ser 100 105 110 wall Ala Tyr same time Lys Ala Ala Thr Trp Ile Leu same time for Glu Thr Phe 115 120 125

(2) INFORMATION FOR SEQUENCE NO. 133:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 245 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULA TYPE: protein (iii) HYPOTHETICAL: YES

269 (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix) SIGN (A) NAME / KEY: different characters (B) PLACEMENT 1 ... 245

(xi) SEQUENCE DESCRIPTION: SEQ ID NO. 133:

Leu Arg Thr Leu Leu Lys Met Leu Val Gly Val Ser Leu Le Thr His 1 5 10 15 Ala Leu Met Ala Thr Glu Glu Ser Ala Ala for Ser Trp Thr Lys same time 20 25 30 Leu Tyr Met Gly Phe same time Tyr gin Thr Gly Ser Ile same time Leu Met Thr 35 40 45 same time Ile His Glu wall Arg Glu wall Thr Ser Tyr gin Thr Gly Tyr Thr 50 55 60 same time wall Met Thr Ser Ile same time Ser wall Lys Lys Leu Thr same time Met Gly 65 70 75 80 Ser same time Gly Ile Gly Leu wall Met Gly Tyr same time His Phe Phe His for 85 90 95 Asp Lys wall Leu Gly Leu Arg Tyr Phe Ala Phe Leu Asp Trp gin Gly 100 105 110 Tyr Gly Met Arg Tyr for Lys Gly Tyr Tyr Gly Gly same time same time Met Ile 115 120 125 Thr Tyr Gly wall Gly wall Asp Ala Ile Trp same time Phe Phe gin Gly Ser 130 135 140 Phe Tyr gin Asp Asp Ile Gly wall Asp Ile Gly wall Phe Gly Gly Ile 145 150 155 160 Ala Ile Ala Gly same time Ser Trp Tyr Ile Gly same time Lys Gly gin Glu Leu 165 170 175 Leu Gly Ile Thr same time Ser Ser Ala wall Asp same time Thr Ser Phe gin Phe 180 185 190 Leu Phe same time Phe Gly Phe Lys Ala Leu Phe wall Asp Glu His Glu Phe 195 200 205 Glu Ile Gly Phe Lys Phe for Thr Leu same time same time Lys Tyr Tyr Thr Thr 210 215 220 Asp Ala Leu Lys wall gin Met Arg Ärg wall Phe Ala Phe Tyr wall Gly 225 230 235 240 Tyr same time Tyr His Phe 245

(2) INFORMATION FOR SEQUENCE NO. 134:

270 (i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 290 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULA TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) NAME / KEY: various characters (B) LOCATION 1 ... 290 (xi) SEQUENCE DESCRIPTION: Sequence £. 134:

Met Phe Glu Glu Ile Thr Leu Ala 1 Leu gin Thr gin 5 Lys Ile wall Leu Phe Leu Trp 20 gin His Ala Arg Leu Cys Leu 35 wall Ile gin Thr Thr 40 Tyr Tyr 50 for Ile Gly Lys Arg 55 for His 65 Leu Glu Lys same time Leu 70 Arg Phe His Asp Leu Lys Asp 85 same time Phe wall Gly Asp Arg Ser 100 Asp Tyr wall Tyr Ser Gly Lys 115 Lys Tyr His Lys Lys 120 Lys same time 130 His Ala same time Phe wall 135 Tyr Glu 145 Glu wall Leu Glu Ala 150 Ser Lys Ala Asp Ile Gly Leu 165 Ile same time Glu same time same time Tyr Glu 180 Ser Leu Asp Leu Lys

His Lys 10 Asp Leu Phe Ser Arg 15 Phe Ser 25 Asp wall Ser Phe Thr 30 same time Cys Ile gin wall Ala wall 45 Ile Arg Asp Glu same time gin Lys 60 for Phe Tyr Phe Glu Cys wall 75 Lys Glu Leu Leu Glu 80 Ser Leu 90 Thr Leu Glu gin Lys 95 Asp wall 105 Phe Asp Phe Thr Tyr 110 same time Arg Ile Glu Glu Leu Ile 125 Ala Leu Lys same time His Leu same time 140 gin Phe Leu Thr Lys Ile Ser 155 for gin same time Arg Lys 160 Trp Phe 170 Leu Glu Ser gin Thr 175 Asp Lys 185 Gly Ile gin Ser wall 190 Leu Glu Gly Gly Leu Ile Arg wall same time Gly

271

195 200 205 Glu Ile wall Ser Phe Ser Phe Gly Glu wall Leu same time Glu Glu Ser Ala 210 215 220 Leu Ile His Ile Glu Lys Ala Arg Thr Asp Ile Ala Gly Ala Tyr gin 225 230 235 240 Ile Ile same time gin gin Leu Leu Leu same time Glu Phe Ser His Leu Thr Tyr 245 250 255 Ala same time Arg Glu Glu Asp Leu Gly Leu Glu Gly Leu Arg Arg Ser Lys 260 265 270 Met Ser Tyr same time for wall Phe Leu Ile Asp Lys Tyr Glu Ala wall Ala 275 280 285 Arg same time 290

(2) INFORMATION FOR SEQUENCE NO. 135:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 110 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULA TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) TITLE / KEY: various characters (B) LOCATION 1 ... 110 (xi) SEQUENCE DESCRIPTION: Sequence no. 135:

Met Met Phe Ile wall Ala wall Leu Met Leu Ala Phe Leu Ile Phe wall 1 5 10 15 His Glu Leu Gly His Phe Ile Ile Ala Arg Ile Cys Gly wall Lys wall 20 25 30 Glu wall Phe Ser Ile Gly Phe Gly Lys Lys Leu Trp Phe Phe Lys Leu 35 40 45 Phe Gly Thr gin Phe Ala Leu Ser Leu Ile for Leu Gly Gly Tyr wall 50 55 60 Lys Leu Lys Gly Met Asp Lys Glu Glu same time Glu Glu same time Lys Ile same time 65 70 75 80

272

gin Ala Asn Asp Ser Tyr Ala Lys Lys Ala Leu Ser Lys Ser Tyr Gly 85 90 95 Tyr Leu Val Gly Arg Leu Ile Phe Phe Leu Arg Phe 100 105 110 (2) INFORMATION j FOR SEQUENCE NO. 136

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 351 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULA TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix) SIGN (A, NAME / KEY: different characters (B) PLACEMENT 1 ... 351

(xi) SEQUENCE DESCRIPTION: SEQ ID NO. 136:

Met Met Phe Ile wall Ala wall Leu Met Leu Ala Phe Leu Ile Phe wall 1 5 10 15 His Glu Leu Gly His Phe Ile Ile Ala Arg Ile Cys Gly wall Lys wall 20 25 30 Glu wall Phe Ser Ile Gly Phe Gly Lys Lys Leu Trp Phe Phe Lys Leu 35 40 45 Phe Gly Thr gin Phe Ala Leu Ser Leu Ile for Leu Gly Gly Tyr wall 50 55 60 Lys Leu Lys Gly Met Asp Lys Glu Glu same time Glu Glu same time Lys Ile same time 65 70 75 80 gin Ala same time Asp Ser Tyr Ala gin Lys Ser for Phe gin Lys Leu Trp 85 90 95 Ile Leu Phe Gly Gly Ala Phe Phe same time Phe Leu Phe Ala wall Leu wall 100 105 110 Tyr Phe Phe Leu Ala Leu Ser Gly Glu Lys wall Leu Leu for wall Ile 115 120 125 Gly Gly Leu Glu Lys same time Ala Leu Glu Ala Gly Leu Leu Lys Gly Asp 130 135 140 Arg Ile Leu Ser Ile same time His gin Lys Ile Ala Ser Phe Arg Glu Ile

273

145 150 155 160

Arg Glu Val Val Ala Arg Ser Gin Gly Glu Leu White Leu Glu White Glu 165 170 175 Arg same time same time gin Ile Leu Glu Lys Arg Leu Thr for Lys Ile wall Ala 180 185 190 wall Ile Ser Glu Ser same time Asp for same time Glu Ile Ile Lys Tyr Lys Ile 195 200 205 Ile Gly Ile Lys for Asp Met gin Lys Met Gly wall wall Ser Tyr Ser 210 215 220 wall Phe gin Ala Phe Glu Lys Ala Leu Ser Arg Phe Lys Glu Gly wall 225 230 235 240 wall Leu Ile wall Asp Ser Leu Arg Arg Leu Ile Met Gly Ser Ala Ser 245 250 255 wall Lys Glu Leu Ser Gly wall Ile Gly Ile wall Gly Ala Leu Ser His 260 265 270 Ala same time Ser wall Ser Met Leu Leu Leu Phe Gly Ala Phe Leu Ser Ile 275 280 285 same time Leu Gly Ile Leu same time Leu Leu for Ile for Ala Leu Asp Gly Ala 290 295 300 gin Met Leu Gly wall wall Phe Lys same time Ile Phe His Ile Ala Leu for 305 310 315 320 Thr for Ile gin same time Ala Leu Trp Leu wall Gly wall Gly Phe Leu wall 325 330 335 Phe wall Met Phe Leu Gly Leu Phe same time Asp Ile Thr Arg Leu Leu

340 345 350 (2) INFORMATION FOR SEQUENCE NO. 137:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 100 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULA TYPE: protein (iii) HYPOTHETICAL: YES (vi, ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) TITLE / KEY: various characters (B, LOCATION 1 ... 100

274 (xi) SEQUENCE DESCRIPTION: SEQ ID NO. 137:

Met gin Lys same time Leu Asp Ser Leu Leu Glu same time Leu Arg Ala Glu Ile 1 5 10 15 Asp Ala Leu Asp same time Glu Leu Ser Asp Leu Leu Asp Lys Arg Leu Gly 20 25 30 Ile Ala Leu Lys Ile Ala Leu Ile Lys gin Glu Ser for gin Glu same time 35 40 45 for Ile Tyr Cys for Lys Arg Glu gin Glu Ile Leu Lys Arg Leu Ser 50 55 60 gin Arg Gly Phe Lys His Leu same time Gly Glu Ile Leu Ala Ser Phe Tyr 65 70 75 80 Ala Glu wall Phe Lys Ile Ser Arg same time Phe gin Glu same time Ala Leu Lys 85 90 95

Glu Leu Lys Lys 100 (2) 138:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 174 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULA TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) NAME / KEY: various characters (B) LOCATION 1 ... 174 (xi) SEQUENCE DESCRIPTION: Sequence no. 138:

wall Lys Met Arg Phe Phe Ser Gly Phe Gly Phe wall same time Glu Ser wall 1 5 10 15 Leu Phe Glu Glu Trp Leu Leu Lys Gly Ala Tyr Asp wall Ser Gly Phe 20 25 30 Ser Met Gly Ala Ile Lys Ala Ile Glu Tyr Ala Tyr same time Glu wall Leu 35 40 45 gin gin Arg Arg Ile His Ser Leu Leu Leu Phe Ser for Cys Met Leu

275

55 60

Ala His Lys Ser Leu Ala Phe Lys Arg Leu gin Leu Phe Leu Phe gin 65 70 75 80 Lys Asp for gin Ser Tyr Met Asp same time Phe Tyr Lys Glu wall Gly Leu 85 90 95 Asp Ala gin Leu Glu Arg Phe Lys Lys Glu Gly Ser Leu Glu Glu Leu 100 105 110 Glu Phe Leu Leu Asp Tyr Lys Tyr Ser Asp Ser Ile Ile Arg Phe Leu 115 120 125 Leu Glu Lys Gly wall Lys Ile Glu wall Phe Ile Gly Leu Lys Asp Arg 130 135 140 Ile Thr Asp Ile gin Ala Leu Leu Glu Phe Phe Met for Leu wall gin 145 150 155 160 wall Trp gin Phe Lys Asp Cys same time His Leu Leu gin Lys Ser 165 170 (2) INFORMATION FOR SEQUENCE NO. 139:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 471 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear

(Ii) MOLECULA TYPE: protein (Iii) HYPOTHETICAL: YES (Vi) ORIGINAL SOURCE: (A) ORGANISM: Helicobacter pylori (Ix) SIGN: (A) TITLE / KEY: various letters (B) LOCATION 1 ... 471 (Xi) SEQUENCE DESCRIPTION: Sequence no. L39: Met Lys Asn Thr Lys Glu Ile Lys same time Thr Arg Met Lys Lys 1 5 10 15 Gly Tyr Ser Gin Tyr His Thr Leu Lys Lys Gly Leu Leu Lys Thr Ala 20 25 30 Leu Leu Phe Ser Leu For Leu Ser wall Ala Leu Ala Glu Asp Asp Gly 35 40 45 Phe Tyr Met Gly Tyr Gin Ile Gly Gly Ala gin gin same time Ile 50 55 60

276

same time same time Lys Gly Ser Thr Leu Arg same time same time wall Ile Asp Asp Phe Arg 65 70 75 80 gin wall Gly wall Gly Met Ala Gly Gly same time Gly Leu Leu Ala Leu Ala 85 90 95 Thr same time Thr Thr Met Asp Ala Leu Leu Gly Ile Gly same time gin Ile wall 100 105 110 same time Thr same time Thr Thr wall Gly same time same time same time Ala Glu Leu Thr gin Phe 115 120 125 Lys Lys Ile Leu for gin Ile Glu gin Arg Phe Glu Thr same time Lys same time 130 135 140 Ala Tyr Ser wall gin Ala Leu gin wall Tyr Leu Ser same time wall Leu Tyr 145 150 155 160 same time Leu wall same time same time Ser same time same time Gly Ser same time same time Gly wall wall for 165 170 175 Glu Tyr wall Gly Ile Ile Lys wall Leu Tyr Gly Ser gin same time Glu Phe 180 185 190 Ser Leu Leu Ala Thr Glu Ser wall Ala Leu Leu same time Ala Leu Thr Arg 195 200 205 wall same time Leu Asp Ser same time Ser wall Phe Leu Lys Gly Leu Leu Ala gin 210 215 220 Met gin Leu Phe same time Asp Thr Ser Ser Ala Lys Leu Gly gin Ile Ala 225 230 235 240 Glu same time Leu Lys same time Gly Gly Ala Gly Ala Met Leu gin Lys Asp wall 245 250 255 Lys Thr Ile Ser Asp Arg Ile Ala Thr Tyr gin Glu same time Leu Lys gin 260 265 270 Leu Gly Gly Met Leu Lys same time Tyr Asp Glu for Tyr Leu for gin Phe 275 280 285 Gly for Gly Thr Ser Ser gin His Gly wall Ile same time Gly Phe Gly Ile 290 295 300 gin wall Gly Tyr Lys gin Phe Phe Gly Ser Lys Lys same time Ile Gly Leu 305 310 315 320 Arg Tyr Tyr Ala Phe Phe Asp Tyr Gly Phe Thr gin Leu Gly Ser Leu 325 330 335 same time Ser Ala wall Lys Ala same time Ile Phe Thr Tyr Gly Ala Gly Thr Asp 340 345 350 Phe Leu Trp same time Ile Phe Arg Arg wall Phe Ser Asp gin Ser Leu same time 355 360 365 wall Gly wall Phe Gly Gly Ile gin Ile Ala Gly same time Thr Trp Asp Ser 370 375 380 Ser Leu Arg Gly gin Ile Glu same time Ser Phe Lys Glu Tyr for Thr for 385 390 395 400 Thr same time Phe gin Phe Leu Phe same time Leu Gly Leu Arg Ala His Phe Ala

405

410

415

277

Ser Thr Met His Arg 420 Arg Phe Leu Gly Met Glu Phe Gly wall Lys Ile 435 440 Lys Ala same time Gly Ala Asp wall Asp 450 455 Ile same time Tyr Thr Ile Gly Phe 465 470

Ser Ala Ser gin Ser Ile gin His 425 430 for Ala Ile same time gin Arg Tyr Leu 445 Tyr Arg Arg Leu Tyr Ala Phe Tyr 460

(2) INFORMATION FOR SEQUENCE NO.

140:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 129 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULA TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix) SIGN (A) NAME / KEY: Differently letters (B) PLACEMENT 1. . . 129

(xi) SEQUENCE DESCRIPTION: SEQ ID NO. 140:

Met Lys Ser Ile Arg Arg Gly Asp Gly Leu same time wall wall for Phe Ile 1 5 10 15 Asp Ile Met Leu wall Leu Leu Ala Ile wall Leu Ser Ile Ser Thr Phe 20 25 30 Ile Ala gin Gly Lys Ile Lys wall Ser Leu for same time Ala Lys same time Ala 35 40 45 Glu Lys Ser gin for same time Asp gin Lys wall wall wall Ile Ser wall Asp 50 55 60 Glu His Asp same time Ile Phe wall Asp Asp Lys for Thr same time Leu Glu Ala 65 70 75 80 Leu Ser Ala wall wall Lys gin Thr Asp for Lys Thr Leu Ile Asp Leu 85 90 95 Lys Ser Asp Lys Ser Ser Arg Phe Glu Thr Phe Ile Ser Ile Met Asp 100 105 110 Ile Leu Lys Glu His same time His Glu same time Phe Ser Ile Ser Thr gin Ala

278

115 120 125

Gin (2) INFORMATION FOR SEQUENCE NO. 141:

(1) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 75 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULA TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) NAME / KEY: various characters (B) LOCATION 1 ... 75 (xi) SEQUENCE DESCRIPTION: Sequence no. 141:

Met Leu wall Leu Leu Ala Ile wall Leu Ser Ile Ser Thr Phe Ile Ala 1 5 10 15 gin Gly Lys Ile Lys wall Ser Leu for same time Ala Lys same time Ala Glu Lys 20 25 30 Ser Arg for same time Asp gin Lys wall wall wall Ile Ser wall Asp Glu His 35 40 45 Asp same time Ile Phe wall Asp Asp Lys for Thr same time Leu Glu Ala Leu Ser 50 55 60 Ala wall wall Lys gin Thr Asp for Lys Thr Leu 65 70 75

(2) INFORMATION FOR SEQUENCE NO. 142:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 223 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULA TYPE: protein

279

(Iii) HYPOTHETICAL: YES (Vi) ORIGINAL SOURCE: (A) ORGANISM: Helicobacter pylori (Ix) SIGN: (A) TITLE / KEY: (B) LOCATION different characters 1 ... 223 (Xi) SEQUENCE DESCRIPTION: Sequence # 142:

Met Phe Ser Leu Ser Tyr wall Ser Lys Lys Phe Leu Ser wall Leu Leu 1 5 10 15 Leu Ile Ser Leu Phe Leu Ser Ala Cys Lys Ser same time same time Lys Asp Lys 20 25 30 Leu Asp Glu same time Leu Leu Ser Ser Gly Thr gin Ser Ser Lys Glu Leu 35 40 45 same time Asp Lys Arg Asp same time Ile Asp Lys Lys Ser Tyr Ala Gly Leu Glu 50 55 60 Asp wall Phe Leu Asp same time Lys Ser Ile Ser for same time Asp Lys Tyr Met 65 70 75 80 Leu Leu wall Phe Gly Arg same time Gly Cys Ser Tyr Cys Glu Arg Leu Lys 85 90 95 Lys Asp Leu Lys same time wall Lys Glu Leu Arg same time Tyr Ile Lys Glu His 100 105 110 Phe Ser Ala Tyr Tyr wall same time Ile Ser Tyr Ser Lys Glu His same time Phe 115 120 125 Lys wall Gly Asp Lys Asp Lys same time Asp Glu Lys Glu Ile Lys Met Ser 130 135 140 Thr Glu Glu Leu Ala gin Ile Tyr Ala wall gin Ser Thr for Thr Ile 145 150 155 160 wall Leu Ser Asp Lys Thr Gly Lys Thr Ile Tyr Glu Leu for Gly Tyr 165 170 175 Met for Ser wall gin Phe Leu Ala wall Leu Glu Phe Ile Gly Asp Gly 180 185 190 Lys Tyr gin Asp Thr Lys same time Asp Glu Asp Leu Thr Lys Lys Leu Lys 195 200 205 Ala Tyr Ile Lys Tyr Lys Thr same time Leu Ser Lys Ser Lys Ser Ser 210 215 220

(2) INFORMATION FOR SEQUENCE NO. 143:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 116 amino acids

280 (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULA TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) NAME / KEY: various characters (B) LOCATION 1 ... 116 (xi) SEQUENCE DESCRIPTION: Sequence £. 143:

Leu Met Lys 1 Lys 5 Thr His Phe Ile 10 wall Ser Phe Val Leu 15 Ser wall Leu Ser Ala Cys Lys Asp Glu for Lys Lys Ser Ser gin Ser 20 25 30 His gin same time same time Thr Lys Thr Thr gin same time same time gin Ile same time gin for 35 40 45 same time Lys Asp Ile Lys Lys Ile Glu His Glu Glu Glu Asp Glu Lys wall 50 55 60 Thr Lys Glu wall same time Asp Leu Ile same time same time Glu same time Lys Ile Asp Glu 65 70 75 80 Ile same time same time Glu Glu same time Ala Asp for Ser gin Lys Arg Thr same time same time 85 90 95 wall Leu gin Arg Ala Thr same time His gin Asp same time Leu Ser Ser for Leu

100 105 110

Asn Arg Lys Tyr

115 (2) INFORMATION FOR SEQUENCE NO. 144:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 79 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULA TYPE: protein (iii) HYPOTHETICAL: YES

281 (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (Ix) SIGN: (A) TITLE / KEY: different characters (B) LOCATION 1 ... 79 (Xi) SEQUENCE DESCRIPTION: Seq. 144:

Met Phe Glu Lys Ile Arg Lys Ile Leu Ala Asp Ile Glu Asp Ser gin 1 5 10 15 same time Glu Ile Glu Met Leu Leu Lys Leu Ala same time Leu Ser Leu Gly Asp 20 25 30 Phe Ile Glu Ile Lys Arg Gly Ser Met Asp Met for Lys Gly wall same time 35 40 45 Glu Ala Phe Phe Thr gin Leu Ser Glu Glu wall Glu Arg Leu Lys Glu 50 55 60 Leu Ile same time Ala Leu same time Lys Ile Lys Lys Gly Leu Leu wall Phe 65 70 75

(2) INFORMATION FOR SEQUENCE NO. 145:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 51 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULA TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix) SIGN: (A) NAME / KEY: Differently letters (B) PLACEMENT 1 ... 51

(xi) SEQUENCE DESCRIPTION: SEQ ID NO. 145:

Met Ser Met Phe White Ser Asn Leu Ala Phe Thr Ser Glu His Lys Asp 15 10 15

Ala Met Glu Val Ala Lys White Ala White Leu Leu Gly Ser Leu White Ser

25 30

282

Gly White Gly Ala Leu Tyr Leu Phe Ala Leu Asp Lys Arg Ala Ala 35 40 45

Leu Lys Lys 50 (2) SEQ ID NO: 2 146:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 449 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULA TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix) SIGN (A) NAME / KEY: different characters (B) PLACEMENT 1 ... 448

(xi) SEQUENCE DESCRIPTION: SEQ ID NO. 146:

Met Gly Leu Lys Ile Lys Ile Leu Arg Leu Ser Met same time Leu Lys Lys 1 5 10 15 Thr Glu same time Ala Leu Ser Leu Thr Leu Lys same time Phe Ile Lys Ser Glu 20 25 30 Ser Phe Gly Gly Ile Phe Leu Phe Leu same time Ala wall Leu Ala Met wall 35 40 45 wall Ala same time Ser Phe Leu Lys Glu Ser Tyr Phe Ala Leu Trp His Thr 50 55 60 for Phe Gly Phe gin wall Gly Asp Phe Phe Ile Gly Phe Ser Leu His 65 70 75 80 same time Trp Ile Asp Asp wall Leu Met Ala Leu Phe Phe Leu Met Ile Gly 85 90 95 Leu Glu Ile Lys Arg Glu Leu Leu Phe Gly Glu Leu Ser Ser Phe Lys 100 105 110 Lys Ala Ser Phe for wall Ile Ala Ala Ile Gly Gly Met Ile Ala for 115 120 125 Gly Leu Ile Tyr Phe Phe Leu same time Ala same time Thr for Ser gin His Gly 130 135 140 Phe Gly Ile for Met Ala Thr Asp Ile Ala Phe Ala Leu Gly wall Ile

283

145 Met Leu Leu Thr Leu Ala Phe Tyr Thr wall wall 195 Leu Ile 210 for Tyr 225 Ser Gly Ile for wall Lys Gly Lys Arg gin gin 275 Glu Ser 290 for Leu 305 Phe Ile Met Ser Ser Ile Gly Leu Cys Ser Glu 355 Lys His 370 Ile Leu 385 Met Phe Ile Glu wall Ala Ile Gly Ala

435

Gly Lys 150 Arg wall 165 Ala Asp 180 Thr same time Leu wall Leu Ala Leu Leu Leu His Ala 230 Thr Ile 245 for Lys 260 Tyr Ala Glu Ile Leu His Glu Arg Leu for Leu 310 Phe same time 325 Leu Glu 340 Leu Gly Lys Leu Lys Ile Gly Ala Gly Ser same time 390 Leu Lys 405 Ile Ala 420 Leu Tyr Leu

wall for Thr Ala 170 Asp Leu Gly 185 Ala Lys Phe 200 Ala Trp Ile 215 Leu same time Arg Gly wall Leu Leu Ile Ala Ala wall 250 Asp Ser Lys 265 same time Thr Ser 280 Ser Gly Ser 295 Ile Glu Glu Glu His Phe Leu Ala Phe Ala same time 330 wall Asp Lys 345 wall for Leu 360 Gly Ile Thr 375 Ala Arg for Leu Leu Ala Gly Ala Phe Thr Ser 410 Ile Leu Leu 425 Gly Phe Ala 440 Leu Asp

155 Leu Lys wall Ile wall wall Leu Leu Gly 205 Leu same time 220 Ile Trp 235 Phe Cys wall Leu Ala wall Glu Leu wall Leu Leu 285 Lys Ala 300 Ser Ala 315 for Ile Ala Gly wall Leu Leu Gly Phe Leu Ile 365 Lys Gly 380 Ile Ile 395 Gly Phe Glu His Lys Ser Leu Ile Lys Arg Ala 445

