SK34699A3 - 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.

Description

Nucleotides and amino acid sequences related to Helicobacter pylon and vaccine compositions containing them

BACKGROUND OF THE INVENTION

Helicobacter pylori is a gram-negative, microaerophilic, S-shaped bacterium that has been discovered and cultured from a biopsy sample of human stomach. (Warren, J.R. and B. Marshall, (1983) Lancet 1: 1273-1275; and Marshall et al., (1984) Microbios Lett. 25: 83-88). H. pylori has been 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 virulence factors include the following: urease, an enzyme that can 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. (Hazell 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); 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. pylori infections in vitro are currently available. (Huesca et.ai., (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 accessibility. (Hopkins, R.J. and J.G. Morris, supra). Part of the standard regimen used to treat H. pylori 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 ameliorate 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 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 to screen for compounds with the ability to interfere with the H. pylori life cycle or inhibit H. pylori infection. 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 for the detection of H. pylori infection. In addition, the present invention encompasses vaccine compositions and methods of protecting or treating H. pylori infection.

DETAILED DESCRIPTION OF THE INVENTION

In one aspect, the invention relates to a recombinant or substantially pure preparation of H. pylori polypeptide of SEQ. no. 74. The invention also encompasses a substantially pure nucleic acid encoding an H. pylori polypeptide of SEQ. no. 74, wherein such nucleic acid is comprised in SEQ. no. 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 an H. pylori polypeptide having amino acid sequence # 1. 75, such as a nucleic acid comprising nucleotide sequence no. Second

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

In another aspect, the invention relates to a substantially pure nucleic acid that encodes an H. pylori polypeptide having amino acid sequence # 1. 77, such as a nucleic acid comprising nucleotide sequence no. 4th

In another aspect, the invention relates to a substantially pure nucleic acid that encodes an H. pylori polypeptide having amino acid sequence # 1. 78, such as a nucleic acid comprising nucleotide sequence no. 5th

In another aspect, the invention relates to a substantially pure nucleic acid that encodes an H. pylori polypeptide having amino acid sequence # 1. 79, such as a nucleic acid comprising nucleotide sequence no. 6th

In another aspect, the invention relates to a substantially pure nucleic acid that encodes an H. pylori polypeptide having amino acid sequence # 1. 80, 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. pylori polypeptide having amino acid sequence # 1. 81, 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. pylori polypeptide having amino acid sequence # 1. 82, such as a nucleic acid comprising nucleotide sequence no. 9th

In another aspect, the invention relates to a substantially pure nucleic acid that encodes an H. pylori polypeptide having amino acid sequence # 1. 83, such as a nucleic acid comprising nucleotide sequence no. 10th

In another aspect, the invention relates to a substantially pure nucleic acid that encodes an H. pylori polypeptide having amino acid sequence # 1. 84, such as a nucleic acid comprising nucleotide sequence no. 11th

In another aspect, the invention relates to a substantially pure nucleic acid that encodes an H. pylori polypeptide having amino acid sequence # 1. 85, 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. pylori polypeptide having amino acid sequence # 1. 86, such as a nucleic acid comprising nucleotide sequence no. 13th

In another aspect, the invention relates to a substantially pure nucleic acid that encodes an H. pylori polypeptide having amino acid sequence # 1. 87, such as a nucleic acid comprising nucleotide sequence no. 14th

In another aspect, the invention relates to a substantially pure nucleic acid that encodes an H. pylori polypeptide having amino acid sequence # 1. 88, 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. pylori polypeptide having amino acid sequence # 1. 89, such as a nucleic acid comprising nucleotide sequence no. 16th

In another aspect, the invention relates to a substantially pure nucleic acid that encodes an H. pylori polypeptide having amino acid sequence # 1. 90, such as a nucleic acid comprising nucleotide sequence no. 17th

In another aspect, the invention relates to a substantially pure nucleic acid that encodes an H. pylori polypeptide having amino acid sequence # 1. 91, 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. pylori polypeptide having amino acid sequence # 1. 92, such as a nucleic acid comprising nucleotide sequence no. 19th

In another aspect, the invention relates to a substantially pure nucleic acid that encodes an H. pylori polypeptide having amino acid sequence # 1. 93, such as a nucleic acid comprising nucleotide sequence no. 20th

In another aspect, the invention relates to a substantially pure nucleic acid that encodes an H. pylori polypeptide having amino acid sequence # 1. 94, 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. pylori polypeptide having amino acid sequence # 1. 95, such as a nucleic acid comprising nucleotide sequence no. 22nd

In another aspect, the invention relates to a substantially pure nucleic acid that encodes an H. pylori polypeptide having amino acid sequence # 1. 96, such as a nucleic acid comprising nucleotide sequence no. 23rd

In another aspect, the invention relates to a substantially pure nucleic acid that encodes an H. pylori polypeptide having amino acid sequence # 1. 97, such as a nucleic acid comprising nucleotide sequence no. 24th

In another aspect, the invention relates to a substantially pure nucleic acid that encodes an H. pylori polypeptide having amino acid sequence # 1. 98, such as a nucleic acid comprising nucleotide sequence no. 25th

In another aspect, the invention relates to a substantially pure nucleic acid that encodes an H. pylori polypeptide having amino acid sequence # 1. 99, such as a nucleic acid comprising nucleotide sequence no. 26th

In another aspect, the invention relates to a substantially pure nucleic acid that encodes an H. pylori polypeptide having amino acid sequence # 1. 100, such as a nucleic acid comprising nucleotide sequence no. 27th

In another aspect, the invention relates to a substantially pure nucleic acid that encodes an H. py / oral polypeptide having amino acid sequence # 1. 101, such as a nucleic acid comprising nucleotide sequence no. 28th

In another aspect, the invention relates to a substantially pure nucleic acid that encodes an H. pylori polypeptide having amino acid sequence # 1. 102, such as a nucleic acid comprising nucleotide sequence no. 29th

In another aspect, the invention relates to a substantially pure nucleic acid that encodes an H. pylori polypeptide having amino acid sequence # 1. 103, 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. pylori polypeptide having amino acid sequence # 1. 104, 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. pylori polypeptide having amino acid sequence # 1. 105, 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. pylori polypeptide having amino acid sequence # 1. 106, 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. pylori polypeptide having amino acid sequence # 1. 107, such as a nucleic acid comprising nucleotide sequence no. 34th

In another aspect, the invention relates to a substantially pure nucleic acid that encodes an H. pylon polypeptide having amino acid sequence # 1. 108, such as a nucleic acid comprising nucleotide sequence no. 35th

In another aspect, the invention relates to a substantially pure nucleic acid that encodes an H. py / ori polypeptide having amino acid sequence # 1. 109, such as a nucleic acid comprising nucleotide sequence no. 36th

In another aspect, the invention relates to a substantially pure nucleic acid that encodes an H. pylori polypeptide having amino acid sequence # 1. 110, such as a nucleic acid comprising nucleotide sequence no. 37th