Phe Leu 160 Ile Ile 175 Ala Leu 190 Ala Leu Gly Arg Ser Leu wall His gin Phe Met 240 Ile Leu 255 Glu Leu 270 Thr Lys Glu Ala Leu gin Ser Gly Tyr Ser wall 320 Asp wall 335 Ile Leu 350 Thr Phe Ile Gly Trp Trp Thr Met Ser Asp Ala 400 Met Ser 415 Gly Ile 430 Ala Leu Lys

Lys (1)

FOR

No. 147:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 815 amino acids

284 (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULA TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix) SIGN: (A) NAME / KEY: different characters (B) PLACEMENT 1 ... 816

(xi) SEQUENCE DESCRIPTION: SEQ ID NO. 147:

Met same time Asp Lys Arg Phe Arg Lys Tyr Cys Ser Phe Ser Ile Phe Leu 1 5 10 15 Ser Leu Leu Gly Thr Phe Glu Leu Glu Ala Lys Glu Glu Glu Lys Glu 20 25 30 Glu Lys Lys Thr Glu Arg same time Lys Asp Lys Glu Lys same time Ala gin His 35 40 45 Thr Leu Gly Lys wall Thr Thr gin Ala Ala Lys Ile Phe same time Tyr same time 50 55 60 same time gin Thr Thr Ile Ser Ser Lys Glu Leu Glu Arg Arg gin Ala same time 65 70 75 80 gin Ile Ser Asp Met Phe Arg Arg same time for same time Ile same time wall Gly Gly 85 90 95 Gly Ala wall Ile Ala gin Lys Ile Tyr wall Arg Gly Ile Glu Asp Arg 100 105 110 Leu Ala Arg wall Thr wall Asp Gly wall Ala gin Met Gly Ala Ser Tyr 115 120 125 Gly His gin Gly same time Thr Ile Ile Asp for Gly Met Leu Lys Ser wall 130 135 140 wall wall Thr Lys Gly Ala Ala gin Ala Ser Ala Gly for Met Ala Leu 145 150 155 160 Ile Gly Ala Ile Lys Met Glu Thr Arg Ser Ala Ser Asp Phe Ile for 165 170 175 Lys Gly Lys Asp Tyr Ala Ile Ser Gly Ala Ala Thr Phe Leu Thr same time 180 185 190 Phe Gly Asp Arg Glu Thr Ile Met Gly Ala Tyr Arg same time His His Phe 195 200 205 Asp Ala Leu Leu Tyr Tyr Thr His gin same time Ile Phe Tyr Tyr Arg Asp

210 215 220

285

Gly Asp same time Ala Met Lys same time Leu Phe Asp for Lys Ala Asp same time Lys 225 230 235 240 wall Thr Ala Ser for Ser Glu gin same time same time wall Met Ala Lys Ile same time 245 250 255 Gly Tyr Leu Ser Glu Arg Asp Thr Leu Thr Leu Ser Tyr same time Met Thr 260 265 270 Arg Asp same time Ala same time Arg for Leu Arg Ala same time Phe Thr Gly Thr Phe 275 280 285 Leu for Tyr Ser Cys Gly Asp Phe same time Ala Phe for same time Glu Lys same time 290 295 300 for Ser Asp Cys Leu Phe Glu same time Asp Ala Ser Leu Phe Lys Thr Tyr 305 310 315 320 Ser wall same time Leu wall His same time wall Ser Leu same time Tyr Glu Arg Glu Gly 325 330 335 Gly Ser Arg Phe Gly Asp for Lys Leu Lys Ile same time Gly Tyr Thr Ser 340 345 350 Ile Arg same time wall gin Ile Asp for Leu Phe Arg for Ser Asp Ile Ala 355 360 365 Thr Thr Ile for Phe Thr for same time for gin Leu Ser gin Gly Glu Glu 370 375 380 same time gin Cys wall Ala gin Gly Gly Ile Tyr Asp Ala Leu Lys gin Thr 385 390 395 400 Cys Ser Ile Thr Phe Lys Ser Leu Gly Gly Gly Ser wall wall Ala same time 405 410 415 Lys same time Leu Phe Ile Ile same time Ser Gly Phe same time Ala same time wall Ile His 420 425 430 Thr Ile Asp His Lys same time Asp same time Leu Leu Glu Tyr Gly Leu same time Tyr 435 440 445 gin same time Leu Thr Thr Phe Asp Lys Ala Ile for Asp Ser Glu Leu wall 450 455 460 Lys for Gly Asp Ala for Asp Ala Cys Leu Arg wall Thr Gly for Asp 465 470 475 480 Asp for same time Met same time Gly Arg Cys gin Arg same time Gly Ala Thr Ala same time 485 490 495 wall wall Gly wall Tyr Ala gin Ala same time Tyr Thr Leu His for Met wall 500 505 510 Thr Leu Gly Ala Gly Thr Arg Tyr Asp wall Tyr Thr Leu wall Asp Lys 515 520 525 Asp Trp gin Leu His wall Thr gin Gly Phe Ser for Ser Ala Ala Leu 530 535 540 same time wall Ser for Leu Glu same time Leu same time Phe Arg Leu Ser Tyr Ala Tyr 545 550 555 560 wall Thr Arg Gly for Met for Gly Gly Leu wall Trp Met Arg gin Asp

565

570

575

286

Asn Leu Arg Tyr 580 Asn Arg Asn Leu Lys 585 For Glu White Gly gin 590 Asn Ala Glu Phe same time Thr Glu Tyr Ser Ser gin Tyr Phe Asp Phe Arg Ala Ala 595 600 605 Gly Phe wall gin Leu Ile Ser same time Tyr Ile same time gin Phe Ser Ser Thr 610 615 620 Leu Phe wall Thr same time Leu for Ala gin Asp Ile Ile Tyr wall for Gly 625 630 635 640 Tyr Glu wall Ser Gly Thr Ala Lys Tyr Lys Gly Phe Ser Leu Gly Leu 645 650 655 Ser wall Ala Arg Ser Trp for Ser Leu Lys Gly Arg Leu Ile Ala Asp 660 665 670 wall Tyr Glu Leu Ala Ala Thr Thr Gly same time wall Phe Ile Leu Thr Ala 675 680 685 Ser Tyr Thr Ile for Arg Thr Gly Leu Ser Ile Thr Trp Leu Ser Arg 690 695 700 Phe wall Thr same time Leu Ser Tyr Cys Ser Tyr Ser for Tyr Arg same time Gly 705 710 715 720 for Thr Asp Ile Asp Arg Arg for Ser same time Cys for Lys Thr for Gly 725 730 735 Ile Phe His wall His Lys for Gly Tyr Gly wall Ser Ser Phe Phe Ile 740 745 750 Thr Tyr Lys for Thr Tyr Lys Lys Leu Lys Gly Leu Ser Leu same time Ala 755 760 765 wall Phe same time same time wall Phe same time gin gin Tyr Ile Asp gin Ala Ser for 770 775 780 wall Met Ser for Asp Glu for same time gin Asp Lys Tyr Ala Arg Gly Met 785 790 795 800 Ala Glu for Gly Phe same time Ala Arg Phe Glu Ile Ser Tyr Lys Phe 805 810 815

(2) INFORMATION FOR SEQUENCE NO. 148:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 814 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULA TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori

287 (ix) SIGN:

(A) NAME / KEY: various characters (B) LOCATION 1 ... 814 (xi) SEQUENCE DESCRIPTION: Sequence no. 148:

Met Thr Ser wall Leu Glu Lys Tyr Cys Ser Phe Ser Ile Phe Leu Ser 1 5 10 15 Leu Leu Gly Thr Phe Glu Leu Glu Ala Lys Glu Glu Glu Lys Glu Glu 20 25 30 Lys Lys Thr Glu Arg same time Lys Asp Lys Glu Lys same time Ala gin His Thr 35 40 45 Leu Gly Lys wall Thr Thr gin Ala Ala Lys Ile Phe same time Tyr same time same time 50 55 60 gin Thr Thr Ile Ser Ser Lys Glu Leu Glu Arg Arg gin Ala same time gin 65 70 75 80 Ile Ser Asp Met Phe Arg Arg same time for same time Ile same time wall Gly Gly Gly 85 90 95 Ala wall Ile Ala gin Lys Ile Tyr wall Arg Gly Ile Glu Asp Arg Leu 100 105 110 Ala Arg wall Thr wall Asp Gly wall Ala gin Met Gly Ala Ser Tyr Gly 115 120 125 His gin Gly same time Thr Ile Ile Asp for Gly Met Leu Lys Ser wall wall 130 135 140 wall Thr Lys Gly Ala Ala gin Ala Ser Ala Gly for Met Ala Leu Ile 145 150 155 160 Gly Ala Ile Lys Met Glu Thr Arg Ser Ala Ser Asp Phe Ile for Lys 165 170 175 Gly Lys Asp Tyr Ala Ile Ser Gly Ala Ala Thr Phe Leu Thr same time Phe 180 185 190 Gly Asp Arg Glu Thr Ile Met Gly Ala Tyr Arg same time His His Phe Asp 195 200 205 Ala Leu Leu Tyr Tyr Thr His gin same time Ile Phe Tyr Tyr Arg Asp Gly 210 215 220 Asp same time Ala Met Lys same time Leu Phe Asp for Lys Ala Asp same time Lys wall 225 230 235 240 Thr Ala Ser for Ser Glu gin same time same time wall Met Ala Lys Ile same time Gly 245 250 255 Tyr Leu Ser Glu Arg Asp Thr Leu Thr Leu Ser Tyr same time Met Thr Arg 260 265 270 Asp same time Ala same time Arg for Leu Arg Ala same time Phe Thr Gly Thr Phe Leu 275 280 285 for Tyr Ser Cys Gly Asp Phe same time Ala Phe for same time Glu Lys same time for

288

290

295

300

Ser Asp Cys Leu Phe Glu same time Asp Ala Ser Leu Phe Lys Thr Tyr Ser 305 310 315 320 wall same time Leu wall His same time wall Ser Leu same time Tyr Glu Arg Glu Gly Gly 325 330 335 Ser Arg Phe Gly Asp for Lys Leu Lys Ile same time Gly Tyr Thr Ser Ile 340 345 350 Arg same time wall gin Ile Asp for Leu Phe Arg for Ser Asp Ile Ala Thr 355 360 365 Thr Ile for Phe Thr for same time for gin Leu Ser gin Gly Glu Glu same time 370 375 380 gin Cys wall Ala gin Gly Gly Ile Tyr Asp Ala Leu Lys gin Thr Cys 385 390 395 400 Ser Ile Thr Phe Lys Ser Leu Gly Gly Gly Ser wall wall Ala same time Lys 405 410 415 same time Leu Phe Ile Ile same time Ser Gly Phe same time Ala same time wall Ile His Thr 420 425 430 Ile Asp His Lys same time Asp same time Leu Leu Glu Tyr Gly Leu same time Tyr gin 435 440 445 same time Leu Thr Thr Phe Asp Lys Ala Ile for Asp Ser Glu Leu wall Lys 450 455 4 60 for Gly Asp Ala for Asp Ala Cys Leu Arg wall Thr Gly for Asp Asp 465 470 475 480 for same time Met same time Gly Arg Cys gin Arg same time Gly Ala Thr Ala same time wall 485 490 495 wall Gly wall Tyr Ala gin Ala same time Tyr Thr Leu His for Met wall Thr 500 505 510 Leu Gly Ala Gly Thr Arg Tyr Asp wall Tyr Thr Leu wall Asp Lys Asp 515 520 525 Trp gin Leu His wall Thr gin Gly Phe Ser for Ser Ala Ala Leu same time 530 535 540 T wall Ser for Leu Glu same time Leu same time Phe Arg Leu Ser Tyr Ala Tyr wall 545 550 555 560 Thr Arg Gly for Met for Gly Gly Leu wall Trp Met Arg gin Asp same time 565 570 575 Leu Arg Tyr same time Arg same time Leu Lys for Glu Ile Gly gin same time Ala Glu 580 585 590 Phe same time Thr Glu Tyr Ser Ser gin Tyr Phe Asp Phe Arg Ala Ala Gly 595 600 605 Phe wall gin Leu Ile Ser same time Tyr Ile same time gin Phe Ser Ser Thr Leu 610 615 620 Phe wall Thr same time Leu for Ala gin Asp Ile Ile Tyr wall for Gly Tyr 625 630 635 640 Glu wall Ser Gly Thr Ala Lys Tyr Lys Gly Phe Ser Leu Gly Leu Ser

289

645 650 655 wall Ala Arg Ser Trp for Ser Leu Lys Gly Arg Leu Ile Ala Asp wall 660 665 670 Tyr Glu Leu Ala Ala Thr Thr Gly same time wall Phe Ile Leu Thr Ala Ser 675 680 685 Tyr Thr Ile for Arg Thr Gly Leu Ser Ile Thr Trp Leu Ser Arg Phe 690 695 700 wall Thr same time Leu Ser Tyr Cys Ser Tyr Ser for Tyr Arg same time Gly for 705 710 715 720 Thr Asp Ile Asp Arg Arg for Ser same time Cys for Lys Thr for Gly Ile 725 730 735 Phe His wall His Lys for Gly Tyr Gly wall Ser Ser Phe Phe Ile Thr 740 745 750 Tyr Lys for Thr Tyr Lys Lys Leu Lys Gly Leu Ser Leu same time Ala wall 755 760 765 Phe same time same time wall Phe same time gin gin Tyr Ile Asp gin Ala Ser for wall 770 775 780 Met Ser for Asp Glu for same time gin Asp Lys Tyr Ala Arg Gly Met Ala 785 790 795 800 Glu for Gly Phe same time Ala Arg Phe Glu Ile Ser Tyr Lys Phe 805 810

(2) INFORMATION FOR SEQUENCE NO. 149:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 527 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii, MOLECULA TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) NAME / KEY: various characters (B) LOCATION 1 ... 527 (xi) SEQUENCE DESCRIPTION: Sequence no. 149:

Met Lys Gin Asn Leu Lys Pro Phe Lys Met Lys Glu Asn Leu Met 15 10 15

290

Thr

Ser

Thr

Gly

Thr

Gly

Leu

same time

Cys

145

Lys

same time

Ala

gin

Gly

225

Thr

Ala

Leu

Ser

Thr

305

Thr

Leu

Gly

gin Ser gin Lys wall Arg Phe Leu Ala for Leu Ser Leu Ala Leu 20 25 30 Leu Ser Phe same time for wall Gly Ala Glu Glu Asp Gly Gly Phe Met 35 40 45 Phe Gly Tyr Glu Leu Gly gin wall wall gin gin wall Lys same time for 50 55 60 Lys Ile Lys Ala Glu Glu Leu Ala Gly Leu Leu same time Ser Thr Thr 70 75 80 same time same time Thr same time Ile same time Ile Ala Gly Thr Gly Gly same time wall Ala 85 90 95 Thr Leu Gly same time Leu Phe Met same time gin Leu Gly same time Leu Ile Asp 100 105 110 Tyr for Thr Leu Lys Thr same time same time Leu His gin Cys Gly Ser Thr 115 120 125 Ser Gly same time Gly Ala Thr Ala Ala Ala Ala Thr same time same time Ser for 130 135 140 Phe gin Gly same time Leu Ala Leu Tyr same time Glu Met wall Asp Ser Ile 150 155 160 Thr Leu Ser gin same time Ile Ser Lys same time Ile Phe gin Gly Asp same time 165 170 175 Thr Thr Ser Ala same time Leu Ser same time gin Leu Ser Glu Leu same time Thr 180 185 190 Ser wall Tyr Leu Thr Tyr Met same time Ser Phe Leu same time Ala same time same time 195 200 205 Ala Gly Gly Ile Phe gin same time same time Thr same time gin Ala Tyr Glu same time 210 215 220 wall Thr Ala gin gin Ile Ala Tyr wall Leu Lys gin Ala Ser Ile 230 235 240 Met Gly for Ser Gly Asp Ser Gly Ala Ala Gly Ala Phe Leu Asp 245 250 255 Ala Leu Ala gin His wall Phe same time Ser Ala same time Ala Gly same time Asp 260 265 270 Ser Ala Lys Glu Phe Thr Ser Leu wall gin same time Ile wall same time same time 275 280 285 gin same time Ala Leu Thr Leu Ala same time same time Ala same time Ile Ser same time Ser 290 295 300 Gly Tyr gin wall Ser Tyr Gly Gly same time Ile Asp gin Ala Arg Ser 310 315 320 gin Leu Leu same time same time Thr Thr same time Thr Leu Ala Lys wall Thr Ala 325 330 335 same time same time Glu Leu Lys Ala same time for Trp Leu Gly same time Phe Ala Ala 340 345 350 same time Ser Ser gin wall same time Ala Phe same time Gly Phe Ile Thr Lys Ile 355 360 365

291

Gly Tyr Lys 370 Phe Gly Glu Asn Val Gly Leu Arg Tyr 375 380 Tyr Gly Phe Phe Ser Tyr Asn Gly Ala Gly Val Gly Asn Gly For Thr 385 390 395 400 Gin Val Asn Leu Leu Thr Tyr Gly Val Gly Thr Asp 405 410 415 Asr Val Phe Ser Arg Ser Phe Gly Ser Arg Ser Leu Asn Ala Gly 420 425 430 Phe Phe Gly Gly White gin Leu Ala Gly Asp Thr Tyr White Ser Thr Leu 435 440 445 Arg Asn Ser Pro Gin Leu Ala Ser Arg Pro Lys Phe Gin 450 455 4 60 Phe Leu Phe Gly Leu Arg Met Asn Phe Gly White Leu Lys Lys 465 470 475 480 Asp Leu Lys Ser His same time Gin His Ser ile Glu White Gly Val Gin White 485 4 90 495 For Thrile Tyr Asn Thr Lys Ala Gly Gly Glu Glu Val Lys 500 505 510 Tyr Phe Arg For Tyr Ser Val Tyr Trp Val Tyr Gly Tyr Ala Phe 515 520 525 (2) INFORMATION FOR SEQUENCE NO. 150:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 459 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULA TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) NAME / KEY: miscellaneous characters (B) LOCATION 1 ... 459 (xi) SEQUENCE DESCRIPTION: Sequence no. 150:

wall wall Leu Leu Thr Met Thr Lys Arg Leu Phe Lys Gly Leu Leu Ala 1 5 10 15 Ile Ser Leu Ala wall Ser Leu His Gly Gly Glu wall Lys Glu Lys Lys

292

for wall Lys for wall Lys Glu Asp for gin Glu Leu Ala Ala Lys Arg 35 40 45 wall Glu Ala Phe Ser Arg Phe Ser same time wall wall Thr Glu Ile Glu Lys 50 55 60 Lys Tyr wall Asp Lys Ile Ser Ile Ser Glu Ile Met Thr Lys Ala Ile 65 70 75 80 Glu Gly Leu Leu Ser same time Leu Asp Ala His Ser Ala Tyr Leu same time Glu 85 90 95 Lys Lys Phe Lys Glu Phe gin Ala gin Thr Glu Gly Glu Phe Gly Gly 100 105 110 Leu Gly Ile Thr wall Gly Met Arg Asp Gly wall Leu Thr wall Ile Ala 115 120 125 for Leu Glu Gly Thr for Ala Tyr Lys Ala Gly wall Lys Ser Gly Asp 130 135 140 Ser Ile Leu Lys Ile same time same time Glu Ser Thr Leu Ser Met Ser Ile Asp 145 150 155 160 Asp Ala wall same time Leu Met Arg Gly Lys for Lys Thr Ser Ile gin Ile 165 170 175 Thr wall wall Arg Lys same time Glu for Lys for Leu wall Phe same time Ile wall 180 185 190 Arg Asp Ile Ile Lys Ile for Ser wall Tyr wall Lys Lys Ile Lys Asp 195 200 205 Thr for Tyr Leu Tyr wall Arg wall same time Ser Phe Asp Lys same time wall Thr 210 215 220 Lys Ser wall Leu Asp Gly Leu Lys Ala same time for same time Ile Lys Gly wall 225 230 235 240 wall Leu Asp Leu Arg Gly same time for Gly Gly Leu Leu same time gin Ala wall 245 250 255 Gly Leu Ser same time Leu Phe Ile Lys Glu Gly wall Leu wall Ser gin Arg 260 265 270 Gly Lys same time Lys Glu Glu same time Leu Glu Tyr Lys Ala same time Gly Arg Ala 275 280 285 for Tyr Thr same time Leu for wall wall wall Leu wall same time Gly Gly Ser Ala 290 295 300 Ser Ala Ser Glu Ile wall Ala Gly Ala Leu gin Asp His Lys Arg Ala 305 310 315 320 Ile Ile Ile Gly Glu Lys Thr Phe Gly Lys Gly Ser wall gin wall Leu 325 330 335 Leu for wall same time Lys Asp Glu Ala Ile Lys Ile Thr Thr Ala Arg Tyr 340 345 350 Tyr Leu for Ser Gly Arg Thr Ile gin Ala Lys Gly Ile Thr for Asp 355 360 365 Ile wall Ile Tyr for Gly Lys wall for Glu same time Glu same time Lys Phe Ser

293

370 375 380 Leu Lys Glu Ala Asp Leu Lys HLS His Leu Glu gin Glu Leu Lys Lys 385 390 395 400 Leu Asp Asp Lys Thr for Ile Ser Lys Glu Ala Asp Lys Asp Lys Lys 405 410 415 Ser Glu Glu Glu Lys Glu wall Thr for Lys Met Ile same time Asp Asp Ile 420 425 430 gin Leu Lys Thr Ala Ile Asp Ser Leu Lys Thr Trp Ser Ile wall Asp 435 440 445 Glu Lys Met Asp Glu Lys wall for Lys Lys Lys 450 455

(2) INFORMATION FOR SEQUENCE NO. 151:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 104 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULA TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) NAME / KEY: various characters (B) LOCATION 1 ... 104 (xi) SEQUENCE DESCRIPTION: Sequence no. 151:

Leu 1 Leu Leu His for 5 Leu His Ala His Ala Gin Val Leu Gly Phe Thr 10 15 same time His Asp His Ala for Trp Leu Tyr Asp Phe Ile Lys Ser Phe Cys 20 25 30 same time Leu Ser Gly gin for Phe Leu Asp Leu gin Ala Phe Ala Ile same time 35 40 45 Phe same time Glu Phe Ser Asp Arg Ala same time Ala Tyr same time Leu Phe Leu Arg 50 55 60 Asp Ile Ser His Ala same time Ile for Lys Lys Arg Glu gin Met wall Leu 65 70 75 80 Ala Ser Gly wall Lys Phe same time wall Leu Ser His Tyr His Phe Ile Ala 85 90 95

294

Asn Ala Leu Lys Clay Arg Ala Phe 100 (2) 152:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 165 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULA TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix) SIGN: (A) TITLE / KEY: different characters (B) LOCATION 1 ... 165

(xi) SEQUENCE DESCRIPTION: SEQ ID NO. 152:

Met Ile Glu Leu Ile Leu His same time Lys Ser Ile gin Ile Asp Glu Thr 1 5 10 15 Leu Leu same time wall Lys Glu His Leu Glu Lys Phe Tyr Ser same time Lys Glu 20 25 30 gin Glu Thr Ile Ala Lys Thr Leu Glu Ser gin Thr Glu Leu Thr Cys 35 40 45 Ser Tyr Leu Leu Asp Lys Asp Phe Ser Leu Leu Glu Lys His Leu Glu 50 55 60 same time Ser Leu Gly His Phe Thr Phe Glu Ser Glu Phe Ala Leu Leu Lys 65 70 75 80 Asp Lys Glu for Leu same time Leu Ala gin Ile Lys gin Ile Gly wall Leu 85 90 95 Lys wall Ile Thr Tyr Glu Met Thr gin Ala Leu Lys same time gin Ile Ile 100 105 110 His Leu Thr gin Ile wall same time Glu Glu same time Leu Glu Phe Asp Glu Glu 115 120 125 Leu wall Ile Tyr His Leu same time Phe Lys Leu same time gin same time Thr Tyr Lys 130 135 140 wall Leu Ala Lys Phe Cys wall Leu Lys Lys Lys Gly Thr Leu His Glu 145 150 155 160 Lys Phe Lys Ala Phe

295

165 (2) INFORMATION FOR SEQUENCE NO. 153:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 213 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULA TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) TITLE / KEY: various characters (B) LOCATION 1 ... 213 (xi) SEQUENCE DESCRIPTION: Sequence no. 153:

Met 1 Asp Thr Glu Thr 5 gin Glu Lys Phe Leu Phu Glu Lys 10 15 Ala Leu gin Lys same time Leu gin Ala Tyr Trp Ile Thr Thr Thr Glu Thr 20 25 30 Lys same time Glu Leu Thr Arg Glu Glu Phe Ser same time Leu Ile Arg Lys Thr 35 40 45 Met Ile Glu Leu Ile Leu His same time Lys Ser Ile gin Ile Asp Glu Thr 50 55 60 Leu Leu same time wall Lys Glu His Leu Glu Lys Phe Tyr Ser same time Lys Glu 65 70 75 80 gin Glu Thr Ile Ala Lys Thr Leu Glu Ser gin Thr Glu Leu Thr Cys 85 90 95 Ser Tyr Leu Leu Asp Lys Asp Phe Ser Leu Leu Glu Lys His Leu Glu 100 105 110 same time Ser Leu Gly His Phe Thr Phe Glu Ser Glu Phe Ala Leu Leu Lys 115 120 125 Asp Lys Glu for Leu same time Leu Ala gin Ile Lys gin Ile Gly wall Leu 130 135 140 Lys wall Ile Thr Tyr Glu Met Thr gin Ala Leu Lys same time gin Ile Ile 145 150 155 160 His Leu Thr gin Ile wall same time Glu Glu same time Leu Glu Phe Asp Glu Glu

165 170 175

296

Leu Val Tyr His 180 Leu Asn Phe Lys Leu Asn Thr Thr Tyr Lys 185 190 wall Leu Ala Lys Phe Cys wall Leu Lys Lys Lys Gly Thr Leu His Glu 195 200 205 Lys Phe Lys Ala Phe