In another aspect, the invention relates to a substantially pure nucleic acid that encodes an H. pylon polypeptide having amino acid sequence # 1. 111, such as a nucleic acid comprising nucleotide sequence no. 38th

In another aspect, the invention relates to a substantially pure nucleic acid that encodes an H. pylori polypeptide having amino acid sequence # 1. 112, 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. pylori polypeptide having amino acid sequence # 1. 113, such as a nucleic acid comprising nucleotide sequence no. 40th

In another aspect, the invention relates to a substantially pure nucleic acid that encodes an H. pylori polypeptide having amino acid sequence # 1. 114, 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. pylori polypeptide having amino acid sequence # 1. 115, such as a nucleic acid comprising nucleotide sequence no. 42nd

In another aspect, the invention relates to a substantially pure nucleic acid that encodes an H. pylori polypeptide having amino acid sequence # 1. 116, 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. pylori polypeptide having amino acid sequence # 1. 117, such as a nucleic acid comprising nucleotide sequence no. 44th

In another aspect, the invention relates to a substantially pure nucleic acid that encodes an H. py / oral polypeptide having amino acid sequence # 1. 118, such as a nucleic acid comprising nucleotide sequence no. 45th

In another aspect, the invention relates to a substantially pure nucleic acid that encodes an H. pylori polypeptide having amino acid sequence # 1. 119, such as a nucleic acid comprising nucleotide sequence no. 46th

In another aspect, the invention relates to a substantially pure nucleic acid that encodes an H. pylori polypeptide having amino acid sequence # 1. 120, such as a nucleic acid comprising nucleotide sequence no. 47th

In another aspect, the invention relates to a substantially pure nucleic acid that encodes an H. pylori polypeptide having amino acid sequence # 1. 121, such as a nucleic acid comprising nucleotide sequence no. 48th

In another aspect, the invention relates to a substantially pure nucleic acid that encodes an H. pylori polypeptide having amino acid sequence # 1. 122, such as a nucleic acid comprising nucleotide sequence no. 49th

In another aspect, the invention relates to a substantially pure nucleic acid that encodes an H. pylori polypeptide having amino acid sequence # 1. 123, 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. pylori polypeptide having amino acid sequence # 1. 124, 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. pylori polypeptide having amino acid sequence # 1. 125, such as a nucleic acid comprising nucleotide sequence no. 52nd

In another aspect, the invention relates to a substantially pure nucleic acid that encodes an H. pylori polypeptide having amino acid sequence # 1. 126, such as a nucleic acid comprising nucleotide sequence no. 53rd

In another aspect, the invention relates to a substantially pure nucleic acid that encodes an H. pylori polypeptide having amino acid sequence # 1. 127, such as a nucleic acid comprising nucleotide sequence no. 54th

In another aspect, the invention relates to a substantially pure nucleic acid that encodes an H. pylori polypeptide having amino acid sequence # 1. 128, such as a nucleic acid comprising nucleotide sequence no. 55th

In another aspect, the invention relates to a substantially pure nucleic acid that encodes an H. pylori polypeptide having amino acid sequence # 1. 129, 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. pylori polypeptide having amino acid sequence # 1. 130, 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. 131, 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. pylori polypeptide having amino acid sequence # 1. 132, such as a nucleic acid comprising nucleotide sequence no. 59th

In another aspect, the invention relates to a substantially pure nucleic acid that encodes an H. pylori polypeptide having amino acid sequence # 1. 133, 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. 134, 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. pylon polypeptide having amino acid sequence # 1. 135, such as a nucleic acid comprising nucleotide sequence no. 62nd

In another aspect, the invention relates to a substantially pure nucleic acid that encodes an H. pylori polypeptide having amino acid sequence # 1. 136, such as a nucleic acid comprising nucleotide sequence no. 63rd

In another aspect, the invention relates to a substantially pure nucleic acid that encodes an H. pylori polypeptide having amino acid sequence # 1. 137, such as a nucleic acid comprising nucleotide sequence no. 64th

In another aspect, the invention relates to a substantially pure nucleic acid that encodes an H. pylori polypeptide having amino acid sequence # 1. 138, 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. pylori polypeptide having amino acid sequence # 1. 139, 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. pylori polypeptide having amino acid sequence # 1. 140, such as a nucleic acid comprising nucleotide sequence no. 67th

In another aspect, the invention relates to a substantially pure nucleic acid that encodes an H. pylori polypeptide having amino acid sequence # 1. 141, such as a nucleic acid comprising nucleotide sequence no. 68th

In another aspect, the invention relates to a substantially pure nucleic acid that encodes an H. pylori polypeptide having amino acid sequence # 1. 142, such as a nucleic acid comprising nucleotide sequence no. 69th

In another aspect, the invention relates to a substantially pure nucleic acid that encodes an H. pylori polypeptide having amino acid sequence # 1. 143, such as a nucleic acid comprising nucleotide sequence no. 70th

II

In another aspect, the invention relates to a substantially pure nucleic acid that encodes an H. pylon polypeptide having amino acid sequence # 1. 144, such as a nucleic acid comprising nucleotide sequence no. 71st

In another aspect, the invention relates to a substantially pure nucleic acid that encodes an H. pylon polypeptide having amino acid sequence # 1. 145, such as a nucleic acid comprising nucleotide sequence no. 72nd

In another aspect, the invention relates to a substantially pure nucleic acid that encodes an H. py / ori polypeptide having amino acid sequence # 1. 146, such as a nucleic acid comprising nucleotide sequence no. 73rd

In particular, an isolated nucleic acid comprising a nucleotide sequence encoding an H. pylon cell envelope polypeptide or fragment thereof is preferred. Such nucleic acid is selected from the group consisting of SEQ. no. 3, SEQ. no. 25, SEQ. no. 48, SEQ. no. 16, SEQ. no. 10, SEQ. no. 45, Seq. no. 35, SEQ. no. 37, SEQ. no. 7, SEQ. no. 39, SEQ. no. 55, Seq. no. 18, SEQ. no. 19, SEQ. no. 28, SEQ. no. 30, SEQ. no. 52, SEQ. no. 54, SEQ. no. 56, Seq. no. 58, Seq. no. 1, SEQ. no. 42, SEQ. no. 14, SEQ. no. 43, Seq. no. 11, SEQ. no. 71, Seq. no. 17, SEQ. no. 57, SEQ. no. 5, SEQ. no. 6, SEQ. no. 8 and SEQ. no. 21st

In another embodiment, the H. pylori cell envelope polypeptide or fragment thereof is a H. pylon inner membrane polypeptide or fragment thereof encoded by a nucleic acid selected from the group consisting of SEQ. no. 3, SEQ. no. 25 and SEQ. no. 48th