210 (2) INFORMATION FOR SEQUENCE NO. 154

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 253 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULA TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) NAME / KEY: various characters (B) LOCATION 1 ... 253 (xi) SEQUENCE DESCRIPTION: Sequence no. 154

Met Ala Ile Ser Ile Lys Ser for Lys Glu Ile Lys Ala Leu Arg Lys 1 5 10 15 Ala Gly Glu Leu Thr Ala gin Ala Leu Ala Leu Leu Glu Arg Glu wall 20 25 30 Arg for Gly wall Ser Leu Leu Glu Leu Asp Lys Met Ala Glu Asp Phe 35 40 45 Ile Lys Ser Ser His Ala Arg for Ala Phe Lys Gly Leu Tyr Gly Phe 50 55 60 for same time Ser wall Cys Met Ser Leu same time Glu wall wall Ile His Gly Ile 65 70 75 80 for Thr Asp Tyr wall Leu gin Glu Gly Asp Ile Ile Gly Leu Asp Leu 85 90 95 Gly wall Glu wall Asp Gly Tyr Tyr Gly Asp Ser Ala Leu Thr Leu for 100 105 110 Ile Gly Ala Ile Ser for gin Asp Glu Lys Leu Leu Ala Cys Ser Lys 115 120 125 Glu Ser Leu Met His Ala Ile Ser Ser Ile Arg wall Gly Met His Phe

297

130 135 140 Lys Glu Leu Ser gin Ile Leu Glu Gly Ala Ile Thr Glu Arg Gly Phe 145 150 155 160 wall for Leu Lys Gly Phe Cys Gly His Gly Ile Gly Lys Lys for His 165 170 175 Glu Glu for Glu Ile for same time Tyr Leu Glu Lys Gly wall Lys Ala same time 180 185 190 Ser Gly for Lys Ile Lys Glu Gly Met wall Phe Cys Leu Glu for Met 195 200 205 wall Cys gin Lys gin Gly Glu for Lys Ile Leu Ala Asp Lys Trp Ser 210 215 220 wall wall Ser wall Asp Gly Leu same time Thr Ser His His Glu His Thr Ile 225 230 235 240 Ala Ile wall Gly same time Lys Ala wall Ile Leu Thr Glu Arg 245 250

(2) INFORMATION FOR SEQUENCE NO. 155:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 247 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULA TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix) SIGN: (A) NAME / KEY: different characters (B) PLACEMENT 1 ... 247

(xi) SEQUENCE DESCRIPTION: SEQ ID NO. 155:

Lys for Lys Arg same time gin Ser for Lys Lys Ser Arg Glu Leu Thr Ala 1 5 10 15 gin Ala Leu Ala Leu Leu Glu Arg Glu wall Arg for Gly wall Ser Leu 20 25 30 Leu Glu Leu Asp Lys Met Ala Glu Asp Phe Ile Lys Ser Ser His Ala 35 40 45 Arg for Ala Phe Lys Gly Leu Tyr Gly Phe for same time Ser wall Cys Met 50 55 60

298

Ser Leu same time Glu wall wall Ile His Gly Ile for Thr Asp Tyr wall Leu 65 70 75 80 gin Glu Gly Asp Ile Ile Gly Leu Asp Leu Gly wall Glu wall Asp Gly 85 90 95 Tyr Tyr Gly Asp Ser Ala Leu Thr Leu for Ile Gly Ala Ile Ser for 100 105 110 gin Asp Glu Lys Leu Leu Ala Cys Ser Lys Glu Ser Leu Met His Ala 115 120 125 Ile Ser Ser Ile Arg wall Gly Met His Phe Lys Glu Leu Ser gin Ile 130 135 140 Leu Glu Gly Ala Ile Thr Glu Arg Gly Phe wall for Leu Lys Gly Phe 145 150 155 160 Cys Gly His Gly Ile Gly Lys Lys for His Glu Glu for Glu Ile for 165 170 175 same time Tyr Leu Glu Lys Gly wall Lys Ala same time Ser Gly for Lys Ile Lys 180 185 190 Glu Gly Met wall Phe Cys Leu Glu for Met wall Cys gin Lys gin Gly 195 200 205 Glu for Lys Ile Leu Ala Asp Lys Trp Ser wall wall Ser wall Asp Gly 210 215 220 Leu same time Thr Ser His His Glu His Thr Ile Ala Ile wall Gly same time Lys 225 230 235 240 Ala wall Ile Leu Thr Glu Arg

245 (2) INFORMATION FOR SEQUENCE NO. 156:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 340 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULA TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix) SIGN: (A) NAME / KEY: different characters (B) PLACEMENT 1 ... 340

(xi) SEQUENCE DESCRIPTION: SEQ ID NO. 156:

299

Met Tyr Arg Lys Asp Leu Asp same time Tyr Leu Lys gin Arg Leu for Lys 1 5 10 15 Ala wall Phe Leu Tyr Gly Glu Phe Asp Phe Phe Ile His Tyr Tyr Ile 20 25 30 gin Thr Ile Ser Ala Leu Phe Lys Gly same time same time for Asp Thr Glu Thr 35 40 45 Ser Leu Phe Tyr Ala Ser Asp Tyr Glu Lys Ser gin Ile Ala Thr Leu 50 55 60 Leu Glu gin Asp Ser Leu Phe Gly Gly Ser Ser Leu wall Ile Leu Lys 65 70 75 80 Leu Asp Phe Ala Leu His Lys Lys Phe Lys Glu same time Asp Ile same time for 85 90 95 Phe Leu Lys Ala Leu Glu Arg for Ser His same time Arg Leu Ile Ile Gly 100 105 110 Leu Tyr same time Ala Lys Ser Asp Thr Thr Lys Tyr Lys Tyr Thr Ser Glu 115 120 125 Ile Ile wall Lys Phe Phe gin Lys Ser for Leu Lys Asp Glu Ala Ile 130 135 140 Cys wall Arg Phe Phe Thr for Lys Ala Trp Glu Ser Leu Lys Phe Leu 145 150 155 160 gin Glu Arg Ala same time Phe Leu His Leu Asp Ile Ser Gly His Leu Leu 165 170 175 same time Ala Leu Phe Glu Ile same time same time Glu Asp Leu Ser wall Ser Phe same time 180 185 190 Asp Leu Asp Lys Leu Ala wall Leu same time Ala for Ile Thr Leu Glu Asp 195 200 205 Ile gin Glu Leu Ser Ser same time Ala Gly Asp Met Asp Leu gin Lys Leu 210 215 220 Ile Leu Gly Leu Phe Leu Lys Lys Ser wall Leu Asp Ile Tyr Asp Tyr 225 230 235 240 Leu Leu Lys Glu Gly Lys Lys Asp Ala Asp Ile Leu Arg Gly Leu Glu 245 250 255 Arg Tyr Phe Tyr gin Leu Phe Leu Phe Phe Ala His Ile Lys Thr Thr 260 265 270 Gly Leu Met Asp Ala Lys Glu wall Leu Gly Tyr Ala for for Lys Glu 275 280 285 Ile wall Glu same time Tyr Ala Lys same time Ala Leu Arg Leu Lys Glu Ala Gly 290 295 300 Tyr Lys Arg wall Phe Glu Ile Phe Arg Leu Trp His Leu gin Ser Met 305 310 315 320 gin Gly gin Lys Glu Leu Gly Phe Leu Tyr Leu Thr for Ile gin Lys

325

330

335 white Asn Pro white

300

340 (2) INFORMATION FOR SEQUENCE NO. 157:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 200 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULA TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix) SIGN: (A) NAME / KEY: different characters (B) PLACEMENT 1 ... 200

(xi, SEQUENCE DESCRIPTION: SEQ ID NO 157:

wall Phe Met Thr Ser Ala Leu Leu Gly Leu gin Ile wall Leu Ala wall 1 5 10 15 Leu Ile wall wall wall wall Leu Leu gin Lys Ser Ser Ser Ile Gly Leu 20 25 30 Gly Ala Tyr Ser Gly Ser same time Asp Ser Leu Phe Gly Ala Lys Gly for 35 40 45 Ala Ser Phe Met Ala Lys Leu Thr Met Phe Leu Gly Leu Leu Phe wall 50 55 60 Ile same time Thr Ile Ala Leu Gly Tyr Phe Tyr same time Lys Glu Tyr Gly Lys 65 70 75 80 Ser wall Leu Asp Glu Thr Lys Thr same time Lys Glu Leu Ser for Leu wall 85 90 95 for Ala Thr Gly Thr Leu same time for Thr Leu same time for Thr Leu same time for 100 105 110 Thr Leu same time for Leu Glu gin Ala for Thr same time for Leu Met for Thr 115 120 125 gin Thr for Lys Glu Leu for Lys Glu for Ala Lys Thr for Phe wall 130 135 140 Glu Ser for Lys gin same time Glu Lys same time Glu Lys same time Asp Ala Lys Glu 145 150 155 160 same time Gly Ile Lys Gly wall Glu Lys same time Lys Glu same time Ala Lys Thr for 165 170 175

301

For Thr Thr His 180 Gin Lys For Lys Lys Asp Glu Lys 200 Thr His Ala 185 190 Thr Asn Gin Lys 195 (2) INFORMATION FOR SEQUENCE NO. 158:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 159 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULA TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix) SIGN (A) NAME / KEY: different characters (B) PLACEMENT 1 ... 159

(xi) SEQUENCE DESCRIPTION: Sequence £. 158:

Met Arg Ser Pro Asn Leu Glu Lys Glu Glu Thr Glu White Glu Thr 1 5 10 15 Leu Leu wall Arg Glu Lys Met Arg Leu Cys for Leu Tyr Trp Arg Ile 20 25 30 Leu Ala Phe Leu Ile Asp Ser Leu Leu wall Ala Phe Leu Leu Ser Asp 35 40 45 Leu Leu Arg Ala Cys Ala Phe Leu His Ser Leu Tyr Trp Leu Thr same time 50 55 60 for Ile Tyr Tyr Ser Ala Phe wall wall Met Gly Phe Ile Ile Leu Tyr 65 70 75 80 Gly wall Tyr Glu Ile Phe Phe wall Cys Leu Cys Lys Met Ser Leu Ala 85 90 95 Lys Leu wall Phe Arg Ile Lys Ile Ile Asp Ile Tyr Leu Ala Asp Cys 100 105 110 for Ser Arg Ala Ile Leu Leu Lys Arg Leu Gly Leu Lys Ile wall wall 115 120 125 Phe Leu Cys for Phe Leu Trp Phe wall wall Phe Lys same time for Tyr His 130 135 140 Arg Ala Trp His Glu Glu Lys Ser Lys Ser Leu Leu wall Leu Phe

302

145 150 155 (2) INFORMATION FOR SEQUENCE NO. 159:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 234 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULA TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (Ix) SIGN: (A) NAME / KEY: different characters (B) PLACEMENT 1 ... 234 (Xi) SEQUENCE DESCRIPTION: Sequence # 159:

Leu same time Thr Asp Phe Ser His Ile Thr Asp Ile Glu Gly Met Arg Phe 1 5 10 15 wall same time Glu Glu Asp Ala Leu same time Lys Leu Ile same time Glu Ile His Thr 20 25 30 Arg His Ile Asp Leu Lys Asp Ser Ile Met Leu Ala Leu Ser Phe same time 35 40 45 Ala Leu Tyr Leu Ala same time Ala Leu Ala gin Lys Phe Gly Ala Thr Tyr 50 55 60 Asp Ile Leu Phe Leu Glu for Ile Leu Ala for Leu same time Ser Lys Cys 65 70 75 80 Glu Ile Ala Leu wall Ser Glu Ser Met Asp Ile wall Met same time Glu Ser 85 90 95 Leu Ile same time Ser Phe Asp Ile Ala Leu Asp Tyr wall Tyr Gly Glu Ala 100 105 110 Lys Arg Ala Tyr Glu Glu Asp Ile Leu Ser His Ile Tyr gin Tyr Arg 115 120 125 Lys Gly same time Ala Ile Lys Ser Leu Lys Asp Lys same time Ile Phe Ile wall 130 135 140 Asp Arg Gly Ile Glu Thr Gly Phe Arg Ala Gly Leu Gly wall gin Thr 145 150 155 160 Cys Leu Lys Lys Glu Cys gin Asp Ile Tyr Ile Leu Thr for Ile Leu 165 170 175

303

Ala Gin Asn Val Ala Gin Le Glu Ser Glu Cys Asp Gly Val Ile 180 185 190 Ser wall Tyr Arg for Glu Cys Phe wall Ser wall Glu His His Tyr Lys 195 200 205 Glu Leu Lys Arg Leu Ser same time Glu Glu Ile Glu Lys Tyr Leu Gly Ala 210 215 220 same time same time Ala for same time Leu Lys Lys Glu His 225 230

(2) INFORMATION FOR SEQUENCE NO. 160:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 287 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULA TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix) SIGN (A) NAME / KEY: Differently letters (B) PLACEMENT 1. . . 287

(xi) SEQUENCE DESCRIPTION: Sequence £. 160:

Leu Lys gin Ser Glu Met Ala Met Glu Phe same time Asp for Arg Met Arg 1 5 10 15 Phe Phe Ile Gly Asp wall Arg Asp Leu Glu Arg Leu same time Tyr Ala Leu 20 25 30 Glu Gly wall Asp Ile Cys Ile His Ala Ala Ala Leu Lys His wall for 35 40 45 Ile Ala Glu Tyr same time for Leu Glu Cys Ile Lys Thr same time Ile Met Gly 50 55 60 Ala Ser same time wall Ile same time Ala Cys Leu Lys same time Glu Ile Ser gin wall 65 70 75 80 Ile Ala Leu Ser Thr Asp Lys Ala Ala same time for Ile same time Leu Tyr Gly 85 90 95 Ala Thr Lys Leu Cys Ser Asp Lys Leu Phe wall Ser Ala same time same time Phe 100 105 110 Lys Gly for Ser gin Thr gin Phe Gly wall wall Arg Tyr Gly same time wall

304

115 120 125 wall Gly Ser Arg Gly Ser wall wall for Phe Phe Lys Lys Leu wall gin 130 135 140 same time Lys Ala Ser Glu Ile for Ile Thr Asp Ile Arg Met Thr Arg Phe 145 150 155 160 Trp Ile Thr Leu Asp Glu Gly wall Ser Phe wall Leu Lys Ser Leu Lys 165 170 175 Arg Met His Gly Gly Glu Ile Phe wall for Lys Ile for Ser Met Lys 180 185 190 Met Ile Asp Leu Ala Lys Ala Leu Ala for same time Ile for Thr Lys Ile 195 200 205 Ile Gly Ile Arg for Gly Glu Lys Leu His Glu wall Met Ile for Lys 210 215 220 Asp Glu Ser His Leu Ala Leu Glu Phe Glu Asp Phe Phe Ile Ile gin 225 230 235 240 for Thr Ile Ser Phe gin Thr for Lys Asp Tyr Thr Leu Thr Lys Leu 245 250 255 His Glu Lys Gly gin Lys wall Ala for Asp Phe Glu Tyr Ser Ser His 260 265 270 Thr same time same time gin Trp Leu Glu for Asp Asp Leu Leu Lys Leu Leu 275 280 285

(2) INFORMATION FOR SEQUENCE NO. 161:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 201 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULAR TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) NAME / KEY: various characters (B) LOCATION 1 ... 201 (xi) SEQUENCE DESCRIPTION: Sequence no. 161:

Met Arg Leu His Thr Ala Phe Phe Gly Ile Asn Ser Leu Leu Val Ala 15 10 15

305

Thr Leu Leu White Ser Gly Cys Ser Leu Phe Lys Lys Arg Asn Thr Asn 20 25 30

Ala Gin Leu White Pro Pro Ser Ala Asn Gly Leu Gin Ala Pro White Tyr 35 40 45

Pro Pro Thr Asn Phe Thr Pro Arg Lys Ser ile Gin Pro Leu Pro Ser

55 60

Pro Arg Leu Glu Asn As Gn Asp Gin Pro Gn Ser Ser Asn Pro Thr

70

Asn Alai Pro Asn Thr Proi Leu Thr Pro Asn Asn Vali Glu

90 95

Leu Asn Ala Val Gly Met Gly Val Ala Pro Glu Ser Thr White Ser Pro

100 105 110

Ser Gin Ala Leu Ala Leu Ala Lys Arg Ala Ala White Val Asp Gly Tyr

115 120 125

Arg Gin Leu Gly Glu Lys Met Tyr Gly White Arg Val Asn Ala Gin Asp

129 135 140

Thr Val Lys Asp Met Val Leu Gin Asn Ser Val White Lys Thr Arg Val

145 150 155 160

Asn Ala Leu White Arg Asn Ala Glu White Thr Glu Thr White Tyr Lys Asp

165 170 175

Gly Leu Cys Gin Val Ser Met

180 185 190

Tyr Arg leu Ser Gly Ser Arg Gly

195 200 (2) INFORMATION FOR SEQUENCE NO. 162:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 355 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULA TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix) SIGN: (A) NAME / KEY: different characters (B) PLACEMENT 1 ... 355

(xi) SEQUENCE DESCRIPTION: SEQ ID NO. 162:

306

Met Ser Tyr Thr Ile same time Lys Arg Phe Ser wall Gly wall Gly Leu Arg 1 5 10 15 Gly Leu Tyr Ala Thr Gly Ser Phe same time same time Thr wall Tyr wall for Leu 20 25 30 Glu Gly Ala Ser wall Leu Ser Ala Glu gin Ile Leu same time Leu for same time 35 40 45 same time wall Phe Ala Asp gin wall for Ser same time Met Met Thr Leu Leu Gly 50 55 60 same time Ile Gly Tyr gin for Ala Leu same time Cys gin Lys Ala Gly Gly Asp 65 70 75 80 Met Ser Asp gin Ser Cys gin Glu Phe Tyr same time Gly Leu Lys Lys Ile 85 90 95 Met Gly Tyr Ser Gly Leu Ile Lys Ala Ser Ala same time Leu Tyr Gly Thr 100 105 110 Thr gin wall wall gin Lys Ser same time Gly gin Gly wall Ser Gly Gly Tyr 115 120 125 Arg wall Gly Ser Ser Leu Arg wall Phe Asp His Gly Met Phe Ser wall 130 135 140 wall Tyr same time Ser Ser wall Thr Phe same time Met Lys Gly Gly Leu wall Ala 145 150 155 160 Ile Thr Glu Leu Gly for Ser Leu Gly Ser wall Leu Thr Lys Gly Ser 165 170 175 Leu same time Ile same time wall Ser Leu for gin Thr Leu Ser Leu Ala Tyr Ala 180 185 190 His gin Phe Phe Lys Asp Arg Leu Arg wall Glu Gly wall Phe Glu Arg 195 200 205 Thr Phe Trp Ser gin Gly same time Lys Phe Leu wall Thr for Asp Phe Ala 210 215 220 same time Ala Thr Tyr Lys Gly Leu Ser Gly Thr wall Ala Ser Leu Asp Ser 225 230 235 240 Glu Thr Leu Lys Lys Met wall Gly Leu Ala same time Phe Lys Ser wall Met 245 250 255 same time Met Gly Ala Gly Trp Arg Asp Thr same time Thr Phe Arg Leu Gly wall 260 265 270 Thr Tyr Met Gly Lys Ser Leu Arg Leu Met Gly Ala Ile Asp Tyr Asp 275 280 285 gin Ala for Ser for gin Asp Ala Ile Gly Ile for Asp Ser same time Gly 290 295 300 Tyr Thr wall Ala Phe Gly Thr Lys Tyr same time Phe Arg Gly Phe Asp Leu 305 310 315 320 Gly wall Ala Gly Ser Phe Thr Phe Lys Ser same time Arg Ser Ser Leu Tyr 325 330 335 gin Ser for Thr Ile Gly gin Leu Arg Ile Phe Ser Ala Ser Leu Gly

307

340 345 350 Tyr Arg Trp 355 (2) INFORMATION FOR SEQUENCE NO. 163:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 587 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULA TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) TITLE / KEY: different characters

(B) LOCATION . . . 587 (Xi) SEQUENCE DESCRIPTION: Sequence no. 163: Met Lys same time Phe Ser for Leu Tyr Cys Leu Lys Lys Leu Lys Lys Arg 1 5 10 15 His Leu Ile Ala Leu Ser Leu for Leu Leu Ser Tyr Ala same time Gly Phe 20 25 30 Lys Ile gin Glu gin Ser Leu same time Gly Thr Ala Leu Gly Ser Ala Tyr 35 40 45 wall Ala Gly Ala Arg Gly Ala Asp Ala Ser Phe Tyr same time for Ala same time 50 55 60 Met Gly Phe Thr same time Asp Trp Gly Glu same time Arg Ser Glu Phe Glu Met 65 70 75 80 Thr Thr Thr wall Ile same time Ile for Ala Phe Ser Phe Lys wall for Thr 85 90 95 Thr same time gin Gly Leu Tyr Ser wall Thr Ser Leu Glu Ile Asp Lys Ser 100 105 110 gin gin same time Ile Leu Gly Ile Ile same time Thr Ile Gly Leu Gly same time Ile 115 120 125 Leu Lys Ala Leu Gly same time Thr Ala Ala Thr same time Gly Leu Ser gin Ala 130 135 140 Ile same time Arg wall gin Gly Leu Met same time Leu Thr same time gin Lys wall wall 145 150 155 160

308

Thr Leu Ala Ser Lys for Asp Thr gin Ile wall same time Gly Trp Thr Gly 165 170 175 Thr Thr same time Phe wall Leu for Lys Phe Phe Tyr Lys Thr Arg Thr His 180 185 190 same time Gly Phe Thr Phe Gly Gly Ser Phe Thr Ala for Ser Gly Leu Gly 195 200 205 Met Lys Trp same time Gly Lys Gly Gly Glu Phe Leu His Asp wall Phe Ile 210 215 220 Met Met wall Glu Leu Ala for Ser Met Ser Tyr Thr Ile same time Lys Arg 225 230 235 240 Phe Ser wall Gly wall Gly Leu Arg Gly Leu Tyr Ala Thr Gly Ser Phe 245 250 255 same time same time Thr wall Tyr wall for Leu Glu Gly Ala Ser wall Leu Ser Ala 260 265 270 Glu gin Ile Leu same time Leu for same time same time wall Phe Ala Asp gin wall for 275 280 285 Ser same time Met Met Thr Leu Leu Gly same time Ile Gly Tyr gin for Ala Leu 290 295 300 same time Cys gin Lys Ala Gly Gly Asp Met Ser Asp gin Ser Cys gin Glu 305 310 315 320 Phe Tyr same time Gly Leu Lys Lys Ile Met Gly Tyr Ser Gly Leu Ile Lys 325 330 335 Ala Ser Ala same time Leu Tyr Gly Thr Thr gin wall wall gin Lys Ser same time 340 345 350 Gly gin Gly wall Ser Gly Gly Tyr Arg wall Gly Ser Ser Leu Arg wall 355 360 365 Phe Asp His Gly Met Phe Ser wall wall Tyr same time Ser Ser wall Thr Phe 370 375 380 same time Met Lys Gly Gly Leu wall Ala Ile Thr Glu Leu Gly for Ser Leu 385 390 395 400 Gly Ser wall Leu Thr Lys Gly Ser Leu same time Ile same time wall Ser Leu for 405 410 415 gin Thr Leu Ser Leu Ala Tyr Ala His gin Phe Phe Lys Asp Arg Leu 420 425 430 Arg wall Glu Gly wall Phe Glu Arg Thr Phe Trp Ser gin Gly same time Lys 435 440 445 Phe Leu wall Thr for Asp Phe Ala same time Ala Thr Tyr Lys Gly Leu Ser 450 455 460 Gly Thr wall Ala Ser Leu Asp Ser Glu Thr Leu Lys Lys Met wall Gly 4 65 470 475 480 Leu Ala same time Phe Lys Ser wall Met same time Met Gly Ala Gly Trp Arg Asp 485 490 495 Thr same time Thr Phe Arg Leu Gly wall Thr Tyr Met Gly Lys Ser Leu Arg

500

505

510

309

Gly Ala Leu Met Ile Asp Tyr Asp Gin Ala Ser Pro Gin Asp Ala 515 520 525 Ile Gly Ile for Asp Ser same time Gly Tyr Thr wall Ala Phe Gly Thr Lys 530 535 540 Tyr same time Phe Arg Gly Phe Asp Leu Gly wall Ala Gly Ser Phe Thr Phe 545 550 555 560 Lys Ser same time Arg Ser Ser Leu Tyr gin Ser for Thr Ile Gly gin Leu 565 570 575 Arg Ile Phe Ser Ala Ser Leu Gly Tyr Arg Trp 580 585

(2) INFORMATION FOR SEQUENCE NO. 164:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 205 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULA TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) NAME / KEY: different characters (B) LOCATION 1 ... 205 (xi) SEQUENCE DESCRIPTION: Sequence £. 164:

Leu Ile Phe Arg Phe Phe Leu Ile Leu Ser Leu Leu Lys Gly wall Leu 1 5 10 15 Leu Ala Lys Lys Asp Trp same time Phe Phe Lys for Leu Glu for Thr Lys 20 25 30 Lys Tyr Phe Gly Ser Phe Lys Ile Gly Tyr Leu Tyr gin His Ala Glu 35 40 45 Thr Thr Lys Arg Phe for Ile Arg for Lys same time Arg for for Ile Leu 50 55 60 Met Asp Lys Ile Tyr His Asp Ala Ser Leu Gly Phe Asp Ala Gly Tyr 65 70 75 80 wall Leu Lys Lys Lys Ala Leu Leu Gly Gly Tyr Leu Asp Ala Gly Met 85 90 95 Gly Asp Ser Tyr Phe Met Ser Ala Gly Leu wall Ala Gly wall Arg Leu

310

100 105 110 Phe Lys Gly Trp wall Ile for Lys Ile Ala Leu Gly Tyr gin Leu gin 115 120 125 Ile Leu Gly Ala Lys Ile Asp Lys Tyr gin Phe same time Ile gin Ser Ala 130 135 140 wall Gly Ser wall Gly Leu Phe Phe same time Ala Ala Lys same time Phe Gly Leu 145 150 155 160 Ser Ile Glu Ala Arg Gly Gly Ile for Phe Tyr Phe Ile gin Ser Arg 165 170 175 Phe Ser Lys Ala Phe Gly Thr for Arg Leu same time Ile Tyr Ser wall Gly 180 185 190 Ile Thr Phe Thr Phe Tyr Asp Phe Thr Arg Phe Leu Gly 195 200 205

(2) INFORMATION FOR SEQUENCE NO. 165:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 253 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULA TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix) SIGN: (A) NAME / KEY: different characters (B) PLACEMENT 1 ... 253

(xi) SEQUENCE DESCRIPTION: SEQ ID NO. 165:

Leu Trp His Ala Ala Phe Ser wall Gly Glu Trp Gly Trp same time Gly Asp 1 5 10 15 Glu Ile for Tyr Arg Asp Cys Asp Glu Trp Gly Leu Asp Asp Phe Tyr 20 25 30 Gly wall Lys for Thr Asp Cys Ala Gly wall Leu Ser Phe Ala Arg Ser 35 40 45 His Arg Arg gin same time gin Ala wall Leu Ser Lys for Lys Ser Phe Arg 50 55 60 Met Lys Lys Ile Ala Phe Ile Leu Ala Leu Trp wall Gly Leu Leu Gly 65 70 75 80

311

Ala Phe Glu for Lys Lys Ser His 85 White Tyr Phe Gly Ala Met Val Gly 90 95 Leu Ala Pro wall Lys White Thr Pro Lys Pro Ala Ser Asp Ser Ser Tyr 100 105 110 Thr Ala Phe Leu Gly Ala Lys Gly Gly Tyr Gin Phe Phe Phe 115 120 125 Lys Ala Leu Ala Gly Glu Phe Ser Tyr Leu Met Ala ile Lys 130 135 140 For Thr Ala Leu His Thr White Asn Thr Ser Leu Leu Ser Leu Asn Met 145 150 155 160 Asp Leu Ser Asp Phe Tyr Thr Lys Tyr Lys Tyr Ser Phe Gly Val 165 170 175 Tyr Gly Gly Leu Gly White Gly Tyr Phe Tyr Gin Ser Asn His Leu Gly 180 185 190 Met Lys Asn Ser Ser Phe Met Gly Asr Gly Leu Phe Asn Val Gly 195 200 205 Gly Ser Thr Asp Arg His His Arg Val Glu Leu Gly Ala Lys 210 215 220 Pro Phe Ser Lys Thr Arg Asn Ser Phe Lys Asn Ser Phr Leu 225 230 235 240 Glu Ser Val Phe His Ala Ala Tyr Ser Tyr Met Phe 245 250 (2) INFORMATION FOR SEQUENCE NO. 166:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 412 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULAR TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) NAME / KEY: various characters (B) LOCATION 1 ... 412 (xi) SEQUENCE DESCRIPTION: Sequence no. 166:

Met Glu Ser Lys Thr Val Lys Thr Asn Lys Val Gly Lys Asn Thr

312

Glu Thr Ala same time Thr Glu Ala Ser Lys Glu Thr His Phe Lys gin Ala 20 25 30 Ser Ala Ile Thr same time Thr Leu Arg Ser Ile Gly Gly Ile Phe Thr Lys 35 40 45 Ile Ala Lys Lys wall Arg Glu Leu wall Lys Lys His for Lys Lys Ser 50 55 60 Ser wall Ala Leu wall wall Leu Thr His Ile Ala Cys Lys Arg Ala Lys 65 70 75 80 Glu Leu Asp Asp Lys wall gin Asp Lys Ser Lys gin Ala Glu Lys Glu 85 90 95 same time gin Ile same time Trp Trp Lys Tyr Ser Gly Leu Thr Ile Ala Ala Ser 100 105 110 Leu Leu Leu Ala Ala Cys Ser Thr Gly Asp Ile Asp Lys gin Ile Glu 115 120 125 Leu Glu gin Glu Lys Lys Glu Ala same time Lys Ser Gly Ile Lys Leu Glu 130 135 140 gin Glu Arg gin Lys Thr Glu gin Glu Arg gin Lys Thr same time Lys Ser 145 150 155 160 Glu Ile Glu Leu Glu gin Glu Arg gin Lys Thr same time Lys Ser Gly Ile 165 170 175 Glu Leu Ala same time Ser gin Ile Lys Ala Glu gin Glu Arg gin Lys Thr 180 185 190 Glu gin Glu Lys gin Lys Ala same time Lys Ser Glu Ile Glu Leu Glu gin 195 200 205 gin Lys gin Lys Thr Ile same time Thr gin Arg Asp Leu Ile Lys Glu gin 210 215 220 Lys Asp Phe Ile Lys Glu Thr Glu gin same time Cys gin Glu Lys His Gly 225 230 235 240 gin Leu Phe Ile Lys Lys Ala Arg Ile Lys Thr Gly Ile Thr Thr Gly 245 250 255 Ile Ala Ile Glu Ile Glu Ala Glu Cys Lys Thr for Lys for Ala Lys 260 265 270 Thr same time gin Thr for Ile gin for Lys His Leu for same time Ser Lys gin 275 280 285 for Arg Ser gin Arg Gly Ser Lys Ala gin Glu Leu Ile Ala Tyr Leu 290 295 300 gin Lys Glu Leu Glu Ser Leu for Tyr Ser gin Lys Ala Ile Ala Lys 305 310 315 320 gin wall Asp Phe Tyr Lys for Ser Ser Ile Ala Tyr Leu Glu Leu Asp 325 330 335 for Arg Asp Phe Lys wall Thr Glu Glu Trp gin Lys Glu same time Leu Lys 340 345 350 Ile Arg Ser Lys Ala gin Ala Lys Met Leu Glu Met Arg same time for gin

313

355 360 365 Ala His Leu for Thr Ser gin Ser Leu Leu Phe wall gin Lys Ile Phe 370 375 380 Ala Asp Ile same time Lys Glu Ile Glu Ala wall Ala same time Thr Glu Lys Lys 385 390 395 400 Thr Glu Lys Ala Gly Tyr Gly Tyr Ser Lys Arg Met 405 410

(2) INFORMATION FOR SEQUENCE NO. 167:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 149 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULA TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) NAME / KEY: various characters (B) LOCATION 1 ... 149 (xi) SEQUENCE DESCRIPTION: Sequence no. 167:

Leu same time Trp Glu His Leu Met Lys Lys Leu Ala Phe Ser Leu Leu Phe 1 5 10 15 Thr Gly Thr Phe Leu Gly Leu Phe Leu same time Ala Ser Asp Phe Lys Ser 20 25 30 Met Asp same time Lys gin Leu Leu Glu gin Ala Gly Lys wall Ala for Ser 35 40 45 Glu wall for Glu Phe Arg Thr Glu wall same time Lys Arg Leu Glu Ala Met 50 55 60 Lys Glu Glu Glu Arg gin Lys Tyr Lys Ala Asp Phe Lys Lys Ala Met 65 70 75 80 Asp Lys same time Leu Ala Ser Leu Ser gin Glu Asp Arg same time Lys Arg Lys 85 90 95 Lys Glu Ile Leu Glu wall Ile Ala same time Lys Lys Lys Thr Met Thr Met 100 105 110 Lys Glu Tyr Arg Glu Glu Gly Leu Asp Leu His Asp Cys Ala Cys Glu 115 120 125

314

Gly Lys Lys Lys Gly Lys Lys Lys

Ser His His

145 (2) INFORMATION FOR SEQUENCE NO. 168:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 204 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULA TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix) SIGN: (A) NAME / KEY: different characters (B) PLACEMENT 1 ... 204

(xi) SEQUENCE DESCRIPTION: SEQ ID NO. 168:

Met Gin Ala Val 1 Ile 5 Leu Ala Asn Gly Glu 10 Phe Pro Lys Ser Lys Lys 15 Cys Leu Asp Ile Leu gin same time Ala for Phe Leu Ile Ala Cys Asp Gly 20 25 30 Ala wall Ile Ser Leu His Ala Leu gin Phe Lys for Ser wall wall Ile 35 40 45 Gly Asp Leu Asp Ser Ile Asp Ser His Leu Lys Ala Leu Tyr same time for 50 55 60 Ile Arg wall Ser Glu gin Asp Ser same time Asp Leu Ser Lys Ala Phe Phe 65 70 75 80 Tyr Ala Leu same time Arg Gly Cys Asp Asp Phe Ile Phe Leu Gly Leu same time 85 90 95 Gly Lys Arg Glu Asp His Ala Leu Ala same time Thr Phe Leu Leu Leu Glu 100 105 110 Tyr Phe Lys Phe Cys Lys Lys Ile gin Ser wall Ser Asp Tyr Gly Leu 115 120 125 Phe Arg wall Leu Glu Thr for Phe Thr Leu for Ser Phe Lys Gly Glu 130 135 140 gin Ile Ser Leu Phe Ser Leu Asp Leu Lys Ala Arg Phe Thr Ser Lys

315

145 150 155 160 same time Leu Lys Tyr for Leu Lys Asp Leu Arg Leu Lys Thr Leu Phe Ser 165 170 175 Gly Ser Leu same time Glu Ala Thr same time His Cys Phe Ser Leu Ser Ser Glu 180 185 190 for Lys Ser wall wall Leu wall Tyr gin Lys Phe Ser 195 200

(2) INFORMATION FOR SEQUENCE NO. 169:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 280 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULA TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix) SIGN: (A) NAME / KEY: different characters (B) PLACEMENT 1 ... 280

(xi) SEQUENCE DESCRIPTION: SEQ ID NO. 169:

wall Phe Asp Ser Leu Gly Gly Phe Leu Gly Tyr Lys Thr Phe Lys for 1 5 10 15 Ile wall Asp Lys wall Lys same time Ile same time Ala Trp Ile Lys same time Tyr Asp 20 25 30 same time Lys Lys Ala gin Glu Ile Met Gly Phe Ile Glu same time for Thr for 35 40 45 Asp Phe gin same time same time Lys Phe Leu Cys wall Leu same time Arg gin Gly Thr 50 55 60 Arg His same time same time Tyr Leu Gly Leu Thr Ser Thr same time Leu Leu Ile Gly 65 70 75 80 Ala Ile Tyr Phe Ser Ile Arg His Cys Ile Lys Ala Thr Trp gin same time 85 90 95 Asp Arg Asp gin Phe Tyr Ala for Tyr Asp Asp Ala Phe gin Asp Asp 100 105 110 Ser Glu Phe Lys same time same time Cys Leu Ala Phe Met Leu Phe His Thr gin 115 120 125

316

Asn Arg 130 Ile Thr Ala Thr Gin Gly Thr 135 same time His Phe 140 Ile for Phe Ser Glu Asp Glu wall Asp Ser Lys Glu Arg Tyr Leu Ser His Ala Leu Leu 145 150 155 160

Asp Phe Leu Lys Glu White Lys Glu For Lys Lys Ser Asp Ser Leu

165 170 175

Phe Leu Asn Lys Lys Glu Asn Lys for Leu Lys Phe Ser 190 Ser Ser 180 185 Ala Ser Lys wall Phe Asp Ala Gly Arg Glu Ile Tyr Arg Tyr Tyr His 195 200 205 Thr gin Asp Phe Ile His Thr for Tyr same time Ala same time Ala Ser Leu Tyr 210 215 220 Asp Ile Lys Glu Phe Phe gin Gly Arg same time Lys gin Gly Arg Leu same time 225 230 235 240 Ser for Thr Lys Ala Lys Asp Glu Tyr Tyr Lys gin Leu Tyr Ala same time 245 250 255 Leu gin Tyr Ala Leu Lys Asp Leu Ala Lys Glu Ile gin for Lys wall 260 265 270 Tyr Glu Tyr Gly Phe Leu Arg Glu 275 280

(2) INFORMATION FOR SEQUENCE NO. 170:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 309 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULA TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix) SIGN: (A) NAME / KEY: different characters (B) PLACEMENT 1 ... 309

(xi) SEQUENCE DESCRIPTION: SEQ ID NO. 170:

Cys Asp Arg Ala White Pro His Trp Leu Phe Ser Leu Gly Tyr Arg Tyr 15 10 15

Pro Pro Pro Leu Lys Pro Thr Asn Ala Phe

317

25 30

Ser Leu Gly 35 Gly Phe Leu Thr Phe Lys 40 for 45 Val Val Asp Lys wall Lys same time Ile same time Ala Trp Ile Lys same time Tyr Asp same time Lys Lys 50 55 60 Ala gin Glu Ile Met Gly Phe Ile Glu same time for Thr for Asp Phe gin 65 70 75 80 same time same time Lys Phe Leu Cys wall Leu same time Arg gin Gly Thr Arg His same time 85 90 95 same time Tyr Leu Gly Leu Thr Ser Thr same time Leu Leu Ile Gly Ala Ile Tyr 100 105 110 Phe Ser Ile Arg His Cys Ile Lys Ala Thr Trp gin same time Asp Arg Asp 115 120 125 gin Phe Tyr Ala for Tyr Asp Asp Ala Phe gin Asp Asp Ser Glu Phe 130 135 140 Lys same time same time Cys Leu Ala Phe Met Leu Phe His Thr gin same time Arg Ile 145 150 155 160 Thr Ala Thr gin Gly Thr same time His Phe Ile for Phe Ser Glu Asp Glu 165 170 175 wall Asp Ser Lys Glu Arg Tyr Leu Ser His Ala Leu Leu Asp Phe Leu 180 185 190 Lys Gly Glu Ile Lys Glu for Lys Lys Ser Asp Ser Leu Phe Leu same time 195 200 205 Ala Lys Lys Glu same time Lys for Leu Lys Phe Ser Ser Ser Ala Ser Lys 210 215 220 wall Phe Asp Ala Gly Arg Glu Ile Tyr Arg Tyr Tyr His Thr gin Asp 225 230 235 240 Phe Ile His Thr for Tyr same time Ala same time Ala Ser Leu Tyr Asp Ile Lys 245 250 255 Glu Phe Phe gin Gly Arg same time Lys gin Gly Arg Leu same time Ser for Thr 260 265 270 Lys Ala Lys Asp Glu Tyr Tyr Lys gin Leu Tyr Ala same time Leu gin Tyr 275 280 285 Ala Leu Lys Asp Leu Ala Lys Glu Ile gin for Lys wall Tyr Glu Tyr 290 295 300 Gly Phe Leu Arg Glu

305 (2) INFORMATION FOR SEQUENCE NO. 171:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 187 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear

318 (ii) MOLECULA TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) NAME / KEY: various characters (B) LOCATION 1 ... 187 (xi) SEQUENCE DESCRIPTION: Sequence £. 171:

Leu Glu Thr Tyr Ile Ile Asp Ala Asp same time Ile Asp Gly Asp Leu Phe 1 5 10 15 Phe Tyr same time Leu Thr Arg same time Ser same time Asp Phe Ser Met Leu for wall 20 25 30 Phe Glu Leu Asp Arg Ile Ala gin Lys Ile Arg same time Ile Leu Lys Lys 35 40 45 His Gly Ser Arg Lys Asp Ile Ile Leu Lys His same time Glu Ile Lys Glu 50 55 60 Ala Phe Phe Ser for Phe Lys for gin Leu Lys Thr wall gin wall Phe 65 70 75 80 Leu Ser His Ser His Ala Asp Lys same time Lys Ala Leu Gly wall Lys Asp 85 90 95 Tyr Leu Glu Ser Lys Thr Lys Arg Lys wall Phe Ile Asp Ser Leu Phe 100 105 110 Trp Asp Tyr Lys Asp Asp wall Leu same time Lys Leu Ala Lys His Asp Asp 115 120 125 Ile Ser Lys Ile Glu Asp Ala Phe Thr Leu Ile Leu Arg Lys Ser Leu 130 135 140 gin Asp Met Ile Glu Lys Cys for Tyr Phe wall Phe Leu gin Ser Lys 145 150 155 160 same time Ser wall Ser same time gin Gly Leu Ser Arg Ile Thr Tyr Ser Ala Trp 165 170 175 Ile Tyr Glu Glu Leu Lys Ile Ala Ser Phe Tyr

180 185 (2) INFORMATION FOR SEQUENCE NO. 172:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 198 amino acids (B) TYPE: amino acid

319 (D, TOPOLOGY: linear (ii) MOLECULA TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix) SIGN: (A, NAME / KEY: different characters (B) PLACEMENT 1 ... 198

(xi, SEQUENCE DESCRIPTION: SEQ ID NO 172:

Leu Glu Thr Tyr Ile Ile Asp Ala Asp same time Ile Asp Gly Asp Leu Phe 1 5 10 15 Phe Tyr same time Leu Thr Arg same time Ser same time Asp Phe Ser Met Leu for wall 20 25 30 Phe Glu Leu Asp Arg Ile Ala gin Lys Ile Arg same time Ile Leu Lys Lys 35 40 45 His Gly Ser Arg Lys Asp Ile Ile Leu Lys His same time Glu Ile Lys Glu 50 55 60 Ala Phe Phe Ser for Phe Lys for gin Leu Lys Thr wall gin wall Phe 65 70 75 80 Leu Ser His Ser His Ala Asp Lys same time Lys Ala Leu Gly wall Lys Asp 85 90 95 Tyr Leu Glu Ser Lys Thr Lys Arg Lys wall Phe Ile Asp Ser Leu Phe 100 105 110 Trp Asp Tyr Lys Asp Asp wall Leu same time Lys Leu Ala Lys His Asp Asp 115 120 125 Ile Ser Lys Ile Glu Asp Ala Phe Thr Leu Ile Leu Arg Lys Ser Leu 130 135 140 gin Asp Met Ile Glu Lys Cys for Tyr Phe wall Phe Leu gin Ser Lys 145 150 155 160 same time Ser wall Ser same time gin Gly Leu Ser Arg Ile Thr Tyr Ser Ala Trp 165 170 175 Ile Tyr Glu Glu Leu Lys Ile Ala Ser Phe Leu Leu Ala Leu Leu Thr 180 185 190 Arg wall Ala gin Phe gin 195

(2) INFORMATION FOR SEQUENCE NO. 173

320 (i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 189 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULA TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix) SIGN (A) NAME / KEY: different characters (B) PLACEMENT 1 ... 189

(xi) SEQUENCE DESCRIPTION: SEQ ID NO. 173:

Met 1 Met Thr Lys Asn Ala Tyr Ala Phe Val Val White Glu Lys Ser White 5 10 15 Met wall Phe Lys Cys Ala Lys Asp Lys Gly Leu Ile for Ile Thr Glu 20 25 30 Gly Phe wall for Leu Lys Glu Gly Phe Leu Arg Ser Phe Lys Glu Arg 35 40 45 Cys same time Leu Asp Phe Leu Glu same time Leu Asp Leu Leu Phe Leu Tyr Asp 50 55 60 Tyr gin Phe for Ser Glu wall Phe Ser Leu Cys Lys Asp Leu Lys same time 65 70 75 80 Ser Ile Trp Asp Arg Lys Leu wall wall wall Leu wall Glu Ala Leu Glu 85 90 95 Gly Phe Lys Gly Leu same time Leu Ser Leu Lys Ile Glu Asp Arg His Ser 100 105 110 same time Ser Leu Gly same time Gly wall gin Lys Leu Leu Thr same time Ala Asp Leu 115 120 125 Gly Ser same time His Lys for Ile wall Ile Asp Ser Met Lys Thr Tyr His 130 135 140 gin Ser gin gin Glu Lys Tyr Lys Arg Glu Arg Gly Glu Thr Leu Glu 145 150 155 160 wall Arg for Thr Thr for for Ser Tyr Gly Gly Gly Ser Ile Arg Ile 165 170 175 Ser Gly Asp Lys Lys for Asp Ser same time Glu Glu same time Phe

180 185 (2) INFORMATION FOR SEQUENCE NO. 174:

321 (i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 590 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULA TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) NAME / KEY: various characters (B) LOCATION 1 ... 590 (xi) SEQUENCE DESCRIPTION: Sequence no. 174:

Met Lys Ala Ile Lys Ile Leu Leu 1 Ile Ser wall same time 5 Arg Ala Leu Phe Gly Glu Leu 20 Thr for Lys Ile wall Thr Thr 35 Glu Trp Gly Ala Thr 40 Ala Gly 50 Asp Ala Lys Lys Phe 55 Ser Ala 65 Ser Gly Ile Leu Gly 70 same time Phe Arg Leu Lys Leu gin 85 Lys same time Leu Lys Asp Ser Phe 100 Tyr Ser Tyr Arg Thr Ser Leu 115 Lys Asp gin Lys Thr 120 Ala wall 130 wall Gly Ala Tyr Leu 135 Lys Lys 145 Ser for Tyr Tyr Arg 150 Ser same time same time Tyr Tyr Gly Met 165 Tyr Gly Met Tyr Gly Met Gly 180 Met Tyr Asp Phe Tyr

Ile Met 10 Thr Leu Ser Leu same time 15 Ala Asp 25 Leu Lys Asp Ser gin 30 Leu Lys Asp Phe Gly Gly Tyr 45 Lys Ser same time Leu same time Tyr Ile 60 same time Ala Ala same time Leu wall Glu 75 Lys Met Arg Phe same time 80 Ala His 90 Ala His Leu Arg gin 95 Ala Tyr 105 Cys Leu Lys Ile Ile 110 Ala Arg Gly Ile Tyr Ile for 125 Leu Gly Ile gin Lys Met Leu 140 Ala Asp Leu Ser gin gin Glu 155 same time Glu Lys Ala gin 160 Tyr Tyr 170 same time Ser Tyr Tyr Ser 175 for Gly 185 Met Gly Met Tyr Gly 190 Met Tyr Asp Phe Tyr Asp Gly Met Tyr Gly

322

195 200 205

Phe Tyr for Asn Met Phe Phe Met Gin Val Gin Asp Tyr Leu Met 210 215 220 Leu Glu same time Tyr Met Tyr Ala Leu Asp gin Glu Glu Ile Leu Asp His 225 230 235 240 Asp Ala Ser Ile same time gin Leu Asp Thr for Thr Asp Asp Asp Arg Asp 245 250 255 Asp Lys Asp Asp Lys Ser Ser gin for Ala same time Leu Met Ser Phe Tyr 260 265 270 Arg Asp for Lys Phe Ser Lys Asp Ile gin Thr same time Arg Leu same time Ser 275 280 285 Ala Leu wall same time Leu Asp same time Ser His Met Leu Lys Asp same time Ser Leu 290 295 300 Phe His Thr Lys Ala Met for Thr Lys Ser wall Asp Ala Ile Thr Ser 305 310 315 320 gin Ala Lys Glu Leu same time His Leu wall Gly gin Ile Lys Glu Met Lys 325 330 335 gin Asp Gly Ala Ser for same time Lys Ile Asp Ser wall wall same time Lys Ala

340 345 350

Met Glu Val Arg Asp Lys Leu Asp Asn Asn Leu Asn Gin Leu Asp Asn 355 360 365

Asp Leu Lys Asp Ser Glu Lys Ser Ser Glu Gin Ala Gin Val 370 375 380

Asp Lys Ala Leu His Ser Ser Asp Asp

385 390 395 400

Val Gly Asn Tyr Leu Asp Gly Ser Leu Lys Clay Asp Gly Asp Asp Arg

405 410 415

Asp Asp Leu Asn 420 Asp Ala Asn Asn Pro Met Gin gin 425 430 gin Thr for Ile same time same time Met Asp same time Thr His Ala same time Asp Ser Lys 435 440 445 Asp gin Gly Gly same time Ala Leu Ile same time for same time same time Ala Thr same time Asp 450 455 4 60 Asp His same time Asp Asp His Met Asp Thr same time Thr Thr Asp Thr Ser same time 465 470 475 480 Ala same time Asp Thr for Thr Asp Asp Lys Asp Ala Ser Gly same time same time Thr 485 490 495 Gly Asp Met same time same time Thr Asp Thr Gly same time Thr Asp Thr Gly same time Thr 500 505 510 Asp Thr Gly same time Thr Asp Asp Met Ser same time Met same time same time Gly same time Asp 515 520 525 Asp Thr Gly same time Thr same time Asp Asp Met Gly same time Ser same time Asp Met Gly 530 535 540 Asp Asp Met same time same time Ala same time Asp Met same time Asp Asp Met Gly same time Ser

323

545 550 555 560

Asp Asp Gly Asp Asp Asp Gly Asp Asp

565 570 575

Asp Met Gly Asp Met Gly Asp Met Gly Asp Met Gly Asn

580 585 590 (2) INFORMATION FOR SEQUENCE NO. 175:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 195 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULA TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) TITLE / KEY: different characters

(B) LOCATION ... 195 (Xi) SEQUENCE DESCRIPTION: Seq. 175: Leu Asn Leu Arg Leu Ala Gly Ala Ser Val Leu Thr 1 5 10 15 Ser Gly Cys Phe Phu Leu Lys Met Phe Asp Lys Leu Ser Ser Asn 20 25 30 Asp Trp His clay Gin Lys Val Glu Met Asn His Gin Val Tyr Asp 35 40 45 Glu Thr Met Leu Ala, Asp Ser Ala Phe Arg Glu Glu Glu Glu Glu 50 55 60 Asp Ser Ser Leu Asn Thr Ala Leu For Glu Asp Lys Thr Ala and Glu 65 70 75 80 Ala Lys Glu Gin Glu Lys Arg His Trp Tyr Glu Leu 85 90 95 Phe Lys Lys Pro Lys Pro Lys Pro Lys Ser G Met Gly Glu Phe Val Phe 100 105 110 Asp Gin Lys Glu Asn Arg ile Tyr Gly Lys Gly Tyr 115 120 125 Phe Ala Ser Tyr Thr Gly Asp Arg His White Ala White Glu Asp 130 135 140