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. no. 16, SEQ. no. 10, SEQ. no. 45, Seq. no. 35, SEQ. no. 37, Seq. no. 7, SEQ. no. 39, SEQ. no. 55, Seq. no. 18, SEQ. no. 19, SEQ. no. 28, SEQ. no. 30, SEQ. no. 52, SEQ. no. 54, SEQ. no. 56, Seq. no. 58, Seq. no. 1, SEQ. no. 42, SEQ. 14, no. SEQ. 43, no. SEQ. 11 and no. SEQ. no. 71st

In another embodiment, the H. pylori outer membrane polypeptide or fragment thereof is H. pylori polypeptide having a terminal phenylalanine residue and

A C-terminal tyrosine cluster, or fragment thereof, encoded by a nucleic acid selected from the group consisting of SEQ. no. 1, SEQ. no. 42, SEQ. no. 14, SEQ. no. 43, Seq. no. 11 and SEQ. no. 71st

In yet another embodiment, the H. pylori outer membrane polypeptide or fragment thereof is H. pylori polypeptide having a terminal phenylalanine residue or fragment thereof encoded by a nucleic acid selected from the group consisting of SEQ. no. 16, SEQ. no. 45, Seq. no. 35, SEQ. no. 37, Seq. no. 7, SEQ. no. 39, SEQ. no. 55, Seq. no. 18, SEQ. no. 19, SEQ. no. 28, SEQ. no. 30, SEQ. no. 52, SEQ. no. 54, SEQ. no. 56 and SEQ. no. 58th

In particular, an isolated nucleic acid comprising a nucleotide sequence that encodes a H. pylori secretory polypeptide or fragment thereof is preferred. Such nucleic acid is selected from the group consisting of SEQ. no. 72, Seq. no. 32, Seq. no. 51, Seq. no. 2, SEQ. no. 4, SEQ. no. 9, SEQ. no. 13, SEQ. no. 22, SEQ. no. 29, Seq. no. 31, Seq. no. 33, SEQ. no. 34, SEQ. no. 36, Seq. no. 38, SEQ. no. 40, SEQ. no. 41, Seq. no. 44, Seq. no. 46, Seq. no. 49, SEQ. no. 53, SEQ. no. 59, SEQ. no. 61, Seq. no. 62, Seq. no. 63, Seq. no. 65, Seq. no. 66, Seq. no. 67 and SEQ. no. 68th

In particular, an isolated nucleic acid comprising a nucleotide sequence that encodes an H. pylori cell polypeptide or fragment thereof is preferred. Such nucleic acid is selected from the group consisting of SEQ. no. 12, SEQ. no. 15, SEQ. no. 20, SEQ. no. 23, SEQ. no. 24, SEQ. no. 26, SEQ. no. 27, SEQ. no. 47, Seq. no. 50, SEQ. no. 60, SEQ. no. 64, Seq. no. 69, Seq. no. 70 and SEQ. no. 73rd

Particularly preferred is a purified or isolated H. pylori cell polypeptide or fragment thereof wherein the polypeptide is selected from the group consisting of SEQ. no. 76, Seq. no. 98, Seq. no. 121, Seq. no. 89, Seq. no. 83, Seq. no. 118, Seq. no. 108, Seq. no. 110, Seq. no. 80, SEQ. no. 112, Seq. no. 128, Seq. no. 91, Seq. no. 92, SEQ. no. 101, SEQ. no. 103, SEQ. no. 125, Seq. no. 127, Seq. no. 129, SEQ. no. 131, SEQ. no. 74, Seq. no. 115, Seq. no. 87, Seq. no. 116, Seq. no. SEQ. no. 84, SEQ. no. 144, Seq. no. 90, Seq. no. 130, SEQ. no. 78, SEQ. no. 79, Seq. no. 81 and SEQ. no. 94th

In another embodiment, the H. pylon is a cell envelope polypeptide or fragment thereof, an H. pylori inner membrane polypeptide or fragment thereof, selected from the group consisting of SEQ. no. 76, Seq. no. 98 and SEQ. no. 121st

In another embodiment, H. pylori is a cell envelope polypeptide or fragment thereof, H. pylori outer membrane polypeptide or fragment thereof, selected from the group consisting of SEQ. no. 89, Seq. no. 83, Seq. no. 118, Seq. no. 108, Seq. no. 110, Seq. no. 80, SEQ. no. 112, Seq. no. 128, Seq. no. 91, Seq. no. 92, SEQ. no. 101, SEQ. no. 103, SEQ. no. 125, Seq. no. 127, Seq. no. 129, SEQ. no. 131, SEQ. no. 74, Seq. no. 115, Seq. no. 87, Seq. no. 116, Seq. no. 84, SEQ. no. 144, Seq. no. 90 and SEQ. no. 130th

In another embodiment, the H. pylori polypeptide is an outer membrane polypeptide or fragment thereof, a H. pylori polypeptide having a terminal phenylalanine residue, and a C-terminal tyrosine cluster, or fragment thereof, selected from the group consisting of SEQ. no. 74, Seq. no. 115, Seq. no. 87, Seq. no. 116, Seq. no. 84 and SEQ. no. 144th

In another embodiment, the H. pylori polypeptide is an outer membrane polypeptide or fragment thereof, a H. pylori polypeptide having a terminal phenylalanine residue, or a fragment thereof, selected from the group consisting of SEQ. no. 89, Seq. no. 118, Seq. no. 108, Seq. no. 110, Seq. no. 80, SEQ. no. 112, Seq. no. 128, Seq. no. 91, Seq. no. 92, SEQ. no. 101, SEQ. no. 103, SEQ. no. 125, Seq. no. 127, Seq. no. 129 and SEQ. no. 131st

Particularly preferred is a purified or isolated H. pylori secretory polypeptide or fragment thereof, wherein the polypeptide is selected from the group consisting of SEQ. no. 145, Seq. no. 105, Seq. no. 124, Seq. no. 75, Seq. no. 77, Seq. no. 82, SEQ. no. 86, Seq. no. 95, Seq. no. 102, SEQ. no. 104, SEQ. no. 106, SEQ. no. 107, SEQ. no. 109, Seq. no. 111, Seq. no. 113, SEQ. no. 114, SEQ. no. 117, Seq. no. 119, Seq. no. 122, SEQ. no. 126, SEQ. no. 132, Seq. no. 134, Seq. no. 135, Seq. no. 136, SEQ. no. 138, Seq. no. 139, Seq. no. 140 and SEQ. no. 141st

Particularly preferred is a purified or isolated H. pylori cell polypeptide or fragment thereof, wherein the polypeptide is selected from the group consisting of SEQ. no. 85, SEQ. no. 88, Seq. no. 93, SEQ. no. 96, Seq. no. 97, Seq. no. 99, Seq. no. 100, SEQ. no. 120, SEQ. no. 123, Seq. no. 133, SEQ. no. 137, Seq. no. 142, Seq. no. 143 and SEQ. no. 146th

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

In another aspect, the invention provides nucleic acids capable of binding to H. pylori mRNA. Such a nucleic acid is capable of acting as an antisense nucleic acid to control the translation 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 are useful as probes to capture reagents.

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 for the production of 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 assess the amount and distribution of H. py / on-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. fragment of a host cell polypeptide, to bind 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 bacterial life cycle activators or inhibitors. 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 a 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 bacterial life cycle activators or inhibitors. 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 long

5, 10, 20, 50, 100 or 150 amino acid residues; 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 the sequence of the invention that is contained in the Sequence Listing. However, the differences are only such that the H. pylori polypeptide exhibits H. pylori biological activity, 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 encoding the 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 H. pylori polypeptide portion and a second polypeptide portion, e.g. the second polypeptide portion has an amino acid sequence that does not relate 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 being capable of eliciting an immune response that is specific for the 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 an 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 contiguous amino acid residues of the invention that are included 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 H. pylori encoded polypeptide exhibits H. pylori biological activity, e.g. the encoded H. pylori enzyme retains the biological activity of naturally occurring H. pylori.

In preferred embodiments, the encoded 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 other amino acid residues, preferably residues encoded by 5 'or 3' 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 an 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 an 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 an H. pylori polypeptide variant as described herein; vector-transfected host cell; and a method of generating a recombinant H. pylori polypeptide or H. pylori polypeptide variant; including beech cultivation, 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 the nucleotide sequence that hybridizes under stringent conditions to at least 8 consecutive nuclides of the sense or antisense sequence of the invention, which is contained in the Sequence Listing, or naturally occurring mutants thereof. In preferred embodiments, the probe or primer further comprises an attached labeling group. The labeling group may be e.g. a radioisotope, a fluorescent compound, an enzyme, and / or an enzyme cofactor. Preferably, the 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 are: 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. pylon polypeptides, particularly antisera to the active sites or binding domains of H. pylori polypeptides. The invention also includes fragments, preferably biologically active fragments. These and other polypeptides are also referred to herein as H. pylori polypeptide analogs or variants.

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

Further, the present invention includes H. pylori polypeptides characterized as set forth in Table 1, below, including: H. py / ori cell envelope proteins, H. pylori secretory proteins, and H. pylori cell proteins. Members of these groups were identified by BLAST homologous 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

ORF Name and Group nt SEQ. if SEQ. no. | A. CELL PACKAGING A.1 Internal membrane proteins 02ge11622 23494043 f1 6 3 76 hp5p15212 13095752 c3 36 25 98 06ep30223 20173437 f1 37 48 121 | A.2 External membrane proteins 05ee10816 14495437 f2 13 10 83 | A.2.1 Terminal phe residue 06ep11509 35954752 f2 1 16 89 06ep10615 14495437 f3 47 45 118 03ae10804 14495437 c2 38 35 108 05ae30220 917200 c3 172 37 110 04cp11202 23646885J2 26 7 80

05ep10815 16131925 c2 97 39 112 09cp61003 5860877 f2 23 55 128 09ae10512 48768 c3 67 18 91 09cp11003 5860877 f3 7 19 92 J hp6e12267 30478562 f3 33 28 101 06cp30603 34174212 c3 71 30 103 09cp10224 1962590 f3 31 52 125 l09cp61003 30478562 c3 106 54 127 111 ae80818 10553192 f2 16 56 129 11ee11408 10584582 c3 51 58 131 A.2.2 Terminal phe residue and Cterminal tyrosine cluster 01ae12001 116018 c2 40 1 74 06ap10609 116018 c3 50 42 115 06cp30603 4687507 f1 9 14 87 06cp30603 4687507 f1 7 43 116 05ee10816 36126938 f3 16 11 84 01cp20708 4960952 c1 43 71 144 A.3 Through homology 07ap80601 5083193 f3 8 17 90 11ap20714 4797137 f3 45 57 130 A.4 Other cellular envelope proteins 04ap12016 25501501 f1 1 5 78 04cp11202 20415937J2 25 6 79 I04ee11108 3906963 ph 7 8 81 29ep10720 25501501 c2 33 21 94 f B. SECRET PROTEINS hp3e10342 22448587 c2 15 72 145 hp5p15212J24276587J1 2 32 105 09ce10413 35336707 f2 9 51 124 01ae12001 32462543 c2 43 2 75 03ee11215 1416312 c3 35 4 77 05ae30220 14570443 c2 94 9 82 06cp30603 2772578 c1 46 13 86 29ep10720 289077 f2 12 22 95 03ee11215 22542803J1 7 29 102 09ae10512 3166040 c1 40 31 104 01 ce11104 10742963 c2 12 33 106 02ge10116 36335436J3 66 34 107 04ep41903 11876461 f1 4 36 109 05ce10208 23631292 f1 7 38 111 05ep10815 22447252 c3 110 40 113 05ep10815 30283516 c3 109 41 114 06ee30709 33851038 c3 30 44 117 06ep11202 21687842 c3 35 46 119 06ep30223 2774062 f1 33 49 122 09cp10713 23912707 c1 26 53 126 11ee11408 4882318 f3 24 59 132 hp4e13394 5908553 f1 1 61 134 hp4e53394 1416312 c3 119 62 135 hp5e15211 24328910 c3 38 63 136

hp6p10606 23493756 c1 21 65 138 hp6p22217 23564012 f1 5 66 139 hp6p22217 272058 f1 2 67 140 hp6p22217 2922143 f2 9 68 141 C. OTHER CELL PROTECTORS 06ap11119 14726542 f3 21 12 85 06ee10709 6136430 c1 11 15 88 12ap10605 14094816 c1 5 20 93 hp2p10272 34042518J 1 2 23 96 hp5e15211 25411557 c1 23 24 97 hp5p15641 3907968 f1 3 26 99 hp6e10967 657638 f3 9 27 100 06ep11202 4569693 c2 28 47 120 06ep30223 3930468 c1 110 50 123 hp2e10911 960952 c2 86 60 133 hp6p10509 14642217 c2 16 64 137 hp6p80503 20964382 f2 11 69 142 hp7e10192 5917593 f1 2 70 143 hp6p10509 14642217 c3 25 73 14β |

In Table 1, nt means the nucleotide sequence identification number and if it represents 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, the 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 when chemically synthesized. Substantially free of cellular material includes H. pylori protein preparations in which the protein is separated from cellular components from cells from which it is isolated or recombinantly produced. In one embodiment, the substantially cell free expression includes H. pylori protein preparations having less than about 30% (dry weight) other than H. pylori protein (also referred to herein as contaminating protein), more preferably less than about 20% other than H. pylori protein, more preferably less than about 10% other than the H. pylori protein, and most preferably less than about 5% other than the 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.