324

Ser Gly Ile Ser Arg Lys wall Cys Arg Asp Glu His Leu Met Ala Phe 145 150 155 160 Glu Leu Glu Phe Met Glu same time Phe Lys Gly same time Phe Ala wall Thr Lys 165 170 175 Gly Lys Asp Thr Leu Ile Leu Asp same time gin Lys Met Lys Ile Tyr Leu 180 185 190

Lys Thr Pro 195 (2) SEQ ID NO. 176:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 744 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULA TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) NAME / KEY: various characters (B) LOCATION 1 ... 744 (xi) SEQUENCE DESCRIPTION: Sequence no. 176:

Met Leu Lys Leu Ala Ser Lys Thr Ile Cys Leu Ser Leu Ile Ser Ser 1 5 10 15 Phe Thr Ala wall Glu Ala Phe gin Lys His gin Lys Asp Gly Phe Phe 20 25 30 Ile Glu Ala Gly Phe Glu Thr Gly Leu Leu gin Gly Thr gin Thr gin 35 40 45 Glu gin Thr Ile Ala Thr Thr gin Glu Lys for Lys for Lys for Lys 50 55 60 for Lys for Ile Thr for gin Ser Thr Tyr Gly Lys Tyr Tyr Ile Ser 65 70 75 80 gin Ser Thr Ile Leu Lys same time Ala Thr Glu Leu Phe Ala Glu Asp same time 85 90 95 Ile Thr same time Leu Thr Phe Tyr Ser gin same time for wall Tyr wall Thr Ala 100 105 110 Tyr same time gin Glu Ser Ala Glu Glu Ala Gly Tyr Gly same time same time Ser Leu

325

Ile Met Ile gin same time Phe Leu for Tyr same time Leu same time same time Ile Glu Leu 130 135 140 Ser Tyr Thr Asp Asp gin Gly same time wall wall Ser Leu Gly wall Ile Glu 145 150 155 160 Thr Ile for Lys gin Ser gin Ile Ile Leu for Ala Ser Leu Phe same time 165 170 175 Asp for gin Leu same time Ala Asp Gly Phe gin gin Leu gin Thr same time Thr 180 185 190 Thr Arg Phe Ser Asp Ala Ser Thr gin same time Leu Phe same time Lys Leu Ser 195 200 205 Lys wall Thr Thr same time Leu gin Met Thr Tyr Ile same time Tyr same time gin Phe 210 215 220 Ser Ser Gly same time Gly Ser Gly Ser Lys for for Cys for for Tyr Glu 225 230 235 240 same time gin Ala same time Cys wall Ala Lys wall for for Phe Thr Ser gin Asp 245 250 255 Ala Lys same time Leu Thr same time Leu Met Leu same time Met Met Ala wall Phe Asp 260 265 270 Ser Lys Ser Trp Glu Asp Ala wall Leu same time Ala for Phe gin Phe Ser 275 280 285 Asp same time same time Leu Ser Ala for Cys Tyr Ser Asp Tyr Leu Thr Cys wall 290 295 300 same time for Tyr same time Asp Gly Leu wall Asp for Lys Leu Ile Ala Lys same time 305 310 315 320 Lys Gly Asp Glu Tyr same time Ile Glu same time Gly gin Thr Gly Ser wall Ile 325 330 335 Leu Thr for gin Asp wall Ile Tyr Ser Tyr Arg wall Ala same time same time Ile 340 345 350 Tyr wall same time Leu Leu for Thr Arg Gly Gly Asp Leu Gly Leu Gly Ser 355 360 365 gin Tyr Gly Gly for same time Gly for Gly Asp Asp Gly Thr same time Phe Gly 370 375 380 Ala Leu Gly Ile Leu Ser for Phe Leu Asp for Glu Ile Leu Phe Gly 385 390 395 400 Lys Glu Leu same time Lys wall Ala Ile Met gin Leu Arg Asp Ile Ile His 405 410 415 Glu Tyr Gly His Thr Leu Gly Tyr Thr His same time Gly same time Met Thr Tyr 420 425 430 gin Arg wall Arg Met Cys Glu Glu same time same time Gly for Glu Glu Arg Cys 435 440 445 gin Gly Gly Arg Ile Glu gin wall Asp Gly Lys Glu wall gin wall Phe 450 455 460 Asp same time Gly His Glu wall Arg Asp Thr Asp Gly Ser Thr Tyr Asp wall

326

(+420) 465 470 475 480

Cys Ser Arg Phe Lys Asp Lys Pro Tyr Thr Ala Gly Ser Tyr For Asn 485 490 495 Ser Ile Tyr Thr Asp Cys Ser gin wall for Ala Gly Leu Ile Gly wall 500 505 510 Thr Ser Ala wall Trp gin gin Leu Ile Asp gin same time Ala Leu for wall 515 520 525 Asp Phe Thr same time Leu Ser Ser gin Thr same time Tyr Leu same time Ala Ser Leu 530 535 540 same time Thr gin Asp Phe Ala Thr Thr Met Leu Ser Ala Ile Ser gin Ser 545 550 555 560 Leu Ser Ser Ser Lys Ser Ser Ala Thr Thr Tyr Arg Thr Ser Lys Thr 565 570 575 Ser Arg for Phe Gly Ala for Leu Leu Gly wall same time Leu Lys Met Gly 580 585 590 Tyr gin Lys Tyr Phe same time Asp Tyr Leu Gly Leu Ser Ser Tyr Gly Ile 595 600 605 Ile Lys Tyr same time Tyr Ala gin Ala same time same time Glu Lys Ile gin gin Leu 610 615 620 Ser Tyr Gly wall Gly Met Asp wall Leu Phe Asp Phe Ile Thr same time Tyr 625 630 635 640 Thr same time Glu Lys same time for Lys Ser same time Leu Thr Lys Lys wall Phe Thr 645 650 655 Ser Ser Leu Gly wall Phe Gly Gly Leu Arg Gly Leu Tyr same time Ser Tyr 660 665 670 Tyr Leu Leu same time gin Tyr Lys Gly Ser Gly same time Leu same time wall Thr Gly 675 680 685 Gly Leu same time Tyr Arg Tyr Lys HLS Ser Lys Tyr Ser Ile Gly Ile Ser 690 695 700 wall for Leu wall gin Leu Lys Ser Arg Ile wall Ser Ser Asp Gly Ala 705 710 715 720 Tyr Thr same time Ser Ile Thr Leu same time Glu Gly Gly Ser His Phe Lys wall 725 730 735 Phe Phe same time Tyr Gly Trp Ile Phe

740 (2) INFORMATION FOR SEQUENCE NO. 177:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 529 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULA TYPE: protein

327 (iii) HYPOTHETICAL: YES

(vi) ORIGINAL SOURCE: Helicobacter pylori (A) ORGANISM: (Ix) SIGN: (A) TITLE / KEY: different characters (B) LOCATION 1 ... 528

(xi) SEQUENCE DESCRIPTION: SEQ ID NO. 177:

Met Thr Tyr Ile same time Tyr same time gin Phe Ser Ser Gly same time Gly Ser Gly 1 5 10 15 Ser Lys for for Cys for for Tyr Glu same time gin Ala same time Cys wall Ala 20 25 30 Lys wall for for Phe Thr Ser gin Asp Ala Lys same time Leu Thr same time Leu 35 40 45 Met Leu same time Met Met Ala wall Phe Asp Ser Lys Ser Trp Glu Asp Ala 50 55 60 wall Leu same time Ala for Phe gin Phe Ser Asp same time same time Leu Ser Ala for 65 70 75 80 Cys Tyr Ser Asp Tyr Leu Thr Cys wall same time for Tyr same time Asp Gly Leu 85 90 95 wall Asp for Lys Leu Ile Ala Lys same time Lys Gly Asp Glu Tyr same time Ile 100 105 110 Glu same time Gly gin Thr Gly Ser wall Ile Leu Thr for gin Asp wall Ile 115 120 125 Tyr Ser Tyr Arg wall Ala same time same time Ile Tyr wall same time Leu Leu for Thr 130 135 140 Arg Gly Gly Asp Leu Gly Leu Gly Ser gin Tyr Gly Gly for same time Gly 145 150 155 160 for Gly Asp Asp Gly Thr same time Phe Gly Ala Leu Gly Ile Leu Ser for 165 170 175 Phe Leu Asp for Glu Ile Leu Phe Gly Lys Glu Leu same time Lys wall Ala 180 185 190 Ile Met gin Leu Arg Asp Ile Ile His Glu Tyr Gly His Thr Leu Gly 195 200 205 Tyr Thr His same time Gly same time Met Thr Tyr gin Arg wall Arg Met Cys Glu 210 215 220 Glu same time same time Gly for Glu Glu Arg Cys gin Gly Gly Arg Ile Glu gin 225 230 235 240 wall Asp Gly Lys Glu wall gin wall Phe Asp same time Gly His Glu wall Arg

245

328

Asp Thr Asp Gly 260 Ser Thr Tyr Asp Cys Ser Phe Lys Asp Lys 265 270 for Tyr Thr Ala Gly Ser Tyr for same time Ser Ile Tyr Thr Asp Cys Ser 275 280 285 gin wall for Ala Gly Leu Ile Gly wall Thr Ser Ala wall Trp gin gin 290 295 300 Leu Ile Asp gin same time Ala Leu for wall Asp Phe Thr same time Leu Ser Ser 305 310 315 320 gin Thr same time Tyr Leu same time Ala Ser Leu same time Thr gin Asp Phe Ala Thr 325 330 335 Thr Met Leu Ser Ala Ile Ser gin Ser Leu Ser Ser Ser Lys Ser Ser 340 345 350 Ala Thr Thr Tyr Arg Thr Ser Lys Thr Ser Arg for Phe Gly Ala for 355 360 365 Leu Leu Gly wall same time Leu Lys Met Gly Tyr gin Lys Tyr Phe same time Asp 370 375 380 Tyr Leu Gly Leu Ser Ser Tyr Gly Ile Ile Lys Tyr same time Tyr Ala gin 385 390 395 400 Ala same time same time Glu Lys Ile gin gin Leu Ser Tyr Gly wall Gly Met Asp 405 410 415 wall Leu Phe Asp Phe Ile Thr same time Tyr Thr same time Glu Lys same time for Lys 420 425 430 Ser same time Leu Thr Lys Lys wall Phe Thr Ser Ser Leu Gly wall Phe Gly 435 440 445 Gly Leu Arg Gly Leu Tyr same time Ser Tyr Tyr Leu Leu same time gin Tyr Lys 450 455 460 Gly Ser Gly same time Leu same time wall Thr Gly Gly Leu same time Tyr Arg Tyr Lys 465 470 475 480 His Ser Lys Tyr Ser Ile Gly Ile Ser wall for Leu wall gin Leu Lys 485 490 495 Ser Arg Ile wall Ser Ser Asp Gly Ala Tyr Thr same time Ser Ile Thr Leu 500 505 510 same time Glu Gly Gly Ser His Phe Lys wall Phe Phe same time Tyr Gly Trp Ile 515 520 525

Phe (2) INFORMATION FOR SEQUENCE NO. 178:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 187 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear

329 (ii) MOLECULA TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) NAME / KEY: various characters (B) LOCATION 1 ... 187 (xi) SEQUENCE DESCRIPTION: Sequence no. 178:

Leu Gly Cys wall Ser Met Thr Leu Gly Ile Asp Glu Ala Gly Arg Gly 1 5 10 15 Cys Leu Ala Gly Ser Leu Phe wall Ala Gly wall wall Cys same time Glu Lys 20 25 30 Ile Ala Leu Glu Phe Leu Lys Met Gly Leu Lys Asp Ser Lys Lys Leu 35 40 45 Ser for Lys Lys Arg Phe Phe Leu Glu Asp Lys Ile Lys Thr His Gly 50 55 60 Glu wall Gly Phe Phe wall wall Lys Lys Ser Ala same time Glu Ile Asp His 65 70 75 80 Leu Gly Leu Gly Ala Cys Leu Lys Leu Ala Ile Glu Glu Ile wall Glu 85 90 95 same time Gly Cys Ser Leu Ala same time Glu Ile Lys Ile Asp Gly same time Thr Ala 100 105 110 Phe Gly Leu same time Lys Arg Tyr for same time Ile gin Thr Ile Ile Lys Gly 115 120 125 Asp Glu Thr Ile Ala gin Ile Ala Met Ala Ser wall Leu Ala Lys Ala 130 135 140 Ser Lys Asp Arg Glu Met Leu Glu Leu His Ala Leu Phe Lys Glu Tyr 145 150 155 160 Gly Trp Asp Lys same time Cys Gly Tyr Gly Thr Lys gin His Ile Glu Ala 165 170 175 Ile same time Lys Leu Gly Ala Thr Leu Ser Ser Ala

180 185 (2) INFORMATION FOR SEQUENCE NO. 179:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 204 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear

330

(Ii) MOLECULA TYPE: protein (Iii) HYPOTHETICAL: YES (Vi) ORIGINAL SOURCE: (A) ORGANISM: Helicobacter pylori (Ix) SIGN: (A) TITLE / KEY: different characters (B) LOCATION 1 ... 204 (Xi) SEQUENCE DESCRIPTION: Seq. 179:

Met Thr Leu Gly Ile Asp Glu Ala Gly Arg Gly Cys Leu Ala Gly Ser 1 5 10 15 Leu Phe wall Ala Gly wall wall Cys same time Glu Lys Ile Ala Leu Glu Phe 20 25 30 Leu Lys Met Gly Leu Lys Asp Ser Lys Lys Leu Ser for Lys Lys Arg 35 40 45 Phe Phe Leu Glu Asp Lys Ile Lys Thr His Gly Glu wall Gly Phe Phe 50 55 60 wall wall Lys Lys Ser Ala same time Glu Ile Asp His Leu Gly Leu Gly Ala 65 70 75 80 Cys Leu Lys Leu Ala Ile Glu Glu Ile wall Glu same time Gly Cys Ser Leu 85 90 95 Ala same time Glu Ile Lys Ile Asp Gly same time Thr Ala Phe Gly Leu same time Lys 100 105 110 Arg Tyr for same time Ile gin Thr Ile Ile Lys Gly Asp Glu Thr Ile Ala 115 120 125 gin Ile Ala Met Ala Ser wall Leu Ala Lys Ala Ser Lys Asp Arg Glu 130 135 140 Met Leu Glu Leu His Ala Leu Phe Lys Glu Tyr Gly Trp Asp Lys same time 145 150 155 160 Cys Gly Tyr Gly Thr Lys gin His Ile Glu Ala Ile same time Lys Leu Gly 165 170 175 Ala Thr for Phe His Arg His Ser Phe Thr Leu Lys same time Arg Ile Leu 180 185 190 same time for Lys Leu Leu Glu wall Glu gin Arg Leu wall 195 200

(2) INFORMATION FOR SEQUENCE NO. 180:

(i) SEQUENCE CHARACTERISTICS

331 (A) LENGTH: 192 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULA TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) TITLE / KEY: various characters (B) LOCATION 1 ... 192 (xi) SEQUENCE DESCRIPTION: Seq. 180:

Met 1 same time Ala Leu Lys 5 Lys Leu Ser Leu Phe Ala gin 20 Thr wall His Ala Tyr for Asp 35 Trp Leu Lys Ile same time 40 same time gin 50 Tyr wall Gly Ser Ala 55 Ser Tyr 65 Ser same time Tyr Ile for 70 Tyr Asp Ala Glu Glu Ile Ala 85 Leu Leu Arg Leu Glu Ser Ala 100 Leu Leu Thr Lys Leu gin wall 115 Lys same time same time wall Ile 120 Phe Leu 130 Thr Ser Lys Ser Ile 135 Leu same time 145 His Arg wall Tyr wall 150 Met wall Asp Leu Ile Ala Tyr 165 Phe Lys Ala Ser Ala Thr same time Leu Ser Ala Ile

180 (2) INFORMATION FOR SEQUENCE NO.

Phe Cys 10 Ala Leu Leu Ser Leu 15 Gly gin 25 His Leu Lys Asp Thr 30 Ile same time Leu Phe Asp Lys Lys 45 same time for for Ile Ser Gly Lys 60 Arg same time Asp Phe Asp Lys Leu 75 for for Glu Lys same time 80 Ala Arg 90 Met same time Ala Tyr Ser 95 Thr Met 105 Cys same time Arg Ile wall 110 Lys Ala Ser His Leu Phe Gly 125 Phe wall Asp Ala Lys Arg Phe 140 wall Asp Thr Thr gin Phe for 155 Phe Ile gin for Glu 160 Lys Arg 170 Ile Asp Leu Ser Leu 175 Ala Leu 185 181: same time Lys Ala Leu Phe 190 His Leu

332 (i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 86 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULA TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) NAME / KEY: various characters (B) LOCATION 1 ... 86 (xi) SEQUENCE DESCRIPTION: Sequence no. 181:

Met same time Ala Leu Lys Lys Leu Ser Phe Cys Ala Leu Leu Ser Leu Gly 1 5 10 15 Leu Phe Ala gin Thr wall His Ala gin His Leu Lys Asp Thr Ile same time 20 25 30 Tyr for Asp Trp Leu Lys Ile same time Leu Phe Asp Lys Lys same time for for 35 40 45 same time gin Tyr wall Gly Ser Ala Ser Ile Ser Gly Lys Arg same time Asp Phe 50 55 60 Tyr Ser same time Tyr Ile for Tyr Asp Asp Lys Leu for for Glu Arg Thr 65 70 75 80 Leu Lys Lys Ser Leu Phe 85

(2) INFORMATION FOR SEQUENCE NO. 182:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 75 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULA TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori

333 (ix) SIGN:

(A) NAME / KEY: different characters (B) LOCATION 1 ... 75 (xi) SEQUENCE DESCRIPTION: Sequence £. 182:

Leu Lys Ile Leu Thr Leu Phe Leu Ile Gly Leu same time Ala Leu Phe Ala 1 5 10 15 Leu Asp Leu same time Ala Leu Lys Thr Glu Ile Lys Glu Thr Tyr Leu Lys 20 25 30 Glu Tyr Lys Asp Leu Lys Leu Glu Ile Glu Thr Ile same time Leu Glu Ile 35 40 45 for Glu Arg Phe Ser His Ala Ser Ile Leu Ser Tyr Glu Leu same time Ala 50 55 60 Ser same time Lys Leu Lys Lys Asp Gly Ser Cys Phe 65 70 75

(2) INFORMATION FOR SEQUENCE NO. 183:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 211 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULA TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix) SIGN (A) NAME / KEY: different characters (B) PLACEMENT 1 ... 211

(xi) SEQUENCE DESCRIPTION: SEQ ID NO. 183:

Met Phe Ser Ile Ile Leu Gly Gly Gly Gly Gly same time Thr for Cys Gly 1 5 10 15 Leu Thr Trp gin His Phe Lys Leu Gly Asp Leu Phe Glu Ile Glu Lys 20 25 30 Thr Leu Ser Phe same time Lys Asp Ala Leu Thr gin Gly gin Asp Tyr Asp 35 40 45

334

Thr Thr Arg Thr Ser Gin Asn Gin Gly Val Leu Gin Thr Thr 50 55 60 Phe wall same time Ala Glu same time Leu same time for for Phe Thr Trp Ser Leu 65 70 75 Leu Leu gin Met Asp Phe Phe Tyr Arg Lys Lys Ser Trp Tyr Ala 85 90 95 gin Phe Met Arg Lys Ile Thr for Lys Thr Glu Ile Lys same time Lys 100 105 110 same time Ser Arg Ile Ala His Tyr Phe Thr Thr Leu Leu same time Ala Leu 115 120 125 Arg for Leu Leu Ser wall Leu wall Arg Asp Ile Asp Lys Thr Phe 130 135 140 Glu gin Lys Ile gin Leu for Leu Lys for Thr Ala Lys Thr gin 145 150 155 Leu Asp Gly Ile Asp Phe Asp Phe Met His Thr Leu Ile same time Ala 165 170 175 Met Lys gin Thr Ile gin Gly wall wall gin Tyr Cys Asp Ala Lys 180 185 190 gin Ala Thr Lys Glu wall Ile Ser gin Glu Thr for Ile gin Lys

200

205

Gly

Gly

Gly ile

Lys

Arg

Ser

160

Leu ile

Asp

195

Ser Leu Phe

210 (2) INFORMATION FOR SEQUENCE NO. 184:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 406 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULA TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix) SIGN (A) NAME / KEY: different characters (B) PLACEMENT 1 ... 406

(xi) SEQUENCE DESCRIPTION: SEQ ID NO. 184:

Gly Leu Ser Gin Leu Asn Ala Lys Trp Gly Glu

335 ίο

Phe Lys Leu Gly Asp Leu Phe Glu Ala Ser same time Gly Asp Phe Asp Ile 20 25 30 gin Lys Arg His Ile same time His Lys Gly Glu Phe wall Ile Thr Ala Gly 35 40 45 Leu Ser same time same time Gly wall Leu Gly gin Ser Asp Ile Lys Ala Lys wall 50 55 60 Phe Glu Ser His Thr Ile Thr Ile Asp Met Phe Gly Cys Ala Phe Tyr 65 70 75 80 Arg Ser Phe Ala Tyr Lys Met wall Thr His Ala Arg wall Phe Ser Leu 85 90 95 Lys for Lys Phe Glu Ile same time His Lys Ile Gly Leu Phe Leu Ser Thr 100 105 110 Leu Phe Phe Gly Tyr His Lys Lys Phe Gly Tyr Glu same time Met Cys Ser 115 120 125 Trp Ala Lys Ile Lys same time Asp Lys wall Ile Leu for Leu Lys for Thr 130 135 140 Ala same time Thr gin Thr Leu Glu Gly Ile Asp Phe Asp Phe Met Glu Lys 145 150 155 160 Phe Ile Ala Glu Leu Glu gin Cys Arg Leu Ala Glu Leu gin Ala Tyr 165 170 175 Leu Lys Ala Thr Gly Leu Glu same time Thr Thr Leu Ser same time Asp Glu Glu 180 185 190 same time Ala Leu same time wall Phe same time same time Ser Gly Gly Gly Gly Gly same time Thr 195 200 205 for Cys Gly Leu Thr Trp gin His Phe Lys Leu dy Asp Leu Phe Glu 210 215 220 Ile Glu Lys Thr Leu Ser Phe same time Lys Asp Ala Leu Thr gin Gly gin 225 230 235 240 Asp Tyr Asp Tyr Ile Thr Arg Thr Ser gin same time gin Gly wall Leu gin 245 250 255 Thr Thr Gly Phe wall same time Ala Glu same time Leu same time for for Phe Thr Trp 260 265 270 Ser Leu Gly Leu Leu gin Met Asp Phe Phe Tyr Arg Lys Lys Ser Trp 275 280 285 Tyr Ala Gly gin Phe Met Arg Lys Ile Thr for Lys Thr Glu Ile Lys 290 295 300 same time Lys Ile same time Ser Arg Ile Ala His Tyr Phe Thr Thr Leu Leu same time 305 310 315 320 Ala Leu Lys Arg for Leu Leu Ser wall Leu wall Arg Asp Ile Asp Lys 325 330 335 Thr Phe Arg Glu gin Lys Ile gin Leu for Leu Lys for Thr Ala Lys 340 345 350 Thr gin Ser Leu Asp Gly Ile Asp Phe Asp Phe Met His Thr Leu Ile

336

355 360 365 same time Ala Leu Met Lys gin Thr Ile gin Gly wall wall gin Tyr Cys Asp 370 375 380 Ala Lys Ile gin Ala Thr Lys Glu wall Ile Ser gin Glu Thr for Ile 385 390 395 400 gin Lys Asp Ser Leu Phe

405 (2) INFORMATION FOR SEQUENCE NO. 185:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 275 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULA TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (Ix) SIGN: (A) NAME / KEY: different characters (B) PLACEMENT 1 ... 275 (Xi) DESCRIPTION i SEQUENCES: Sequence £. 185:

Met Ser Lys Ser Leu Tyr gin Thr Leu same time wall Ser Glu same time Ala Ser 1 5 10 15 gin Asp Glu Ile Lys Lys Ser Tyr Arg Arg Leu Ala Arg gin Tyr His 20 25 30 for Asp Leu same time Lys Thr Lys Glu Ala Glu Glu Lys Phe Lys Glu Ile 35 40 45 same time Ala Ala Tyr Glu Ile Leu Ser Asp Glu Glu Lys Arg Arg gin Tyr 50 55 60 Asp gin Phe Gly Asp same time Met Phe Gly Gly gin same time Phe Ser Asp Phe 65 70 75 80 Ala Arg Ser Arg Gly for Ser Glu Asp Leu Asp Asp Ile Leu Ser Ser 85 90 95 Ile Phe Gly Lys Gly Gly Phe Ser gin Arg Phe Ser gin same time Ser gin 100 105 110 Gly Phe Ser Gly Phe same time Phe Ser same time Phe Ala for Glu same time Leu Asp 115 120 125

337

Val Thr Ile Leu Asn Val Ser Leu Asp Thr Leu Leu Gly Asn 130 135 140 Lys Lys gin wall Ser wall same time same time Glu Thr Phe Ser Leu Lys Ile for 145 150 155 160 Ile Gly wall Glu Glu Gly Glu Lys Ile Arg wall Arg same time Lys Gly Lys 165 170 175 Met Gly Arg Thr Gly Arg Gly Asp Leu Leu Leu gin Ile His Ile Glu 180 185 190 Glu Asp Glu Met Tyr Arg Arg Glu Lys Asp Asp Ile Ile gin Ile Phe 195 200 205 Asp Leu for Leu Lys Thr Ala Leu Phe Gly Gly Lys Ile Glu Ile Ala 210 215 220 Thr Trp His Lys Thr Leu Thr Leu Thr Ile for for same time Thr Lys Ala 225 230 235 240 Met gin Lys Phe Arg Ile Lys Asp Lys Gly Ile Lys Ser Arg Lys Thr 245 250 255 Ser His wall Gly Asp Cys Ile Ala Ser Ser Phe Asp Leu Leu Lys Leu 260 265 270 Lys Arg Phe 275

(2) INFORMATION FOR SEQUENCE no. 186:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 278 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULA TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix) SIGN (A) NAME / KEY: different characters (B) PLACEMENT 1 ... 278

(xi) SEQUENCE DESCRIPTION: SEQ ID NO. 186:

Met Ser Lys Ser Leu Asr Val Ser Glu Asn Ala Ser 15 10 15

Gin Asp Glu White Lys Lys Ser Tyr Arg Arg Leu Ala Arg Gin Tyr His

338

For Asp Leu Asn Lys Thr Lys Glu 40 35 same time Ala Ala Tyr Glu Ile Leu Ser 50 55 Asp gin Phe Gly Asp same time Met Phe 65 70 Ala Arg Ser Arg Gly for Ser Glu 85 Ile Phe Gly Lys Gly Gly Phe Ser 100 Gly Phe Ser Gly Phe same time Phe Ser 115 120 wall Thr Ala Ile Leu same time wall Ser 130 135 Lys Lys gin wall Ser wall same time same time 145 150 Ile Gly wall Glu Glu Gly Glu Lys 165 Met Gly Arg Thr Gly Arg Gly Asp 180 Glu Asp Glu Met Tyr Arg Arg Glu 195 200 Asp Leu for Leu Lys Thr Ala Leu 210 215 Thr Trp His Lys Thr Leu Thr Leu 225 230 Met gin Lys Phe Arg Ile Lys Asp 245 Ser His wall Gly Asp Cys Ile Ala 260 Glu Thr Leu Leu Met Ser

25 Ala Glu Glu Lys Phe 30 Lys Glu Ile Asp Glu Glu Lys 45 Arg Arg gin Tyr Gly Gly gin 60 same time Phe Ser Asp Phe Asp Leu 75 Asp Asp Ile Leu Ser 80 Ser gin 90 Arg Phe Ser gin same time 95 Ser gin 105 same time Phe Ala for Glu 110 same time Leu Asp wall Leu Asp Thr 125 Leu Leu Gly same time Glu Thr Phe 140 Ser Leu Lys Ile for Ile Arg 155 wall Arg same time Lys Gly 160 Lys Leu 170 Leu Leu gin Ile His 175 Ile Glu

185 190

Lys Asp Asp White Gin White Phe

205

Phe Gly Gly Lys White Glu White Ala 220

Thr White Pro Pro Asn Thr Lys Ala 235 240

Lys Gly White Lys Ser Arg Lys Thr 250 255

Ser Ser Phe Asp Leu For Lys White

265 270

275 (2) INFORMATION FOR SEQUENCE NO.

187:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 232 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULA TYPE: protein (iii, HYPOTHETICAL: YES

339

(vi) ORIGINAL SOURCE: Helicobacter pylori (A) ORGANISM: (Ix) SIGN: (A) TITLE / KEY: (B) LOCATION different characters 1 ... 232 (Xi) SEQUENCE DESCRIPTION: Sequence # 187:

wall wall gin Lys Phe same time Phe Tyr Lys Thr Gly Gly Met Arg Leu 1 5 10 15 His Phe Lys Thr Phe Leu Phe Ile Thr Met Ala wall Ile wall Ile 20 25 30 Thr Gly Cys Ala same time Lys Lys Lys Lys Lys Asp Glu Tyr same time Lys 35 40 45 Ala Ile Phe Trp Tyr gin Gly Ile Leu Arg Glu Ile Leu Phe Ala 50 55 60 Leu Glu Thr Ala Asp same time Tyr Tyr Ser Ser Leu gin Ser Glu His 65 70 75 same time Ser for Leu wall for Glu Ala Met Leu Ala Leu Gly gin Ala 85 90 95 Met Lys Lys Lys Glu Tyr wall Leu Ala Ser Phe Tyr Phe Asp Glu 100 105 110 Ile Lys Arg Phe Gly Thr Lys Asp same time wall Asp Tyr Leu Thr Phe 115 120 125 Lys Leu gin Ser His Tyr Tyr Ala Phe Lys same time His Ser Lys Asp 130 135 140 Glu Phe Ile Ser same time Ser Ile wall Ser Leu Gly Glu Phe Ile Glu 145 150 155 Tyr for same time Ser Arg Tyr Arg for Tyr wall Glu Tyr Met gin Ile 165 170 175 Phe Ile Leu Gly gin same time Glu Leu same time Arg Ala Ile Ala same time wall 180 185 190 Lys Lys Arg His Lys for Glu Gly wall Lys Arg Tyr Leu Glu Arg 195 200 205 Asp Glu Thr Leu Glu Lys Glu Thr Lys for Lys for Ser His Met 210 215 220 Trp Tyr wall Leu Ile Phe Asp Trp

Lys

Gly

for

Asn ile

His

Tyr

Leu

gin

Lys

160

Lys

Tyr ile

for

225 230 (2) INFORMATION FOR SEQUENCE NO. 188:

(i) SEQUENCE CHARACTERISTICS:

340 (A) LENGTH: 114 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULA TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) NAME / KEY: various characters (B) LOCATION 1 ... 114 (xi) SEQUENCE DESCRIPTION: Sequence £. 188:

Met Arg Phe Leu same time same time Lys His Arg Glu Lys Gly Leu Lys Ala Glu 1 5 10 15 Glu Glu Ala Cys Gly Phe Leu Lys Thr Leu Gly Phe Glu Met Ile Glu 20 25 30 Arg same time Phe Phe Ser gin Phe Gly Glu Ile Asp Ile Ile Ala Leu Lys 35 40 45 Lys Gly wall Leu His Phe Ile Glu wall Lys Ser Gly Glu same time Phe Asp 50 55 60 for Ile Tyr Ala Ile Thr for Ser Lys Leu Lys Lys Met Ile Lys Thr 65 70 75 80 Ile Arg Cys Tyr Leu Ser gin Lys Asp for same time Ser Asp Phe Cys Ile 85 90 95 Asp Ala Leu Ile wall Lys same time Gly Lys Phe Glu Leu Leu Glu same time Ile 100 105 110 Thr Phe

(2) INFORMATION FOR SEQUENCE NO. 189:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 101 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULA TYPE: protein (iii) HYPOTHETICAL: YES

341 (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix) SIGN (A) NAME / KEY: different characters (B) PLACEMENT 1 ... 101

(xi) SEQUENCE DESCRIPTION: SEQ ID NO. 189:

Met Gly Ser Ile Gly Ala Met Thr Lys Gly Ser Ser Asp Arg Tyr Phe 1 5 10 15 gin Glu Gly wall Ala Ser Glu Lys Leu wall for Glu Gly Ile Glu Gly 20 25 30 Arg wall for Tyr Arg Gly Lys wall Ser Asp Met Ile Phe gin Leu wall 35 40 45 Gly Gly wall Arg Ser Ser Met Gly Tyr gin Gly Ala Lys same time Ile Leu 50 55 60 Glu Leu Tyr gin same time Ala Glu Phe wall Glu Ile Thr Ser Ala Gly Leu 65 70 75 80 Lys Lys Ser His wall His Gly wall Asp Ile Thr Lys Glu Ala for same time 85 90 95 Ile Met Gly Glu Phe 100

(2) INFORMATION FOR SEQUENCE NO. 190:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 481 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULA TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix) SIGN: (A) NAME / KEY: different characters (B) PLACEMENT 1 ... 482

(xi) SEQUENCE DESCRIPTION: SEQ ID NO. 190:

342

Met Arg Ile Leu gin Arg Ala Leu Thr Phe Glu Asp wall Leu Met wall 1 5 10 15 for Arg Lys Ser Ser wall Leu for Lys Asp wall Ser Leu Lys Ser Arg 20 25 30 Leu Thr Lys same time Ile Gly Leu same time Ile for Phe Ile Ser Ala Ala Met 35 40 45 Asp Thr wall Thr Glu His Lys Thr Ala Ile Ala Met Ala Arg Leu Gly 50 55 60 Gly Ile Gly Ile wall His Lys same time Met Asp Ile gin Thr gin wall Lys 65 70 75 80 Glu Ile Thr Lys wall Lys Lys Ser Glu Ser Gly wall Ile same time Asp for 85 90 95 Ile Phe Ile His Ala His Arg Thr Leu Ala Asp Ala Lys wall Ile Thr 100 105 110 Asp same time Tyr Lys Ile Ser Gly wall for wall wall Asp Asp Lys Gly Leu 115 120 125 Leu Ile Gly Ile Leu Thr same time Arg Asp wall Arg Phe Glu Thr Asp Leu 130 135 140 Ser Lys Lys wall Gly Asp wall Met Thr Lys Met for Leu wall Thr Ala 145 150 155 160 His wall Gly Ile Ser Leu Asp Glu Ala Ser Asp Leu Met His Lys His 165 170 175 Lys Ile Glu Lys Leu for Ile wall Asp Lys Asp same time wall Leu Lys Gly 180 185 190 Leu Ile Thr Ile Lys Asp Ile gin Lys Arg Ile Glu Tyr for Glu Ala 195 200 205 same time Lys Asp Asp Phe Gly Arg Leu Arg wall Gly Ala Ala Ile Gly wall 210 215 220 Gly gin Leu Asp Arg Ala Glu Met Leu wall Lys Ala Gly wall Asp Ala 225 230 235 240 Leu wall Leu Asp Ser Ala His Gly His Ser Ala same time Ile Leu His Thr 245 250 255 Leu Glu Glu Ile Lys Lys Ser Leu wall wall Asp wall Ile wall Gly same time 260 265 270 wall wall Thr Lys Glu Ala Thr Ser Asp Leu Ile Ser Ala Gly Ala Asp 275 280 285 Ala wall Lys wall Gly Ile Gly for Gly Ser Ile Cys Thr Thr Arg Ile 290 295 300 wall Ala Gly wall Gly Met for gin wall Ser Ala Ile Asp same time Cys wall 305 310 315 320 Glu wall Ala Ser Lys Phe Asp Ile for wall Ile Ala Asp Gly Gly Ile 325 330 335 Arg Tyr Ser Gly Asp wall Ala Lys Ala Leu Ala Leu Gly Ala Ser Ser

343

340 345 350 wall Met Ile Gly Ser Leu Leu Ala Gly Thr Glu Glu Ser for Gly Asp 355 360 365 Phe Met Ile Tyr gin Gly Arg gin Tyr Lys Ser Tyr Arg Gly Met Gly 370 375 380 Ser Ile Gly Ala Met Thr Lys Gly Ser Ser Asp Arg Tyr Phe gin Glu 385 390 395 400 Gly wall Ala Ser Glu Lys Leu wall for Glu Gly Ile Glu Gly Arg wall 405 410 415 for Tyr Arg Gly Lys wall Ser Asp Met Ile Phe gin Leu wall Gly Gly 420 425 430 wall Arg Ser Ser Met Gly Tyr gin Gly Ala Lys same time Ile Leu Glu Leu 435 440 445 Tyr gin same time Ala Glu Phe wall Glu Ile Thr Ser Ala Gly Leu Lys Glu 450 455 4 60 Ser His wall His Gly wall Asp Ile Thr Lys Glu Ala for same time Tyr Tyr 465 470 475 480

Gly (2) SEQ ID NO. 191:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 204 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULA TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) NAME / KEY: various characters (B) LOCATION 1 ... 204 (xi) SEQUENCE DESCRIPTION: Sequence no. 191:

Met gin Gly Phe Leu Leu gin Thr gin Ser Ile Arg Asp Glu Asp Leu 1 5 10 15 Ile wall His wall Leu Thr Lys same time gin Leu Lys Thr Leu Tyr Arg Phe 20 25 30

344

Tyr Gly Lys Arg His Ser Val Leu Asn Val Gly Arg Lys White Asp Phe 35 40 45

Glu Glu Glu Asn Asp Asp Lys Phe Leu For Lys Leu Arg Asn Leu

55 60

His Leu Gly Tyr White Trp Glu Arg Glu Met Glu Arg Leu Phe Phe Trp

70

Gin Arg Phe Cys Ala Leu Phu Lys His Leu Glu Gly Val His Ser

90 95

Leu Asp Ser Il Tyr Phe Asp Thr Leu Asp Asp Gly Ala Ser Lys Leu

100 105 110

Ser Lys Gin His For Leu Arg Val White Leu Glu Met Tyr Ala Val Leu

115 120 125

Leu Asn Phe Glu Gly Arg Leu Gin Ser Tyr Asn Ser Cys Phe Leu Cys

129 135 140

Asp Ala Lys Le Glu Arg Ser Val Ala Leu Ala Gin Gly Phe Leu

145 150 155 160

Ala His Pro Ser Cys Leu Lys

165 170 175

Gin Ala Phe Phe Arg Thr Gin Ser Thr ile Asp Leu Glu Thr Glu Glu

180 185 190

Val Glu, Glu Leu Trp Arg Thr Leu Asn Leu Gly Phe

195 200 (2) INFORMATION FOR SEQUENCE NO. 192:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 82 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULA TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix) SIGN: (A) NAME / KEY: different characters (B) PLACEMENT 1 ... 82

(xi) SEQUENCE DESCRIPTION: SEQ ID NO. 192:

Met Gly Val Gly Arg Val Gly Asn

345

10 15

for Met Gly Ile Gly Ala Ile Ala Ile Ala Ile same time Gly Gly Arg gin 20 25 30 Arg Ser Arg Met Leu wall wall Asp Ile Asp Asp Lys Arg Leu Glu gin 35 40 45 wall gin Lys Met Leu for Gly same time Trp Arg for wall Thr Ala Leu Ser 50 55 60 Trp Cys Leu Cys Ile for Lys Arg Gly Ala Ile Arg Ala Arg Cys Cys 65 70 75 80 Glu Arg

(2) INFORMATION FOR SEQUENCE NO. 193:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 67 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULA TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (Ix) SIGN: (A) NAME / KEY: different characters (B, PLACEMENT 1 ... 67 (Xi) DESCRIPTION i SEQUENCES: Sequence # 193:

Le Ser Gly Thr Ala Val Ser Cys Arg Cys Thr Cys Arg

Val Leu Val Arg Thr Serie Pro Val Valie Gly Cys Ser Cys Pro

25 30

Phe Leu Ser Ser Gly Phe Thr Thr Gly Thr His Gin Ser Pro Val

40 45

Lys Lys Cys Gly Val Asn Ala Lys Lys Thr Pro Ser Lys Lys His Leu

50 55 60 HLS Leu Asn 65

(2) INFORMATION FOR SEQUENCE NO. 194

346 (i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 114 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULA TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) TITLE / KEY: various characters (B) LOCATION 1 ... 114 (xi) SEQUENCE DESCRIPTION: Sequence no. 194:

Val Trp Leu Ala Ala Leu Gly Phe Leu Clay Thr Ala Val Gly Leu Pro 15 10 15

Val Lila Thr Val Lila Ala Leu Ala Lys Val Gly Ser Ser Ser Thr Pro

25 30

Ser Ala Gly Met Pro Ala Ala Cys Trp Arg Arg Ser

40 45

Ala Thr Trp Arg

55 60

Cys Pro Ser Lys Ser Ser Val Val Leu Leu Gly Glu Glu Ala Ala

70

Arg Arg Cys Ser Ser Thr Ala Trp

90 95

Ser Ala Ser Ser Ala Ser Ser

100 105 110

Pro Arg (2) INFORMATION FOR SEQUENCE NO. 195:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 20 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular

347 (ii) MOLECULA TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) NAME / KEY: various characters (B) LOCATION 1 ... 20 (xi) SEQUENCE DESCRIPTION: Sequence no. 195:

TATACCATGG TGGGCGCTAA 20 (2) INFORMATION FOR SEQUENCE NO. 196:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 23 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular (ii) MOLECULA TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE : NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) TITLE / KEY: various characters (B) LOCATION 1 ... 23 (xi) SEQUENCE DESCRIPTION: Sequence no. 196:

ATGAATTCGA GTAAGGATTT TTG 23 (2) INFORMATION FOR SEQUENCE NO. 197:

348 (i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 22 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular (ii) MOLECULAR TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE : NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) NAME / KEY: various characters (B) LOCATION 1 ... 22 (xi) SEQUENCE DESCRIPTION: Sequence no. 197:

TTAACCATGG TGAAAAGCGA TA 22 (2) INFORMATION FOR SEQUENCE NO. 198:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 23 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular (ii) MOLECULA TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE : NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) TITLE / KEY: various characters (B) LOCATION 1 ... 23

349 (xi) SEQUENCE DESCRIPTION: SEQ ID NO. 198:

TAGAATTCGC ATAACGATCA ATC 23 (2) INFORMATION FOR SEQUENCE NO. 199:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 22 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular (ii) MOLECULAR TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE : NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) NAME / KEY: various characters (B) LOCATION 1 ... 22 (xi) SEQUENCE DESCRIPTION: Sequence no. 199:

ATATCCATGG TGAGTTTGAT GA 22 (2) INFORMATION FOR SEQUENCE NO. 200:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 25 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular (ii) MOLECULAR TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE : NO (vi, ORIGINAL SOURCE:

350 (A) ORGANISM: Helicobacter pylori (ix)

(A) NAME / KEY: various characters (B) LOCATION 1 ... 25 (xi) SEQUENCE DESCRIPTION: Sequence no. 200:

ATGAATTCAA TTTTTTATTT TGCCA 25 (2) INFORMATION FOR SEQUENCE NO. 201:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 21 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular (ii) MOLECULAR TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE : NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) TITLE / KEY: various characters (B) LOCATION 1 ... 21 (xi) SEQUENCE DESCRIPTION: Seq. 201:

AATTCCATGG TGGGGGCTAT G 21 (2) INFORMATION FOR SEQUENCE NO. 202:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 23 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular (ii) MOLECULA TYPE: DNA (genomic)

351 (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) NAME / KEY: various characters (B) LOCATION 1 ... 23 (xi) SEQUENCE DESCRIPTION: Sequence £. 202:

ATGAATTCTC GATAGCCAAA ATC 23 (2) INFORMATION FOR SEQUENCE NO. 203:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 25 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular (ii) MOLECULAR TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE : NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) NAME / KEY: different characters (B) LOCATION 1 ... 25 (xi) SEQUENCE DESCRIPTION: Sequence £. 203:

AATTCCATGG TGCATAACTT CCATT 25 (2) INFORMATION FOR SEQUENCE NO. 204:

(i) SEQUENCE CHARACTERISTICS:

352 (A) LENGTH: 25 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular (ii) MOLECULA TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI- SENSE: NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) NAME / KEY: various characters (B) LOCATION 1 ... 25 (xi) SEQUENCE DESCRIPTION: Sequence no. 204:

AAGAATTCTC TAGCATCCAA ATGGA 25 (2) INFORMATION FOR SEQUENCE NO. 205:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 24 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D, TOPOLOGY: circular (ii) MOLECULA TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE : NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) NAME / KEY: various characters (B) LOCATION 1 ... 24 (xi) SEQUENCE DESCRIPTION: Sequence no. 205:

353

ATTTCCATGG TCATGTCTCA TATT 24 (2) INFORMATION FOR SEQUENCE NO. 206:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 23 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular (ii) MOLECULA TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE : NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) TITLE / KEY: various characters (B) LOCATION 1 ... 23 (xi) SEQUENCE DESCRIPTION: Sequence no. 206:

ATGAATTCCA TCTTTTATTC CAC 23 (2) INFORMATION FOR SEQUENCE NO. 207:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 27 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular (ii) MOLECULAR TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE : NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori

354 (ix) SIGN:

(A) NAME / KEY: various characters (B) LOCATION 1 ... 27 (xi) SEQUENCE DESCRIPTION: Sequence £. 207:

AACCATGGTG ATTTTAAGCA TTGAAAG 27 (2) INFORMATION FOR SEQUENCE NO. 208:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 28 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular (ii) MOLECULA TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE : NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) NAME / KEY: various characters (B) LOCATION 1 ... 28 (xi) SEQUENCE DESCRIPTION: Sequence no. 208:

AAGAATTCCA CTCAAAATTT TTTAACAG 28 (2) INFORMATION FOR SEQUENCE NO. 209:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 25 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular (ii) MOLECULA TYPE: DNA (genomic)

355

(Iii) HYPOTHETICAL: NO (Iv) ANTI-SENSE: NO (Vi) ORIGINAL SOURCE: (A) ORGANISM: Helicobacter pylori (Ix) SIGN: (A) TITLE / KEY: (B) LOCATION different characters 1 ... 25 (Xi) SEQUENCE DESCRIPTION: Sequence £. 209:

GATCATCCAT ATGTTATCTT CTAAT 25 (2) INFORMATION FOR SEQUENCE NO. 210:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 23 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular (ii) MOLECULA TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE : NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) NAME / KEY: different characters (B) LOCATION 1 ... 23 (xi) SEQUENCE DESCRIPTION: Sequence ô. 210:

TGAATTCAAC CATTTTAACC CTG 23 (2) SEQ ID NO. 211:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 27 base pairs

356 (B) TYPE: nucleic acid (C) NUMBER OF FIBERS: two (D) TOPOLOGY: circular (ii) MOLECULAR TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE :

(A) ORGANISM: Helicobacter pylori (ix)

(A) NAME / KEY: different characters (B) LOCATION 1 ... 27 (xi) SEQUENCE DESCRIPTION: Sequence ô. 211:

TATACCATGG TGAAATTTTT TCTTTTA 27 (2) INFORMATION FOR SEQUENCE NO. 212:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 25 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular (ii) MOLECULAR TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE : NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) NAME / KEY: various characters (B) LOCATION 1 ... 25 (xi) SEQUENCE DESCRIPTION: Sequence no. 212:

357

AGAATTCAAT TGCGTCTTGT AAAAG 25 (2) INFORMATION FOR SEQUENCE NO. 213:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 24 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular (ii) MOLECULAR TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE : NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) NAME / KEY: various characters (B) LOCATION 1 ... 24 (xi) SEQUENCE DESCRIPTION: Sequence no. 213:

TATACCATGG TGATGGACAA ACTC 24 (2) INFORMATION FOR SEQUENCE NO. 214:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 23 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular (ii) MOLECULA TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE : NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori

358 (ix) SIGN:

(A) TITLE / KEY: various characters (B) LOCATION 1 ... 23 (xi) SEQUENCE DESCRIPTION: Sequence no. 214:

ATGAATTCCC ACTTGGGGCG ATA 23 (2, INFORMATION FOR SEQUENCE # 215:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 25 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular (ii) MOLECULAR TYPE: DNA (genomic) (iii, HYPOTHETICAL: NO (iv) ANTI-SENSE : NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) NAME / KEY: different characters (B) LOCATION 1 ... 25 (xi) SEQUENCE DESCRIPTION: Sequence £. 215:

TTATGGATCC AAACCAATTA AAACT 25 (2) SEQ ID NO. 216:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 23 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular (ii) MOLECULAR TYPE: DNA (genomic) (iii) HYPOTHETHIC: NO

359

(iv) ANTI-SENSE: NO (Vi) ORIGINAL SOURCE: (A) ORGANISM: Helicobacter pylori (Ix) SIGN: (A) TITLE / KEY: (B) LOCATION different characters 1 ... 23 (Xi) SEQUENCE DESCRIPTION: Sequence £. 216:

TATCTCGAGT TATAGAGAAG GGC 23 (2) INFORMATION FOR SEQUENCE NO. 217:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 22 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular (ii) MOLECULAR TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE : NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) NAME / KEY: various characters (B) LOCATION 1 ... 22 (xi) SEQUENCE DESCRIPTION: Sequence no. 217:

TTAACCATGG TGAAAAGCGA TA 22 (2) INFORMATION FOR SEQUENCE NO. 218:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 24 base pairs (B) TYPE: nucleic acid

360 (C) NUMBER OF FIBERS: two (D) TOPOLOGY: circular (ii) MOLECULAR TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) NAME / KEY: various characters (B) LOCATION 1 ... 24 (xi) SEQUENCE DESCRIPTION: Sequence £. 218:

TAGAATTCGC CTCTAAAACT TTAG 24 (2) INFORMATION FOR SEQUENCE NO. 219:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 22 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular (ii) MOLECULAR TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE : NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) NAME / KEY: various characters (B) LOCATION 1 ... 22 (xi) SEQUENCE DESCRIPTION: Sequence no. 219:

TTAACCATGG TGAAAAGCGA TA

361 (2) INFORMATION FOR SEQUENCE NO. 220:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 23 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular (ii) MOLECULAR TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE : NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) TITLE / KEY: various characters (B) LOCATION 1 ... 23 (xi) SEQUENCE DESCRIPTION: Sequence no. 220:

TAGAATTCGC ATAACGATCA ATC 23 (2) INFORMATION FOR SEQUENCE NO. 221:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 22 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular (ii) MOLECULAR TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE : NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

362 (A) NAME / KEY: miscellaneous characters (B) LOCATION 1 ... 22 (xi) SEQUENCE DESCRIPTION: Sequence no. 221:

ATATCCATGG TGAGTTTGAT GA 22 (2) INFORMATION FOR SEQUENCE NO. 222:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 25 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular (ii) MOLECULAR TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE : NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) NAME / KEY: various characters (B) LOCATION 1 ... 25 (xi) SEQUENCE DESCRIPTION: Sequence no. 222:

ATGAATTCAA TTTTTTATTT TGCCA 25 (2) INFORMATION FOR SEQUENCE NO. 223:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 23 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular (ii) MOLECULAR TYPE: DNA (genomic) (iii) HYPOTHETHIC: NO

363

(Iv) ANTI-SENSE: NO (Vi) ORIGINAL SOURCE: (A) ORGANISM: Helicobacter pylori (Ix) SIGN: (A) TITLE / KEY: (B) LOCATION different characters 1 ... 23 (Xi) SEQUENCE DESCRIPTION: Sequence # 223:

AATTCCATGG CTATCCAAAT CCG 23 (2) INFORMATION FOR SEQUENCE NO. 224:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 25 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular (ii) MOLECULAR TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE : NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) NAME / KEY: different characters (B) LOCATION 1 ... 25 (xi) SEQUENCE DESCRIPTION: Sequence £. 224:

ATGAATTCGC CAAAATCGTA GTATT 25 (2) INFORMATION FOR SEQUENCE NO. 225:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 24 base pairs (B) TYPE: nucleic acid (C) FIBERS: two