Substantially free of chemical precursors or other chemicals includes H. pylori protein preparations 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 H. pylori protein having less than about 30% (dry weight) of chemical precursors or other than H. pylori chemicals, more preferably less than about 20% of chemical precursors or other chemicals more preferably less than about 10% of chemical precursors or other than H. pylori chemicals, and most preferably less than about 5% of chemical precursors or other than H. pylori chemicals.

Purified cell preparation means, in the case of plant or animal cells, an in vitro cell 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 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.

The coding sequence as used herein represents 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 nucleic acid complement, as used herein, means an antiparallel or antisense sequence that corresponds to a Watson-Crick base pairing of 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 a scavenger ligand. 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 nucleotide base pair composition and the temperature and salt concentration of 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 by: (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 solution of 0.5 x SSC, at 65 ° C) requires the sequences to be 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 polypeptides 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 H. pylori biological activity 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 a 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 that is 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 resulting from post-transcriptional processing or from 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 anaphor is one that exhibits biological activity in any H. pylori biological assay. activity. 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 manner that does not include the sequence, 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 sequence differs 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 H. pylori polypeptide. 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 I 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 1 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

For the amino acid code Replacement for any of lysine The D-Lys, Arg, D-Arg, homo-Arg, D-homo-Arg, Met, D-Met, Ile, D-Ile, Orn, D-Orn methionine M D-Met, S-Me-Cys, Ile, D-lle, Leu, D-Leu, 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 serine WITH D-Ser, D-Thr, D-Thr, D-Met, D-Met, O-D, Met-O, D-Met (O) 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 include, 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 a H. pylori analogue will generally be at least about 20 residues, 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 an 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 an 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 do so 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 the position of the natural gene or results in its deletion). 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 microinjection 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.

The term cell-specific promoter, as used herein, means a DNA sequence that serves as a promoter, that is, 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 the 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 refer to microorganisms or lines of higher eukaryotic cells cultured as unicellular entities, and means cells that may 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 so that they 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.

The metabolism of a substance as used herein means any aspect of the expression, function, activity or regulation of the 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 a nucleic acid from H. pylori and its use

H. pylori genomic sequence

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 # 55679; deposited with Genome Therapeutics Corporation, 100 Beaver Street, Waltham, 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 were ligated, and the fragments were cioned into each of 20 different pMPX vectors (Rice et al., Abstracts of Meeting of Genome Mapping and Sequencing, Cold Spring Harbor, NY). 11-5 / 15, 1994, p. 225) to construct a series of shotgun subclone libraries.

DNA sequencing was achieved using muitiplex 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 was chemically or enzymatically sequenced. 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 to a series of labeled oligonucleotides complementary to 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 the FAĽCON ™ program (Church et al., 1994, Automated DNA Sequencing and Analysis, JC Venter, eds., Academic Press) and PHRAP (P. Green, Abstracts of the DOE Human Genome Program Contractor- Grantee Workshop V, Jan. 1996, p.157). The average length of the contig was approximately 3-4 kb.

Different 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 template 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) containing at least 180 nucleotides. It should be understood that the result of an ORF analysis based on stop-stop codon readings may not correspond to the ORF of a 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 may be identified by one of ordinary skill in the relevant art, and the resulting ORF and encoded by 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 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).

According to the protocols described herein, it is also possible to obtain nucleic acids encoding H. pylori polypeptides 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.

U. U.S. Pat. 4,458,066; and Itakura U.S. Pat. U.S. Pat. No. 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, such 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 produce 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. It is found that a sequence of twenty or more nucleotides with the sequence information provided in the present application provides the desired inclusiveness and exclusivity with respect to H. pylori, and the likelihood of encountering external nucleic acids during 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 homologous regions (particularly homologous genes) of other

Helicobacter strains using suitable stringent hybridization conditions as described herein.

Capture ligand

For use as a scavenger ligand, the nucleic acid can be selected as described above for probes, commonly associated with a 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 that 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 that 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 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 primers to amplify H. pylori 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 that is included 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, nucleic acids or derivatives corresponding to H. pylori nucleic acids are loaded into a suitable carrier such as a liosome 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 can 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 the conditions in which the activity of the gene product (s) determined by the gene or operative 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 strains. 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 using 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 which, after treatment of the PCR product with a restriction enzyme or exonuclease, to ligate into the expression plasmid.

A suitable host cell for expression of the gene may be any prokaryotic or eukaryotic cell. For example, H. pylori polypeptide can 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 formation of relevant inter- or intra-chain disulfide bonds in the recombinant peptide product. Examples of vectors for expression in yeast S. cerivisae 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) Vimlogy 170: 3139). 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 (dhfr Chinese Hamster Ovary) cells 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 calcium phosphate or calcium chloride coprecipitation, DEAE-dextran mediated transfection or electroporation. Suitable methods for transforming host cells can be found in Samrook et al. al. (Molecular Cloninq: A Laboratory Manual, Second Edition, Cold Spring Harbor Laboratory Press (1989)), and other laboratory textbooks.

Expression in prokaryotes is most commonly performed in E. coli with either fused or unfused inducible expression vectors. Fused vectors usually add a number of NH2 terminal amino acids to the expressed target gene. These NH ₂ terminal amino acids are often referred to as the reporter group. Typically, such reporter groups serve two purposes: 1) increasing 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 proteolytic 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., Ene 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 trp1ac 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 there bearing Ί7 gnl under transcriptional control of the lacUV 5 promoter.

For example, a host cell transfected with a nucleic acid vector that is intended to express a nucleic acid sequence encoding an H. pylori polypeptide can be cultured under appropriate conditions that allow expression of the polypeptide to be performed. 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 may be isolated from cell culture medium, host cells, or both, using art-known protein purification techniques, including ion exchange chromatography, goal filter chromatography, ultrafiltration, electrophoresis, and immunoaffinity purification with antibodies specific for such. polypeptides. In addition, in many situations, the polypeptides can be produced by chemical cleavage of the native protein (e.g., triptic cleavage), and the cleavage products can then be purified by standard techniques.

In the case of membrane-bound proteins, they can be isolated from the host cell by contacting a fraction of the membrane-associated protein and the detergent to form a solubilized complex wherein 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 that is considered is the ability of a detergent to dissolve H. pylori protein within the membrane fraction with minimal denaturation of the membrane associated protein so as to allow the return or activity of the membrane associated protein upon reconstitution of the protein. another feature that is taken into account in the choice of detergent is the critical micelle 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. tifton 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 Enzvmoloq 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 for 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. 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 invention encompasses isolated H. pylori polypeptides encoded by the claimed H. pylori genomic sequences, including polypeptides of the invention, which 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 the template; followed by sequencing the amplified product.

Polypeptides of the invention may be isolated from 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 H has been expressed. 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.

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

The claimed H. pylori genomic sequence includes segments that direct the synthesis of ribonucleic acids and polypeptides, as well as origins of replication, promoters, other types of regulatory sequences, and intergenic 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 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 only a fraction of the entire protein coding sequence. identifying such traits in H. pylori sequences 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 importance to the organism by examining the effect of gene deletion and / or 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 because of 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 new 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 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

The selection of candidate protein antigens for vaccine development may be derived from nucleic acids encoding H. pylori plasmids. 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 D e Lisi, C. (1985) Biochimica et Biophysica Acta 815,468-476) for predicting exported and membrane proteins.

The homology search 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 ORF amino acid sequence to all sequences found in the current GenBank. , SWISS-PROT and PIR databases. 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 randomly 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 H. pylori genes.

Discriminant analysis (Klein, et al. Supra) can be used to examine ORF amino acid sequences. 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) that are in clusters, alternating at the C-terminus (e.g., see Figure 5, block F; 7, block E). Importantly, these sequences were not detected at the C-terminus of the periplasmic proteins, so that they make it possible 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 5 are additional amino acid sequence motifs found in many of the outer membrane proteins of H. pylori. The amino acid sequence alignment in Figure 5 depicts portions of the 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. Five or six separate blocks (labeled A to E or F) with similar amino acid residues have been found that contain symptomatic hydrophobic residues (Phe or Tyr; F or Y in a single letter amino acid residue code) that often occur at positions near the C-termini outer membrane proteins. The presence of several common motifs clearly demonstrates the similarity between members of this family of proteins.

Additional amino acid groupings of the four outer membrane proteins isolated from H. pylori are shown in Figure 6.

The outer membrane proteins isolated from H. pylori often share additional motifs as shown for the two proteins in Figure 7, which also have common C-terminal motifs of hydrophobic residues, and as depicted for the two proteins in Figure 8, which do not share C-terminal motifs hydrophobic residues but share another C-terminal motif.

One of skill in the art would know that these shared sequence motifs are very important in determining the similarity between this family of proteins.

Rarely, it is not possible to distinguish between different possible nucleotides at a given position in a nucleotide sequence. In such cases, ambiguity is indicated by the extended alphabet set out below:

Official IUPAC-IUB single letter base codes are listed.

Code_ Description of base_

G Guanín

And Adenin

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 binary codon is referred to as the letter "X." in amino acid translations of the invention that include binary nucleic acids. In all cases, possible amino acid residues at a particular position are apparent from the 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. recombinant, proteolytic cleavage, or 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 series 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 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 a Mn ² * to 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 cationized 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) Degenerated 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) Tetrahedron 39: 3; Itakura et al. (1981) Recombinant DNA, Proc 3rd Cleveland Sympos. Macromolecules, ed. AG Walton, Amsterdam: Elsevier pp273- 289; 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. 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 (Cwirla 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 replaced by a neutral or negatively charged amino acid (most preferably alenine 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 per mutation need 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 a 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 an oligonucleotide encoding a mutation to a DNA template, wherein the template is a single-stranded form of a plasmid or bacteriophage that contains an unaltered or natural DNA sequence of the protein of interest. After 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 stemplate on each side of the nucleotide (dov) that encodes the mutation. This ensures that the oligonucleotide will properly hybridize to the single stranded DNA template molecule. Oligonucleotides are commonly synthesized using techniques known in the art, such as described by Crea et al. (Prac. Natl. Acad. Sci. USA, 75: 5765 (1978)).

(C) Cassette mutagenesis

Another method for preparing variants, cassette mutagenesis, is based on the technique described by Wells 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, and the codon (s) of the DNA of the protein subunit to be mutated is identified. 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. A double-stranded oligonucleotide that encodes a DNA sequence between the restriction sites but containing the desired mutation (s) is synthesized using standard procedures, the two strands are synthesized separately and then hybridized together using standard techniques. The 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 the 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 containing a set of degenerate sequences.

Other modifications of H. pylori nucleic acids and polypeptides

It is possible to modify H. pylori polypeptide structures for purposes such as increasing solubility, enhancing 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 formed in which an amino acid sequence has been altered, for example, by amino acid substitution, deletion, or addition.

The H. pylori peptide may also be modified by substitution of cysteine residues, preferably 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 may 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 may be modified using polyethylene glycol (PEG) according to Method A.

Sehon et al. (Wie et al., Supra) to make 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 an appropriate carrier (Mishell and Shiigi, eds., Selected Methods in Cellular Immunology, WH Freeman, San Francisco, CA (1980), US Patent 4,939,239; or gentle formalin treatment (Marsh, (1971) Int. 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 placed between the fusion sequence and the peptide.

In order 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 susceptible 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 where detection of the desired activity, e.g. in this case, binding of the H. pylori polypeptide or interacting protein 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 the 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. cellular proteins or randomly generated polypeptides that bind the H. pylori protein. (The H. pylori domain is used as the bait protein and the variant library is expressed as captured fusion proteins). In an analogous manner, a 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) Bio / Technology 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 cells to be examined visually and separated under a fluorescent microscope or, if the cell morphology 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 ^-3 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 particular phage is obtained from a low yield affinity matrix, it may 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 protein can be used to generate fusion proteins without disrupting the necessary packaging of the viral particle. Foreign epitopes can be expressed on NH _{from the} p1 end 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: 725734 Clackson et al (1991) Nature 352: 624-628 and Barbas et al. (1992) PNAS 89: 4457-4461.

Conventional approaches use the maltose receptor as a partner for peptide fusion

E. coli (outer membrane protein, LamB) (Charbit et al. (1986) EMBO 5, 30293037). Oligonucleotides were inserted 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 9i, 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, the p13 provides a useful carrier for presenting peptides to the extracellular environment. Another large surface structure used for peptide display is the 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 Staphylococcus protein A and the outer membrane IgA Neisseria protease (Hansson et al. (1992) J. Bacteriol. 174, 42394245 and Klauser et al. (1990) EMBO J. 9,1991-1999).

In the filamentous phage systems and in the LamB 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 Lac1 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 Lac1-peptide fusion protein is produced by controlled induction of arabinose. This fusion 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 finely 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 was selected on a monoclonal antibody against the opioid peptide dynorphin B. A group of peptides were obtained, all related to containing a consensus sequence corresponding to the six residual portion of dynorphin B (Chuli et al. (1992) Proc. Natl. Acad. 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 pVIII, are anchored to the phage at their C-terminus, and the host proteins are positioned such that their N-terminal domains are 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 C-terminal hydrophobic domains, containing N-terminal peptides that protrude into the periplasm while waiting for assembly . 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 (Galiop et al. (1994) J. Med. Chem. 37 (9): 12331251). 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. In order to circumvent this limitation, an in vitro system based on exposure of nascent peptides to poysome complexes has recently 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 of this method (Gailop 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 manner as conventional recombinant peptide display libraries are searched. RNA from the bound complexes is removed, converted to cDNA, and amplified by PCR to provide 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 poysomes 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 polyzome-derived peptides on the 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 (Barret, 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 a reduction in 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 naturally-occurring ligand binding polypeptide. It is possible to determine 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 the binding of H. pylori polypeptide to the interacting polypeptide (see, e.g. 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) that mimic these residues when binding to an interacting polypeptide can be formed and can thus inhibit the 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, The 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-helical dipeptide nuclei (Nagai et al. (1985) Tetrahedron Flight 26: 647; and Sato et al. (1986) J Chem Soc Perkin Trans 1: 1231) , and β-aminoalcohols (Gordon et al. (1985) Biochem Biophys Res Commun126: 419; and Dann et al. (1986) Biochem Biophys Res Commun 134: 71).