364 (D) TOPOLOGY: circular (ii) MOLECULA TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) NAME / KEY: various characters (B) LOCATION 1 ... 24 (xi) SEQUENCE DESCRIPTION: Sequence no. 225:

GATACCATGG AATTTATGAA AAAG 24 (2) INFORMATION FOR SEQUENCE NO. 226:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 25 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular (ii) MOLECULAR TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE : NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) NAME / KEY: different characters (B) LOCATION 1 ... 25 (xi) SEQUENCE DESCRIPTION: Sequence £. 226:

TGAATTCGAA AAAGTGTAGT TATAC

365 (2) INFORMATION FOR SEQUENCE NO. 227:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 19 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular (ii) MOLECULAR TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE : NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) NAME / KEY: various characters (B) LOCATION 1 ... 19 (xi) SEQUENCE DESCRIPTION: Sequence no. 227:

CCCTTCATTT TAGAAATCG 19 (2) INFORMATION FOR SEQUENCE NO. 228:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 20 base pairs (B) TYPE: nucleic acid (C) NUMBER OF FIBERS: two (D) TOPOLOGY: circular (ii) MOLECULAR TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE : NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) TITLE / KEY: different characters

366 (B) LOCATION 1 ... 20 (xi) SEQUENCE DESCRIPTION: Seq. 228:

ATTTCAACCA ATTCAATGCG 20 (2) INFORMATION FOR SEQUENCE NO. 229:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 20 base pairs (B) TYPE: nucleic acid (C) NUMBER OF FIBERS: two (D) TOPOLOGY: circular (ii) MOLECULAR TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE : NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) NAME / KEY: various characters (B) LOCATION 1 ... 20 (xi) SEQUENCE DESCRIPTION: Sequence no. 229:

GCCCCTTTTG ATTTGAAGCT 20 (2) INFORMATION FOR SEQUENCE NO. 230:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 22 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular (ii) MOLECULAR TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE : NOT

367 (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (Ix) SIGN: (A) NAME / KEY: different characters (B) PLACEMENT 1 ... 22 (Xi) DESCRIPTION i SEQUENCES: Sequence £. 230:

TCGCTCCAAG ATACCAAGAA GT 22 (2) INFORMATION FOR SEQUENCE NO. 231:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 22 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular (ii) MOLECULAR TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE : NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) NAME / KEY: various characters (B) LOCATION 1 ... 22 (xi) SEQUENCE DESCRIPTION: Sequence no. 231:

CTTGAATTAG GGGCAAAGAT CG 22 (2) INFORMATION FOR SEQUENCE NO. 232:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 22 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular

368 (ii) MOLECULA TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) NAME / KEY: various characters (B) LOCATION 1 ... 22 (xi) SEQUENCE DESCRIPTION: Sequence no. 232:

ATGCGTTTTT ACCCAAAGAA GT 22 (2) INFORMATION FOR SEQUENCE NO. 233:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 22 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular (ii) MOLECULAR TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE : NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) NAME / KEY: different characters (B) LOCATION 1 ... 22 (xi) SEQUENCE DESCRIPTION: Sequence ô. 233:

ATAACGCCAC TTCCTTATTG GT 22 (2) INFORMATION FOR SEQUENCE NO. 234:

369 (i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 19 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular (ii) MOLECULAR TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE : NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) NAME / KEY: various characters (B) LOCATION 1 ... 19 (xi) SEQUENCE DESCRIPTION: Sequence no. 234:

CTTTGGGTAA AAACGCATC 19 (2) INFORMATION FOR SEQUENCE NO. 235:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 20 base pairs (B) TYPE: nucleic acid (C) NUMBER OF FIBERS: two (D) TOPOLOGY: circular (ii) MOLECULAR TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE : NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) TITLE / KEY: various characters (B) LOCATION 1 ... 20

370 (xi) SEQUENCE DESCRIPTION: SEQ ID NO. 235:

CGATCTTTGA TCCTAATTCA (2) INFORMATION FOR SEQUENCE NO. 236:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 19 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular

(ii) MOLECULA TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix) SIGN: (A) NAME / KEY: different characters (B) PLACEMENT 1 ... 19

(xi) SEQUENCE DESCRIPTION: Sequence £. 236:

ATCAAGTTGC CTATGCTGA (2) INFORMATION FOR SEQUENCE NO. 237:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 22 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular (ii) MOLECULAR TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE : NOT

371 (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (Ix) SIGN: (A) NAME / KEY: different characters (B) PLACEMENT 1 ... 22 (Xi) DESCRIPTION > SEQUENCES: Sequence # 237:

TTGAACACTT TTGATTATGC GG 22 (2) SEQ ID NO. 238:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 23 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular (ii) MOLECULA TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE : NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) NAME / KEY: various characters (B) LOCATION 1 ... 23 (xi) SEQUENCE DESCRIPTION: Sequence £. 238:

GGATTATGCG ATTGTTTTAC AAG 23 (2) INFORMATION FOR SEQUENCE NO. 239:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 21 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular

372 (ii) MOLECULA TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) NAME / KEY: different characters (B) LOCATION 1 ... 21 (xi) SEQUENCE DESCRIPTION: Sequence £. 239:

GTCTTTAGCA AAAATGGCGT C 21 (2) INFORMATION FOR SEQUENCE NO. 240:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 21 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular (ii) MOLECULAR TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE : NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) NAME / KEY: different characters (B) LOCATION 1 ... 21 (xi) SEQUENCE DESCRIPTION: Sequence £. 240:

AATGAGCGTA AGAGAGCCTT C 21 (2) INFORMATION FOR SEQUENCE NO. 241:

373 (i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 18 base pairs (B) TYPE: nucleic acid (C) NUMBER OF FIBERS: two (D) TOPOLOGY: circular (ii) MOLECULA TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE : NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) NAME / KEY: various characters (B) LOCATION 1 ... 18 (xi) SEQUENCE DESCRIPTION: Sequence £. 241:

CTTATGGGGG TATTGTCA 18 (2) INFORMATION FOR SEQUENCE NO. 242:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 18 base pairs (B) TYPE: nucleic acid (C) NUMBER OF FIBERS: two (D) TOPOLOGY: circular (ii) MOLECULA TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE : NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) TITLE / KEY: different characters (B) LOCATION 1 ... 18

374 (xi) SEQUENCE DESCRIPTION: SEQ ID NO. 242:

AGCATGTGGG TATCCAGC 18 (2) INFORMATION FOR SEQUENCE NO. 243:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 19 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular (ii) MOLECULAR TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE : NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) NAME / KEY: different characters (B) LOCATION 1 ... 19 (xi) SEQUENCE DESCRIPTION: Sequence £. 243:

AGGTTGTTGC CTAAAGACT 19 (2) INFORMATION FOR SEQUENCE NO. 244:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 18 base pairs (B) TYPE: nucleic acid (C) NUMBER OF FIBERS: two (D) TOPOLOGY: circular (ii) MOLECULA TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE : NO (vi) ORIGINAL SOURCE:

375 (A) ORGANISM: Helicobacter pylori (ix)

(A) NAME / KEY: various characters (B) LOCATION 1 ... 18 (xi) SEQUENCE DESCRIPTION: Sequence no. 244:

CTGCCTCCAC CTTTGATC 18 (2) SEQ ID NO. 245:

(i, SEQUENCE CHARACTERISTICS:

(A) LENGTH: 19 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular (ii) MOLECULAR TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE : NO (vi, ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) NAME / KEY: various characters (B) LOCATION 1 ... 19 (xi) SEQUENCE DESCRIPTION: Sequence no. 245:

ACCAATATCA ATTGGCACT 19 (2) INFORMATION FOR SEQUENCE NO. 246:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 18 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular (ii) MOLECULA TYPE: DNA (genomic)

376

(Iii) HYPOTHETICAL: NO (Iv) ANTI-SENSE: NO (Vi) ORIGINAL SOURCE: (A) ORGANISM: Helicobacter pylori (Ix) SIGN: (A) TITLE / KEY: (B) LOCATION different characters 1 ... 18 (Xi) SEQUENCE DESCRIPTION: Sequence £. 246:

ACTTGGAAAA GCTCTGCA 18 (2) INFORMATION FOR SEQUENCE NO. 247:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 19 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular (ii) MOLECULAR TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE : NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) NAME / KEY: various characters (B) LOCATION 1 ... 19 (xi) SEQUENCE DESCRIPTION: Sequence no. 247:

CTTGCTTGTC ATATCTAGC 19 (2) INFORMATION FOR SEQUENCE NO. 248:

(i) SEQUENCE CHARACTERISTICS:

377 (A) LENGTH: 18 base pairs (B) TYPE: nucleic acid (C) NUMBER OF FIBERS: two (D) TOPOLOGY: circular (ii) MOLECULA TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI- SENSE: NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) NAME / KEY: various characters (B) LOCATION 1 ... 18 (xi) SEQUENCE DESCRIPTION: Sequence no. 248:

GTTGAAGTGT TGGTGCTA 18 (2) INFORMATION FOR SEQUENCE NO. 249:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 22 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular (ii) MOLECULAR TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE : NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) NAME / KEY: various characters (B) LOCATION 1 ... 22 (xi) SEQUENCE DESCRIPTION: Sequence no. 249:

378

CAAGCAAGTG GTTTGGTTTT AG 22 (2) INFORMATION FOR SEQUENCE NO. 250:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 22 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular (ii) MOLECULAR TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE : NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) NAME / KEY: various characters (B) LOCATION 1 ... 22 (xi) SEQUENCE DESCRIPTION: Sequence no. 250:

TGGAAAGAGC AAATCATTGA AG 22 (2) INFORMATION FOR SEQUENCE NO. 251:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 21 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular (ii) MOLECULAR TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE : NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori

379 (ix) SIGN:

(A) TITLE / KEY: various characters (B) LOCATION 1 ... 21 (xi) SEQUENCE DESCRIPTION: Seq. 251:

GCCCATAATC AAAAAGCCCA T 21 (2) INFORMATION FOR SEQUENCE NO. 252:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 24 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular (ii) MOLECULAR TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE : NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) NAME / KEY: various characters (B) LOCATION 1 ... 24 (xi) SEQUENCE DESCRIPTION: Sequence no. 252:

CTAAAACCAA ACCACTTGCT TGTC 24 (2) SEQ ID NO. 253:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 16 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular (ii) MOLECULA TYPE: DNA (genomic)

380

(iii) HYPOTHETICAL: NO (Iv) ANTI-SENSE: NO (Vi) ORIGINAL SOURCE: (A) ORGANISM: Helicobacter pylori (Ix) SIGN: (A) TITLE / KEY: (B) LOCATION different characters 1 ... 16 (Xi) SEQUENCE DESCRIPTION: Sequence £. 253:

GTAAAACGAC GGCCAG 16 (2) INFORMATION FOR SEQUENCE NO. 254:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 17 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular (ii) MOLECULAR TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE : NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) NAME / KEY: various characters (B) LOCATION 1 ... 17 (xi) SEQUENCE DESCRIPTION: Sequence no. 254:

CAGGAAACAG CTATGAC 17 (2) INFORMATION FOR SEQUENCE NO. 255:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 21 base pairs

381 (B) TYPE: nucleic acid (C) NUMBER OF FIBERS: two (D) TOPOLOGY: circular (ii) MOLECULAR TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE :

(A) ORGANISM: Helicobacter pylori (ix)

(A) TITLE / KEY: various characters (B) LOCATION 1 ... 21 (xi) SEQUENCE DESCRIPTION: Seq. 255:

ATCTTACCTA TCACCTCAAA T (2) INFORMATION FOR SEQUENCE NO. 256:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 21 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular (ii) MOLECULAR TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE : NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) NAME / KEY: different characters (B) LOCATION 1 ... 21 (xi) SEQUENCE DESCRIPTION: Sequence £. 256:

382

AGACAGCAAC ATCTTTGTGA A 21 (2) INFORMATION FOR SEQUENCE NO. 257:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 50 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular (ii) MOLECULAR TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE : NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) NAME / KEY: different characters (B) LOCATION 1 ... 50 (xi) SEQUENCE DESCRIPTION: Sequence £. 257:

CGCGGATCCA TATGGCTGAA AAAACGCCTT TTTTTAAAAC TAAAAACCAC 50 (2) INFORMATION FOR SEQUENCE NO. 258:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 34 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular (ii) MOLECULAR TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE : NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori

383 (ix) SIGN:

(A) TITLE / KEY: various characters (B) LOCATION 1 ... 34 (xi) SEQUENCE DESCRIPTION: Seq. 258:

CCGGAATTCA TCAGTATTCA ATGGGAATAA AGCC 34 (2) INFORMATION FOR SEQUENCE NO. 259:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 50 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular (ii) MOLECULAR TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE : NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) TITLE / KEY: various characters (B) LOCATION 1 ... 50 (xi) SEQUENCE DESCRIPTION: Sequence no. 259:

CGCGGATCCA TATGAAAGAA GAAGAAAAAG AAGAAAAAAA GACAGAAAGG 50 (2) 260:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 37 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular (ii) MOLECULAR TYPE: DNA (genomic) (iii) HYPOTHETHIC: NO

384

(iv) ANTI-SENSE: NO (Vi) ORIGINAL SOURCE: (A) ORGANISM: Helicobacter pylori (Ix) SIGN: (A) TITLE / KEY: (B) LOCATION different characters 1 ... 37 (Xi) SEQUENCE DESCRIPTION: Sequence £. 260:

CCGGAATTCG CTTAAAAGAA AATAGTCCCC CAAACGC 37 (2) SEQ ID NO. 261:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 43 base pairs (B) TYPE: nucleic acid (C) NUMBER OF FIBERS: two (D, TOPOLOGY: circular (ii) MOLECULAR TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE : NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) NAME / KEY: different characters (B) LOCATION 1 ... 43 (xi) SEQUENCE DESCRIPTION: Sequence £. 261:

CGCGGATCCA TATGAAAGAG GTCATTCCCA CCCCTTCAAC CCC 43 (2) SEQ ID NO. 262:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 36 base pairs (B) TYPE: nucleic acid

385 (C) NUMBER OF FIBERS: two (D) TOPOLOGY: circular (ii) MOLECULAR TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) NAME / KEY: various characters (B) LOCATION 1 ... 36 (xi) SEQUENCE DESCRIPTION: Sequence no. 262:

CCGGAATTCA TATAAATATC ATATAGGCAG AAAAAC 36 (2) INFORMATION FOR SEQUENCE NO. 263:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 37 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular (ii) MOLECULAR TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE : NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) NAME / KEY: various characters (B) LOCATION 1 ... 37 (xi) SEQUENCE DESCRIPTION: Sequence no. 263:

CGCGGATCCA TATGGAGGCA GAGCTTGATG AAAAATC

386 (2) INFORMATION FOR SEQUENCE NO. 264

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 36 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular (ii) MOLECULAR TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE : NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) NAME / KEY: various characters (B) LOCATION 1 ... 36 (xi) SEQUENCE DESCRIPTION: Sequence C. 264:

CCGGAATTCG ATTGATTTTG TCAAATCTAÄ AATCCC 36 (2) INFORMATION FOR SEQUENCE NO. 265:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 25 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular (ii) MOLECULAR TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE : NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

387 (A) TITLE / KEY: various characters (B) LOCATION 1 ... 25 (xi) SEQUENCE DESCRIPTION: Sequence no. 265:

TATTATACAT ATGGAAGAAG ATGGG 25 (2) INFORMATION FOR SEQUENCE NO. 266:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 23 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular (ii) MOLECULA TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE : NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) TITLE / KEY: various characters (B) LOCATION 1 ... 23 (xi) SEQUENCE DESCRIPTION: Sequence no. 266:

TAATCTCGAG TTTAGAAGGC GTA 23 (2) INFORMATION FOR SEQUENCE NO. 267:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 25 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular (ii) MOLECULA TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO

388

(iv) ANTI-SENSE: NO (Vi) ORIGINAL SOURCE: (A) ORGANISM: Helicobacter pylori (Ix) SIGN: (A) TITLE / KEY: (B) LOCATION different characters 1 ... 25 (Xi) SEQUENCE DESCRIPTION: Sequence £. 267:

TTATATTCAT ATGGAAGACG ATGGC 25 (2) INFORMATION FOR SEQUENCE NO. 268:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 24 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular (ii) MOLECULAR TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE : NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) NAME / KEY: various characters (B) LOCATION 1 ... 24 (xi) SEQUENCE DESCRIPTION: Sequence £. 268:

AATTCTCGAG CCTCTTTATA AGCC 24 (2) INFORMATION FOR SEQUENCE NO. 269:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 46 base pairs (B) TYPE: nucleic acid (C) FIBERS: two

389 (D) TOPOLOGY: circular (ii) MOLECULA TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) NAME / KEY: various characters (B) LOCATION 1 ... 46 (xi) SEQUENCE DESCRIPTION: Sequence no. 269:

CGCGGATCCA TATGGTAGAA GCCTTTCAAA AACACCAAAA AGACGG 46 (2) INFORMATION FOR SEQUENCE NO. 270:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 32 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular (ii) MOLECULA TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE : NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) NAME / KEY: various characters (B) LOCATION 1 ... 32 (xi) SEQUENCE DESCRIPTION: Sequence no. 270:

CCGGAATTCG GAGCCAATAG GGAGCTAAAG CC

390 (2) INFORMATION FOR SEQUENCE NO. 271:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 31 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular (ii) MOLECULAR TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE : NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) NAME / KEY: various characters (B) LOCATION 1 ... 31 (xi) SEQUENCE DESCRIPTION: Sequence no. 271:

CGGGATCCGA AGGTGATGGT GTTTATATAG G 31 (2) INFORMATION FOR SEQUENCE NO. 272:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 32 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular (ii) MOLECULA TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE : NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) TITLE / KEY: different characters

391 (B) LOCATION 1 ... 32 (xi) SEQUENCE DESCRIPTION: Sequence no. 272:

CGCATATGGA AGGTGATGGT GTTTATATAG GG 32 (2) INFORMATION FOR SEQUENCE NO. 273:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 37 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular (ii) MOLECULAR TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE : NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) NAME / KEY: different characters (B) LOCATION 1 ... 37 (xi) SEQUENCE DESCRIPTION: Sequence ô. 273:

GCGAATTCTC ACTCTTTCCA ATAGTTTGCT GCAGAGC 37 (2) SEQ ID NO. 274:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 37 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular (ii) MOLECULAR TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE : NOT

392 (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (Ix) SIGN: (A) TITLE / KEY: different characters (B) LOCATION 1 ... 37 (Xi) SEQUENCE DESCRIPTION: Seq. 274:

CCGGAATTCT TAATCCCGTT TCAAATGGTA ATAAAGG 37 (2) SEQ ID NO. 275:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 36 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular (ii) MOLECULAR TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE : NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) NAME / KEY: various characters (B) LOCATION 1 ... 36 (xi) SEQUENCE DESCRIPTION: Sequence no. 275:

GCGAATTCCC TTTTATTTAA AAAGTGTAGT TATACC

7ÍZ

393

Claims (108)

An isolated nucleic acid comprising a nucleotide sequence encoding an H. pylori polypeptide at least about 60% homologous to an amino acid sequence selected from the group consisting of SEQ ID NO: 2. 102, 108, 111, 121, 123, 125, 133, 139, 148, 149, 176 and 177. The isolated nucleic acid of claim 1 comprising a nucleotide sequence selected from the group consisting of SEQ ID NO: 2. 5, 11, 14, 26, 28, 36, 42, 51, 52 and 79 or their complement. 3. an isolated nucleic acid having a nucleotide sequence that encodes an H. pylori polypeptide of at least about 60% homology to an amino acid sequence selected from the group consisting of SEQ ID NO: 2; 98 to 194. 4. An isolated nucleic acid having a nucleotide sequence that encodes a H. pylori polypeptide selected from the group consisting of SEQ ID NO: 2. 98 to 194. An isolated nucleic acid that encodes a H. pylori polypeptide having a nucleotide sequence at least about 60% homologous to a nucleotide sequence selected from the group consisting of SEQ ID NO: 2. 1 to 97 or their supplement. The isolated nucleic acid of claim 3 comprising a nucleotide sequence selected from the group consisting of SEQ ID NO: 2. 1 to 97 or their additions. An isolated nucleic acid molecule that encodes a H. pylori polypeptide with a nucleotide sequence that hybridizes under stringent hybridization conditions to a nucleic acid molecule with a nucleotide sequence selected from the group consisting of SEQ ID NO: 2. 1 to 97 or their additions. 394 An isolated nucleic acid having a nucleotide sequence of at least 8 nucleotides in length, which sequence hybridizes under stringent hybridization conditions to a nucleic acid with a nucleotide sequence selected from the group consisting of SEQ ID NO: 2. 1 to 97 or their supplement. An isolated nucleic acid having a nucleotide sequence encoding a H. pylori cell envelope polypeptide or fragment thereof, wherein the nucleotide sequence is at least 60% homologous to a nucleotide sequence selected from the group consisting of SEQ ID NO: 2. 63, no. 7, no. 8, no. 9, no. 13, no. 14, no. 23, no. 24, no. 27, no. 28, no. 50, no. 51, no. 61, no. 79, no. 80, no. 84, no. 85, no. 91, no. 94, no. 5, no. 11, no. 26, no. 36, no. 42, no. 52, no. 22, no. 29, no. 30, no. 65, no. 66, no. 48, no. 49, no. 17, no. 18, no. 19, no. 43, no. 44, no. 38, no. 39, no. 1, no. 2, no. 6, no. 34, no. 35, no. 60, no. 69 and no. 83 or their additions. The isolated nucleic acid of claim 9, wherein said H. pylori cell envelope polypeptide or fragment thereof is a polypeptide associated with H. pylori flagella or a fragment thereof encoded by a nucleotide sequence that is at least 60% homologous to SEQ ID NO: 2. 63 or its supplement. The isolated nucleic acid of claim 9, wherein said H. pylori cell envelope polypeptide or fragment thereof is an H. pylori inner membrane polypeptide or fragment thereof encoded by a nucleotide sequence that is at least 60% homologous to a nucleotide sequence selected from the group consisting of sequences. no. 48, no. 49, no. 17, no. 18, no. 19, no. 43, no. 44, no. 38 and no. 39 or their additions. The isolated nucleic acid of claim 11, wherein said H. pylori cell envelope polypeptide or fragment thereof is an H. pylori polypeptide or fragment thereof involved in transport and encoded by a nucleotide sequence that is at least 60% homologous to a nucleotide sequence selected from the group of consisting of sequences no. 48, no. 49, no. 17, no. 18, no. 19, no. 43 and no. 44 or their additions. The isolated nucleic acid of claim 9, wherein said H. pylori cell envelope polypeptide or fragment thereof is an external polypeptide Or a fragment thereof encoded by a nucleotide sequence that is at least 60% homologous to a nucleotide sequence selected from the group consisting of SEQ ID NO: 395. 7, no. 8, no. 9, no. 13, no. 14, no. 23, no. 24, no. 27, no. 28, no. 50, no. 51, no. 61, no. 79, no. 80, no. 84, no. 85, no. 91, no. 94, no. 5, no. 11, no. 26, no. 36, no. 42, no. 52, no. 22, no. 29, no. 30, no. 65 and no. 66 or their additions. The isolated nucleic acid of claim 13, wherein said H. pylori outer membrane polypeptide or fragment thereof is a H. pylori polypeptide with a terminal phenylalanine residue or a fragment thereof encoded by a nucleotide sequence that is at least 60% homologous to a nucleotide sequence selected from the group consisting of from Seq. 7, no. 8, no. 9, no. 11, no. 13, no. 14, no. 23, no. 24, no. 26, no. 27, no. 28, no. 36, no. 42, no. 50, no. 51, no. 52, no. 61, no. 79, no. 80, no. 84, no. 85, no. 91 and no. 94 or their additions. The isolated nucleic acid of claim 14, wherein said H. pylori outer membrane polypeptide or fragment thereof is a H. pylori polypeptide with a terminal phenylalanine residue and a C-terminal tyrosine cluster, or a fragment thereof encoded by a nucleotide sequence that is at least 60% homologous to a nucleotide sequence selected from the group consisting of SEQ ID NOs. 11, no. 26, no. 36, no. 42 and no. 52 or their additions. An isolated nucleic acid having a nucleotide sequence encoding a H. pylori cell envelope polypeptide or fragment thereof, wherein said polypeptide comprises an amino acid sequence that is at least 60% homologous to an amino acid sequence selected from the group consisting of SEQ ID NO: 2. 160, no. 104, no. 105, no. 106, no. 110, no. 111, no. 120, no. 121, no. 124, no. 125, no. 147, no. 148, no. 158, no. 176, no. 177, no. 181, no. 182, no. 188, no. 191, no. 102, no. 108, no. 123, no. 133, no. 139, no. 149, no. 119, no. 126, no. 127, no. 162, no. 163, no. 145, no. 146, no. 114, no. 115, no. 116, no. 140, no. 141, no. 135, no. 136, no. 98, no. 99, no. 103, no. 131, no. 132, no. 157, no. 166 and no. 180th The isolated nucleic acid of claim 16, wherein said H. pylori cell envelope polypeptide or fragment thereof is a flagellin-associated polypeptide. 396 H. pylori, or a fragment thereof comprising an amino acid sequence that is at least 60% homologous to SEQ. 160th The isolated nucleic acid of claim 16, wherein said H. pylori cell envelope polypeptide or fragment thereof is an H. pylori inner membrane polypeptide or fragment thereof comprising an amino acid sequence that is at least 60% homologous to a sequence selected from the group consisting of SEQ ID NO: 2. 145, no. 146, no. 114, no. 115, no. 116, no. 140, no. 141, no. 135 and no. 136th The isolated nucleic acid of claim 18, wherein said H. pylori inner membrane polypeptide or fragment thereof is H. pylori polypeptide or a fragment thereof involved in transport comprising an amino acid sequence that is at least 60% homologous to a sequence selected from the group consisting of SEQ ID NO. 145, no. 146, no. 114, no. 115, no. 116, no. 140 and no. 141st The isolated nucleic acid of claim 16, wherein said H. pylori cell envelope polypeptide or fragment thereof is an H. pylori outer membrane polypeptide or fragment thereof comprising an amino acid sequence that is at least 60% homologous to a sequence selected from the group consisting of SEQ ID NO: 2. . 104, no. 105, no. 106, no. 110, no. 111, no. 120, no. 121, no. 124, no. 125, no. 147, no. 148, no. 158, no. 176, no. 177, no. 181, no. 182, no. 188, no. 191, no. 102, no. 108, no. 123, no. 133, no. 139, no. 149, no. 119, no. 126, no. 127, no. 162 and no. 163rd The isolated nucleic acid of claim 20, wherein said H. pylori outer membrane polypeptide or fragment thereof is a H. pylori polypeptide with a terminal phenylalanine residue or a fragment thereof comprising an amino acid sequence that is at least 60% homologous to a sequence selected from the group consisting of SEQ ID NO. 104, no. 105, no. 106, no. 108, no. 110, no. 111, no. 120, no. 121, no. 123, no. 124, no. 125, no. 133, no. 139, no. 147, no. 148, no. 149, no. 158, no. 176, no. 177, no. 181, no. 182, no. 188 and no. 191st 397 The isolated nucleic acid of claim 21, wherein said H. pylori outer membrane polypeptide or fragment thereof is an H. pylori polypeptide with a terminal phenylalanine residue and a C-terminal tyrosine cluster, or a fragment thereof comprising an amino acid sequence that is at least 60% homologous to a sequence selected from the group consisting of Seq. 108, no. 123, no. 133, no. 139 and no. 149th An isolated nucleic acid having a nucleotide sequence encoding a cytoplasmic H. pylori polypeptide or fragment thereof, wherein the nucleotide sequence is at least 60% homologous to a nucleotide sequence selected from the group consisting of SEQ ID NO: 2. 57, no. 58, no. 86, no. 87, no. 88, no. 89, no. 92 and no. 93 or their supplement. The isolated nucleic acid of claim 23, wherein said cytoplasmic H. pylori polypeptide or fragment thereof is an H. pylori polypeptide or fragment thereof involved in mRNA translation, wherein the nucleotide sequence is at least 60% homologous to a nucleotide sequence selected from mRNA. group consisting of sequence no. 57 and no. 58 or their supplement. The isolated nucleic acid of claim 23, wherein said cytoplasmic H. pylori polypeptide or fragment thereof is an H. pylori polypeptide or fragment thereof involved in genomic replication, transcription, recombination, and repair, wherein the nucleotide sequence is at least 60% homologous to the nucleotide a sequence selected from the group consisting of SEQ ID NOs. 86 and no. 87 or their additions. An isolated nucleic acid comprising a nucleotide sequence encoding a cytoplasmic H. pylori polypeptide, or fragment thereof, wherein said polypeptide comprises an amino acid sequence that is at least 60% homologous to a sequence selected from the group consisting of SEQ ID NO: 2. 154, no. 155, no. 183, no. 184, no. 185, no. 186, no. 189 and no. 190th The isolated nucleic acid of claim 26, wherein said cytoplasmic H. pylori polypeptide or fragment thereof is H. 398 pylori or a fragment thereof involved in the translation of an mRNA comprising an amino acid sequence that is at least 60% homologous to a sequence selected from the group consisting of SEQ ID NO. 154 and no. 155th The isolated nucleic acid of claim 26, wherein said cytoplasmic H. pylori polypeptide or fragment thereof is an H. pylori polypeptide or fragment thereof involved in genomic replication, transcription, recombination, and repair, comprising an amino acid sequence that is at least 60% homologous. with a sequence selected from the group consisting of Seq. 183 and no. 184th An isolated nucleic acid comprising a nucleotide sequence encoding a H. pylori secreted polypeptide, or fragment thereof, wherein the nucleotide sequence is at least 60% homologous to a nucleotide sequence selected from the group consisting of SEQ ID NO: 2. 3, no. 4, no. 10, no. 12, no. 20, no. 25, no. 31, no. 32, no. 45, no. 46, no. 53 č. 64, no. 67, no. 70, no. 77, no. 78, no. 81, no. 82, no. 90, no. 95 and no. 97 or their additions. An isolated nucleic acid having a nucleotide sequence encoding a H. pylori secreted polypeptide or fragment thereof, wherein the polypeptide comprises an amino acid sequence that is at least 60% homologous to an amino acid sequence selected from the group consisting of SEQ ID NO: 2. 100, no. 101, no. 107, no. 109, no. 117, no. 122, no. 128, no. 129, no. 142, no. 143, no. 150 č. 161, no. 164, no. 167, no. 174, no. 175, no. 178, no. 179, no. 187, no. 192 and no. 194th An isolated nucleic acid having a nucleotide sequence encoding a H. pylori cell polypeptide, or fragment thereof, wherein the nucleotide sequence is at least 60% homologous to a nucleotide sequence selected from the group consisting of SEQ ID NO: 2. 15, no. 16, no. 21, no. 33, no. 37, no. 40, no. 41, no. 47, no. 54, no. 55, no. 56 č. 59, no. 62, no. 68, no. 71, no. 72, no. 73, no. 74, no. 75, no. 76 and no. 96 or their additions. An isolated nucleic acid having a nucleotide sequence encoding a H. pylori cell polypeptide or fragment thereof, said polypeptide comprising 399 amino acid sequence that is at least 60% homologous to an amino acid sequence selected from the group consisting of SEQ ID NOs. 112, no. 113, no. 118, no. 130, no. 134, no. 137, no. 138, no. 144, no. 151, no. 152, no. 153 č. 156, no. 159, no. 165, no. 168, no. 169, no. 170, no. 171, no. 172, no. 173 and no. 193rd The isolated nucleic acid of any one of claims 1 to 32, wherein the nucleotide sequence contained in the nucleic acid is at least 70%, 80%, 90%, 95%, 98%, or 99% homologous to, or identical to, the selected nucleotide sequence. a selected nucleotide sequence. 34. A probe having a nucleotide sequence consisting of at least 8 nucleotides with a nucleotide sequence selected from the group consisting of SEQ ID NOs. 1 to no. 97 or their additions. A recombinant expression vector comprising the nucleic acid of any one of claims 1 to 33, wherein the nucleic acid comprises a transcriptional regulatory element operably linked to a nucleotide sequence comprised in the nucleic acid. 36. A cell comprising the recombinant expression vector of claim 35. 37. A method for producing a H. pylori polypeptide, comprising culturing the cell of claim 36 under conditions that allow expression of the polypeptide. 38. The method of claim 37, further comprising purifying the polypeptide from the cell. 39. A method for detecting the presence of Helicobacter nucleic acid in a sample comprising the steps of: 400 (a) contacting the sample with the nucleic acid of any one of claims 1 to 34 so that a hybrid can be formed between the probe and the Helicobacter nucleic acid in the sample; and (b) detecting the hybrid formed in step (a), wherein the detection of the hybrid indicates the presence of the Helicobacter nucleic acid in the sample. 40. An isolated H. pylori polypeptide comprising an amino acid sequence at least about 60% homologous to an H. pylori polypeptide selected from the group consisting of SEQ ID NOs. 102, 108, 111, 121, 123, 125, 133, 139, 148, 149, 176 and 177. 41. An isolated H. pylori polypeptide that is encoded by a nucleic acid comprising a nucleotide sequence at least about 60% homologous to a nucleotide sequence selected from the group consisting of SEQ ID NOs. 5, 11, 14, 26, 28, 36, 42, 51, 52 and 79. 42. An isolated H. pylori polypeptide having an amino acid sequence of at least about 60% homologous to an H. pylori polypeptide selected from the group consisting of SEQ ID NOs. 98 to no. 194th 43. An isolated H. pylori polypeptide that is encoded by a nucleic acid having a nucleotide sequence at least about 60% homologous to a nucleotide sequence selected from the group consisting of SEQ ID NO: 2. 1 to 97. 44. The isolated H. pylori polypeptide of claim 43, wherein said polypeptide is encoded by a nucleotide sequence selected from the group consisting of SEQ ID NO: 2. 1 to no. 97th 45. An isolated H. pylori polypeptide that is encoded by a nucleic acid that hybridizes under stringent hybridization conditions to a nucleic acid selected from the group consisting of SEQ ID NO: 2. 1 to 97 or their additions. 46. An isolated H. pylori polypeptide comprising an amino acid sequence selected from the group consisting of SEQ ID NOs. 97 to 194. 401 47. An isolated H. pylori cell envelope polypeptide or fragment thereof, wherein the polypeptide comprises an amino acid sequence that is at least 60% homologous to an amino acid sequence selected from the group consisting of SEQ ID NOs. 160, no. 104, no. 105, no. 106, no. 110, no. 111, no. 120, no. 121, no. 124, no. 125, no. 147, no. 148, no. 158, no. 176, no. 177, no. 181, no. 182, no. 188, no. 191, no. 102, no. 108, no. 123, no. 133, no. 139, no. 149, no. 119, no. 126, no. 127, no. 162, no. 163, no. 145, no. 146, no. 114, no. 115, no. 116, no. 140, no. 141, no. 135, no. 136, no. 98, no. 99, no. 103, no. 131, no. 132, no. 157, no. 166 and no. 180th The isolated polypeptide of claim 47, wherein said H. pylori cell envelope polypeptide or fragment thereof is a H. pylori flagell associated polypeptide or fragment thereof comprising an amino acid sequence that is at least 60% homologous to SEQ ID NO: 2. 160th The isolated polypeptide of claim 48, wherein said H. pylori cell envelope polypeptide or fragment thereof is an H. pylori inner membrane polypeptide or fragment thereof and comprises an amino acid sequence that is at least 60% homologous to an amino acid sequence selected from the group consisting of sequences. no. 145, no. 146, no. 114, no. 115, no. 116, no. 140, no. 141, no. 135 and no. 136th The isolated polypeptide of claim 48, wherein said H. pylori inner membrane polypeptide or fragment thereof is H. pylori polypeptide or a fragment thereof participating in a transport comprising an amino acid sequence that is at least 60% homologous to an amino acid sequence selected from the group consisting of SEQ ID NO. 145, no. 146, no. 114, no. 115, no. 116, no. 140 and no. 141st The isolated polypeptide of claim 48, wherein said H. pylori cell envelope polypeptide or fragment thereof is an H. pylori outer membrane polypeptide or fragment thereof comprising an amino acid sequence that is at least 60% homologous to an amino acid sequence selected from the group consisting of SEQ ID NOs. . 104, no. 105, no. 106, no. 110, no. 111, no. 120, no. 121, no. 124, no. 125, no. 147, no. 148, no. 158, no. 176, no. 177, ô. 181, no. 402 182, no. 188, no. 191, no. 102, no. 108, no. 123, no. 133, no. 139, no. 149, no. 119, no. 126, no. 127, no. 162 and no. 163rd The isolated polypeptide of claim 51, wherein said H. pylori outer membrane polypeptide or fragment thereof is an H. pylori polypeptide with a terminal phenylalanine residue or a fragment thereof comprising an amino acid sequence that is at least 60% homologous to an amino acid sequence selected from the group consisting of SEQ ID NO. 104, no. 105, no. 106, no. 108, no. 110, no. 111, no. 120, no. 121, no. 123, no. 124, no. 125, no. 133, no. 139, no. 147, no. 148, no. 149, no. 158, no. 176, no. 177, no. 181, no. 182, no. 188 and no. 191st The isolated polypeptide of claim 52, wherein said H. pylori outer membrane polypeptide or fragment thereof is an H. pylori polypeptide with a terminal phenylalanine residue and a C-terminal tyrosine cluster or a fragment thereof comprising an amino acid sequence that is at least 60% homologous to the amino acid. a sequence selected from the group consisting of Seq. 108, no. 123, no. 133, no. 139 and no. 149th 54. An isolated H. pylori cell envelope polypeptide, or fragment thereof, wherein the polypeptide is encoded by a nucleic acid comprising a nucleotide sequence that is at least 60% homologous to a nucleotide sequence selected from the group consisting of SEQ ID NOs. 63, no. 7, no. 8, no. 9, no. 13, no. 14, no. 23, no. 24, no. 27, no. 28, no. 50, no. 51, no. 61, no. 79, no. 80, no. 84, no. 85, no. 91, no. 94, no. 5, no. 11, no. 26, no. 36, no. 42, no. 52, no. 22, no. 29, no. 30, no. 65, no. 66, no. 48, no. 49, no. 17, no. 18, no. 19, no. 43, no. 44, no. 38, no. 39, no. 1, no. 2, no. 6, no. 34, no. 35, no. 60, no. 69 and no. 83rd The isolated polypeptide of claim 54, wherein said H. pylori cell envelope polypeptide or fragment thereof is a polypeptide associated with H. pylori flagella or a fragment thereof encoded by a nucleic acid comprising a nucleotide sequence that is at least 60% homologous to SEQ ID NO: 2. 63rd The isolated polypeptide of claim 54, wherein said H. pylori cell envelope polypeptide or fragment thereof is an inner membrane polypeptide of H. 403 pylori or a fragment thereof encoded by a nucleic acid comprising a nucleotide sequence that is at least 60% homologous to a nucleotide sequence selected from the group consisting of SEQ ID NO: 40; 48, no. 49, no. 17, no. 18, no. 19, no. 43, no. 44, no. 38 and no. 39th The isolated polypeptide of claim 56, wherein the H. pylori cell envelope polypeptide or fragment thereof is an H. pylori polypeptide or fragment thereof involved in transport and encoded by a nucleic acid comprising a nucleotide sequence that is at least 60% homologous to a nucleotide sequence selected from group consisting of sequence no. 48, no. 49, no. 17, no. 18, 6.19, no. 43 and no. 44th The isolated polypeptide of claim 54, wherein the H. pylori cell envelope polypeptide or fragment thereof is an H. pylori outer membrane polypeptide or fragment thereof encoded by a nucleic acid comprising a nucleotide sequence that is at least 60% homologous to a nucleotide sequence selected from the group consisting of SEQ ID NO. 7, no. 8, no. 9, no. 13, no. 14, no. 23, no. 24, no. 27, no. 28, no. 50, no. 51, no. 61, no. 79, no. 80, no. 84, no. 85, no. 91, no. 94, no. 5, no. 11, no. 26, no. 36, no. 42, no. 52, no. 22, no. 29, no. 30, no. 65 and no. 66th The isolated polypeptide of claim 58, wherein said H. pylori outer membrane polypeptide or fragment thereof is a H. pylori polypeptide with a terminal phenylalanine residue or a fragment thereof encoded by a nucleic acid comprising a nucleotide sequence that is at least 60% homologous to a nucleotide sequence selected from group consisting of sequence no. 7, no. 8, no. 9, no. 11, no. 13, no. 14, no. 23, no. 24, no. 26, no. 27, no. 28, no. 36, no. 42, no. 50, no. 51, no. 52, no. 61, no. 79, no. 80, no. 84, no. 85, no. 91 and no. 94th The isolated polypeptide of claim 59, wherein the H. pylori outer membrane polypeptide or fragment thereof is an H. pylori polypeptide with a terminal phenylalanine residue and a C-terminal tyrosine cluster, or a fragment thereof encoded by a nucleic acid comprising a nucleotide sequence that is at least 60% homologous. having a nucleotide sequence selected from the group consisting of SEQ ID NOs. 11, no. 26, no. 36, no. 42 and no. 52nd 404 61. An isolated cytoplasmic H. pylori polypeptide, or fragment thereof, wherein said polypeptide comprises an amino acid sequence that is at least 60% homologous to an amino acid sequence selected from the group consisting of SEQ ID NOs. 154, no. 155, no. 183, no. 184, no. 185, no. 186, no. 189 and no. 190th The isolated polypeptide of claim 61, wherein said cytoplasmic H. pylori polypeptide or fragment thereof is H. pylori polypeptide or fragment thereof involved in translation of an mRNA comprising an amino acid sequence that is at least 60% homologous to an amino acid sequence selected from the group consisting of SEQ ID NO. 154 and no. 155th 63. The isolated polypeptide of claim 61, wherein said cytoplasmic H. pylori polypeptide or fragment thereof is an H. pylori polypeptide or fragment thereof involved in genomic replication, transcription, recombination, and repair comprising an amino acid sequence that is at least 60% homologous to the amino acid. a sequence selected from the group consisting of Seq. 183 and no. 184th 64. An isolated cytoplasmic H. pylori polypeptide or fragment thereof, wherein said polypeptide is encoded by a nucleic acid comprising a nucleotide sequence that is at least 60% homologous to a nucleotide sequence selected from the group consisting of SEQ ID NO: 2. 57, no. 58, no. 86, no. 87, no. 88, no. 89, no. 92 and no. 93rd 65. The isolated polypeptide of claim 64, wherein said cytoplasmic H. pylori polypeptide or fragment thereof is H. pylori polypeptide or fragment thereof involved in mRNA translation, said polypeptide being encoded by a nucleic acid comprising a nucleotide sequence that is at least 60% homologous having a nucleotide sequence selected from the group consisting of SEQ ID NOs. 57 and no. 58th The isolated polypeptide of claim 64, wherein said cytoplasmic H. pylori polypeptide or fragment thereof is H. pylori polypeptide or fragment thereof involved in genomic replication, transcription, and repair, 405 wherein the polypeptide is encoded by a nucleic acid comprising a nucleotide sequence that is at least 60% homologous to a nucleotide sequence selected from the group consisting of SEQ ID NO: 6; 86 and no. 87th 67. An isolated H. pylori cell polypeptide, or fragment thereof, wherein the polypeptide comprises an amino acid sequence that is at least 60% homologous to an amino acid sequence selected from the group consisting of SEQ ID NOs. 112, no. 113, no. 118, no. 130, no. 134, no. 137, no. 138, no. 144, no. 151, no. 152, no. 153 č. 156, no. 159, no. 165, no. 168, no. 169, no. 170, no. 171, no. 172, no. 173 and no. 193rd 68. An isolated H. pylori cell polypeptide or fragment thereof, wherein the polypeptide comprises an amino acid sequence that is at least 60% homologous to an amino acid sequence that is encoded by a nucleic acid selected from the group consisting of SEQ ID NO: 2. 15, no. 16, no. 21, no. 33, no. 37, no. 40, no. 41, no. 47, no. 54, no. 55, no. 56 č. 59, no. 62, no. 68, no. 71, no. 72, no. 73, no. 74, no. 75, no. 76 and no. 96th 69. An isolated H. pylori secreted polypeptide or fragment thereof, wherein the polypeptide comprises an amino acid sequence that is at least 60% homologous to an amino acid sequence selected from the group consisting of SEQ ID NOs. 100, no. 101, no. 107, no. 109, no. 117, no. 122, no. 128, no. 129, no. 142, no. 143, no. 150 č. 161, no. 164, no. 167, no. 174, no. 175, no. 178, no. 179, no. 187, no. 192 and no. 194th 70. An isolated H. pylori secreted polypeptide or fragment thereof, wherein the polypeptide comprises an amino acid sequence that is at least 60% homologous to an amino acid sequence that is encoded by a nucleic acid selected from the group consisting of SEQ ID NO: 2. 3, no. 4, no. 10, no. 12, no. 20, no. 25, no. 31, no. 32, no. 45, no. 46, no. 53 č. 64, no. 67, no. 70, no. 77, no. 78, no. 81, no. 82, no. 90, no. 95 and no. 97th The isolated polypeptide of any one of claims 40 to 70, wherein the amino acid sequence contained in the isolated polypeptide is at least 70%, 80%, 90%, 95%, 98%, or 99% homologous to the selected polypeptide. 406 amino acid sequence or identical to the selected amino acid sequence. 72. A fusion protein comprising an H. pylori polypeptide which comprises an amino acid sequence that is at least 60% homologous to an amino acid sequence selected from the group consisting of SEQ ID NOs. 98 to no. 194 functionally linked to a non-H. pylori polypeptide. A vaccine composition for the prophylactic or therapeutic treatment of H. pylori infection, comprising an effective amount of at least one isolated nucleic acid according to any one of claims 1 to 33. 74. A vaccine composition for the prophylactic or therapeutic treatment of an H. pylori infection, comprising an effective amount of at least one isolated nucleic acid encoding an H. pylori outer membrane polypeptide or fragment thereof, wherein said nucleic acid comprises a nucleotide sequence that is at least 60% homologous to a nucleotide sequence selected from the group consisting of SEQ ID NOs. 28, no. 50, no. 24, no. 11, no. 52, no. 42 and no. 79th 75. The vaccine composition of claim 74, wherein said nucleic acid comprises a nucleotide sequence that is at least 60% homologous to SEQ ID NO: 2. 52nd 76. The vaccine composition of claim 74 or 75, wherein the nucleotide sequence contained in the nucleic acid is at least 70%, 80%, 90%, 95%, 98%, or 99% homologous to, or identical to, the selected nucleotide sequence. a selected nucleotide sequence. A vaccine composition according to any one of claims 73 to 76, characterized in that it contains genetically engineered attenuated live viruses or bacteria or virus-like recombinant particles. 407 78. A vaccine composition for the prophylactic or therapeutic treatment of an H. pylori infection, comprising an effective amount of at least one H. pylori polypeptide or fragment thereof according to any one of claims 40 to 70. 79. A vaccine composition for the prophylactic or therapeutic treatment of H. pylori infection, comprising an effective amount of at least one H. pylori outer membrane polypeptide or fragment thereof, wherein said polypeptide comprises an amino acid sequence that is at least 60% homologous to the amino acid. a sequence selected from the group consisting of Seq. 125, no. 147, no. 121, no. 108, no. 149, no. 139 and no. 176th 80. The vaccine composition of claim 79, wherein said polypeptide comprises an amino acid sequence that is at least 60% homologous to SEQ ID NO: 2. 149th 81. The vaccine composition of claim 79 or 80, wherein said amino acid sequence contained in the isolated polypeptide is at least 70%, 80%, 90%, 95%, 98%, or 99% homologous to the selected amino acid sequence, or is identical to the selected amino acid sequence. 82. A vaccine composition according to any one of claims 79 to 81 comprising a substance selected from cholera toxin, non-toxic cholera toxin derivatives, procholeragenoid, fungal polysaccharide, muramyl dipeptide, muramyl dipeptide derivative, phorbol ester, E. coli labile toxin, lysate. other than H. pylori bacteria, block polymer, saponin, biodegradable microcapsules, ISCOM, cochleate, liposome, genetic engineering techniques of attenuated viruses or bacteria, and recombinant virus-like particles. 83. The vaccine composition of any one of claims 73 to 82, further comprising a pharmaceutically acceptable carrier. 408 84. The vaccine composition of claim 83, wherein the pharmaceutically acceptable carrier comprises an adjuvant. 85. The vaccine composition of claim 83 or 84, wherein the pharmaceutically acceptable carrier comprises a delivery system. 86. The vaccine composition of claim 85, wherein the delivery system comprises a live vector. 87. The vaccine composition of claim 86, wherein the live vector is a bacterium or a virus. 88. A method of treating or reducing the risk of H. pylori infection in a subject, comprising administering to the subject a vaccine composition according to any one of claims 73 to 87 to treat or reduce the risk of H. pylori infection. 89. A method of making a vaccine composition comprising combining at least one isolated H. pylori polypeptide of claim 42 with a pharmaceutically acceptable carrier to form a vaccine composition. 90. A method of making a vaccine composition comprising the steps of: (a) culturing the cell under conditions that allow expression of the H. pylori polypeptide of claim 42; (b) isolating said H. pylori polypeptide or fragment thereof from said cell; and (c) combining at least one of said isolated H. pylori polypeptide or fragment thereof with a pharmaceutically acceptable carrier to form a vaccine preparation. 91. A chimeric H. pylori polypeptide comprising the amino acid sequences of at least two H. pylori polypeptides or fragments thereof, characterized by: 409, wherein said polypeptides are encoded by nucleic acid sequences as defined in claim 5. 92. A chimeric H. pylori polypeptide comprising at least two H. pylori polypeptides or fragments thereof, wherein each of said polypeptides is in accordance with claim 42. Use of an isolated nucleic acid according to any one of claims 1 to 33 for the manufacture of a vaccine composition for treating H. pylori infection in a subject. Use of the purified polypeptide of any one of claims 40 to 71 for the manufacture of a vaccine composition for treating H. pylori infection in a subject. Use according to claim 93 or 94, wherein the treatment is a prophylactic treatment. The use of claim 93 or 94, wherein the treatment is a therapeutic treatment. 97. A drug screening process comprising contacting a test compound with a purified polypeptide comprising an amino acid sequence that is at least 60% homologous to the amino acid sequence shown in the sequence listing. 98. The method of claim 97, comprising determining whether the compound binds to said amino acid sequence of a purified polypeptide. 99. The method of claim 97 or 98, comprising determining whether a test compound alters the binding activity of said amino acid sequence of a purified polypeptide to its ligand. 100. The method of claim 99, wherein determining the test compound inhibits the ability of said amino acid sequence to bind to a ligand. 410 101. The method of claim 97 or 98, wherein the polypeptide has enzymatic activity, comprising determining whether the test compound alters the enzymatic activity. 102. The method of claim 10, wherein the enzymatic activity produces a detectable product with characteristic absorption, fluorescence, or chemiluminescence properties. A method according to any one of claims 97 to 102, characterized in that it is cell-free. The method of any one of claims 97 to 103, wherein the amino acid sequence contained in the purified polypeptide is at least 70%, 80%, 90%, 95%, 98%, or 99% homologous to the amino acid sequence set forth in the Sequence Listing. or is identical to the amino acid sequence shown in the sequence listing. 105. A drug screening process comprising the step of contacting a test compound with an isolated nucleic acid comprising a nucleotide sequence that is at least 60% homologous to the nucleotide sequence set forth in the Sequence Listing. 106. The method of claim 105, comprising determining whether the compound binds to or interacts with said nucleotide sequence of the nucleic acid. 107. The method of claim 105, wherein the method is an in vitro method. 108. The method of any one of claims 105 to 107, wherein the nucleotide sequence contained in the nucleic acid is at least 70%, 80%, 90%, 95%, 98%, or 99% homologous to the nucleotide sequence set forth in the Sequence Listing. or is identical to the nucleotide sequence set forth in the Sequence Listing.