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

The present invention also relates to vaccine compositions or preparations (used interchangeably herein to protect against H. pylori infection or to treat H. pylori infection. The term "treatment of H. pylori infection" as used herein means therapeutic treatment of an existing or established H. pylori infection. The terms "protection against H. pylori infection" or "preventive treatment" refer to the use of an H. pylori vaccine preparation to reduce the risk or prevent infection, in the case of a risk of H. pylori infection. In one embodiment, the vaccine compositions comprise one or more pylori infections. For example, in one embodiment the vaccine compositions of the invention comprise at least one or a combination of H. pylori polypeptides or fragments thereof from the same or different H. pylori antigens. Nucleic acids and H. pylori polypeptides for use in the vaccine compositions of the invention include nucleic acids and polypeptides of the Sequence Listing, preferably those of H. pylori nucleic acids that encode surface proteins or fragments thereof. For example, the preferred nucleic acid and H. pylori 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 listed in Table 1. However, any nucleic acid can be used in the present invention. an acid encoding an immunogenic H. pylori protein and H. pylori polypeptide, or a portion thereof. These vaccines have therapeutic and / or prophylactic uses.

One aspect of 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.

The immunogenic components of the invention can be obtained, for example, 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 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 the 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. H. pylori genome, may 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 can be incorporated at separate sites and can 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 with genes identified by genome sequencing can be used to immunize the host. The feasibility of this method has been demonstrated with Mycoplasma pulmonis (Barry 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 relevant MHC molecules, in a T cell culture. Presentation of the immunogenic H. pylori peptide associated with the respective MHC molecules to T cells, along with the necessary stimulation, causes signal transduction to the T cell, which induces increased production of cytokines, particularly 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 tritiated thymidine incorporation. 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 the 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 intended to include any and all solvents, dispersing media, coating agents, antibacterial and antifungal agents, isotonic and absorption delaying agents, and the like, which 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 adjuvants such as wetting or emulsifying agents, preservatives and timing solutions which increase the storage time and efficacy 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 the therapeutically effective amount of the DNA or protein of the invention will depend inter alia on the mode of administration, the dosage unit administered by H. pylori nucleic acid or polypeptide, 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. 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. For the induction of protection against H. pylori infection oral immunization is preferable to the parenteral methods of Czinn et. al. (1993) Vaccine H: 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-muramy 1-L-alany ID-isoglutamine (CGP 11637, referred to as nor-MDP); N-acetylmuramyl-L-alanyl-D-isoglutaminyl-L-alanine 4-O '- (dipalmitoyl-sn-glycero-5-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, derivatives muramyl dipeptide, phorbol esters, labile toxins of E. coli, ri \ eH. pylori bacterial lysates, block polymers or saponins.

In another embodiment, the vaccine composition comprises, as a pharmaceutically acceptable carrier, a delivery system. 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 of the invention, the vaccine composition comprises both a delivery system and an adjuvant.

The delivery system in humans can include enteric-release capsules that protect the antigen from the acidic environment of the stomach, and contain 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 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 an H. pylori γ 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 upon 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, preparation, 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 E. coli killed with an immunogenic fragment of H. pylori protein of the invention that is expressed on its surface, or may be based on 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. It is understood that 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 determine 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). Still another preferred embodiment of the invention, 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-reacting" 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

ΊΟ polypeptide and allow, by microinjection of anti- / 7. 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 H. pylori polypeptide in an individual may allow the efficacy of a given treatment regimen to be determined for an individual suffering from such a disorder. The level of H. pylori polypeptide may be measured in cells found in body fluid, such as urine samples, or may be measured in tissues obtained, for example, by gastric biopsy. Diagnostic tests using anti-H. 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-βylori 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 βgalactosidase amino acid sequences, and whose carboxy termini will consist of a foreign polypeptide. 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 anti-H plates. pylori polypeptide antibodies. Phages captured in this way can then be isolated from 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.

Vili. 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 comprise 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, for example, aqueous media, salts, buffers, and the like. The kits may also include sample processing agents such as detergents, chaotropic salts and the like. The kits may also include immobilizing agents such as particles, carriers, wells, scoops and the like. The kits may also include labeling means such as dyes, development agents, radioisotopes, fluorescent agents, luminescent or chemiluminescent agents, enzymes, intercalating agents, and the like. By utilizing the nucleic acid sequence information provided herein, one of skill in the art can readily assemble kits to serve a particular purpose. The kits may further comprise 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 suppression to suppress 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 are described to obtain the maximum number of compounds within a given time range. Methods that are performed in cell-free systems, which may be derived, for example, from 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 are mediated test compound. Moreover, in an in vitro system, the effects of cellular toxicity and / or bioavailability of a 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 may be constructed in vitro with purified H. pylori polypeptide or fragment thereof, such as H. pylori polypeptide having enzymatic activity, for example, the ability to generate 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 enhance the activity of the H. pylori polypeptide. 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.

Brief overview of the drawings

Figure 1 is a bar graph depicting the antibody titer in mouse serum after immunization with specific H. pylori antigens.

Figure 2 is a bar graph depicting the antibody titer in the mucosa of mice after immunization with specific H. pylori antigens.

Figure 3 is a bar graph depicting therapeutic immunization of H. pylori-infected mice with specific antigens dissolved in HEPES buffer.

Figure 4 is a bar graph depicting therapeutic immunization of H. pylori-infected mice with specific antigens dissolved in DOC-containing buffer.

Figure 5 shows the alignment of the amino acid sequence in a portion of the sequence of five H. pylori proteins (indicated by a single letter amino acid code; shown from N-terminal to C-terminal, left to right).

Figure 6 shows the amino acid sequence alignment in part of the sequence of four H. pylori proteins (indicated by a single letter amino acid code; shown from N-terminal to C-terminal, left to right).

Figure 7 shows the alignment of the amino acid sequence in a portion of the sequence of two H. pylori proteins (indicated by a single letter amino acid code; shown from N-terminus to C-terminus, left to right).

Figure 8 shows the alignment of the amino acid sequence in the portion of the sequence of two H. pylori tfe proteins indicated by the one letter amino acid code; shown from the N-terminus to the C-terminus, from left to right).

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. Kioning and sequencing of H. pylori DNA

H. pylori chromosomal DNA was isolated according to the basic DNA protocol of Schleif RF and Wensink PC, 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, 0.5% N-lauryl sarcosine)) was added. 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, the DNA 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 a mean 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 listed in Church G.M. and Kieffer-Higgins S., Science 240: 185-188, 1988. Only the major protocol modifications 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 transformatnes 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 generated to obtain a 5 to 10 fold sequence dilution 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 electrophoresed and transferred to nylon membranes by direct electrophoresis transfer from 40 cm gels (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. The DNA was covalently bound to membranes by being exposed to ultraviolet radiation, and the DNA hybridized to labeled oligonucleotides complementary to vector tag sequences (Church, supra). Membranes were washed to wash non-specific bound probes, and exposed to X-ray film to visualize individual sequential 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). Digitaized images were processed on computer workstations (VaxStation 4000's) using the REPLICA ™ program (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. Each sequence automatically received an identification number (corresponding to the microtiter plate, probe information, and kit number). 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., NudeicAcid 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 for rapid contig scanning and gel-scan readout when there is a discrepancy between different sequence records in the assembly.

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

To facilitate the cloning, expression and purification of membrane and secreted proteins from H. pylori, a strong pET gene expression system (Novagen) was selected for cloning and expression of recombinant proteins in E. coli. To facilitate the purification of recombinant protein products, it was also used

3 'end of the DNA target sequence fused DNA sequence encoding a peptide tag, His-tag. 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 J99 strain Helicobacter pylori

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 (ORF) 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 protein translation initiation 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. py / ori 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 6 histidine residues (at the complete C-terminus) that form a 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 the BamHI site at its full 5' end, and the primer for the 3 'end of the ppiB gene encoded the XhoI site at its full 5' end.

Table 3

The oligonucleotide primers used for PCR amplification of the H. pylori DNA sequence

External membrane proteins Direct primer 5 'to 3' Reverse Primer 5 'to 3' Protein 16225006 5'-TATACCATGGTGGG CGCTAA-3 '(Seq. £: 147) 5'-ATGAATTCGAGTAAG GATTTTTG-3 '(Seq. £. 148) Protein 26054702 5'-TTAACCATGGTGAAA AGCGATA-3 '(Seq. £: 149) 5-TAGAATTCGCATAAC GATCAATC-3 '(Seq. £. 150) Protein 7116626 S'-ATATCCATGGTGAGT TTGATGA-3 '(Seq. £: 151) 5'-ATGAATTCAATTTT I TATTTTGCCA-3 '(Seq.: 152) Protein 29479681 5'-AATTCCATGGTGGGG GCTATG-3 '(Seq.:153) 5'-ATGAATTCTCGATAG CCAAAÄTC-3 '(Seq. £. 154) Protein 14640637 S'-AATTCCATGGTGCAT AACTTCCATT-3 '(Seq. £. 155) 5'-AAGAATTCTCTAGCA TCCAAATGGA-3 '(Seq. £: 156) Periplasmic / Secreted Proteins Protein 30100332 5'-ATTTCCATGGTCATG TCTCATATT-3 '(Seq. £: 157) 5'-ÄTGAATTCCÄTCTTT TATTCCAC-3 '(Seq. £. 158) | Protein 4721061 5'-AACCATGGTGATTT TAAGCATTGAAAG-3 '(Seq. £: 159) 5 'AAGAATTCCACTCA AAATTTTTTAACAG-3 ' (Seq. £.: 160) Other surface proteins Protein 4821082 5'-GATCATCCATATGTT ATCTTCTAAT-3 '(Seq. £. 161) 5'-TGAATTCAACCATTT TAACCCTG-3 '(Seq. £. 162) Protein 978477 5-TATACCATGGTGAA Al 1111 ICTTTTA-3 '(Seq. £: 163) 5'-AGAATTCAATTGCG TCTTGTAAAAG-3 '(Seq. £: 164) Internal membrane protein Protein 26380318 5-TATACCATGGTGAT GGACAAACTC-3 '(Seq. £: 165) 5'-ATGAATTCCCACTT GGGGCGATA-3 '(Seq. £: 166) Cytoplasmic protein PPi 5'-TTATGGATCCAAAC CAATTAAAACT-3 '(Seq. £: 167) 5-TATCTCGAGTTATA GAGAAGGGC-3 '(Seq. £: 168)

Genomic DNA prepared from J99 H. pylori strain (ATCC # 55679; deposited with Genome Therapeutics Corporation, 100 Beaver Street, Waltham, MA 02154) was used as template DNA source for PCR amplification reactions (Current Protocols in Molecular Biology, 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 MgCl 2> 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 amplified DNA products, for each ORF the Perkin Elmer Cetus / GeneAmp PCR System 9600 thermal cycling was used:

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 and 72 ° C -1.5 min 23 cycles at 94 ° C -15 sec, 55 ° C -15 sec and 72 ° C -1.5 min The reaction was complete 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 and 72 ° C -1.5 min cycles at 94 ° C -15 sec, 60 ° C -15 sec and 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 and 72 ° C -1.5 min cycles at 94 ° C -15 sec, 62 ° C -15 sec and 72 ° C -1.5 min

Reactions were terminated at 72 ° C for 6 minutes.

Protein 14640637;

Denaturation at 94 ° C - 2 min, cycles at 94 ° C -15 sec, 33 ° C -15 sec and 72 ° C -1.5 min cycles at 94 ° C -15 sec, 55 ° C -15 sec and 72 ° C -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 sec, 32 ° C -15 sec and 72 ° C -1.5 min cycles at 94 ° C -15 sec, 56 ° C -15 sec and 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, USA), or in the case of HpSeq. 4821082 (SEQ ID NO: 1309), with Ndel and EcoRI (Current Protocols in Moiecular Biology, John Wiley & Sons, Inc.,

F. Ausubel et al., Eds., 1994). DNA samples were subjected to agarose gel electrophoresis on a 1.0% NuSeive (FMC BioProducts, Rockland, ME USA). The DNA was visualized by exposure to ethidium bromide and high wavelength UV radiation. The DNA contained in the isolated zagarose gel bands was purified using the Bio 101 GeneClean Kit protocol (Bio 101 Vista, CA, USA).

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

After digestion, the DNA inserts were cloned (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 insert in ppiB, 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, E. coli strain BL21 or E. coli strain BL21 (DE3), were transformed by recombinant pET expression plasmids carrying the cloned H. pylori sequences (Current Protocols in Molecular, John Wiley and Sons, Inc., F. Ausubel et al.) By standard methods. (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. Samples were then plated on LB agar plates containing 25 micrograms / m 2 (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

Individual 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 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 ORF were harvested and incubated in 5 ml LB medium with 25 micrograms / ml kanamycin suifate 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. pytora 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, for cloning or plasmid preparation. Expression hosts include E. coli strains containing a chromosomain 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 H. pylori recombinant 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 kanamicin sulfate. On the following day, bacterial colonies were harvested and grown in LB medium containing kanamicin sulfate (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 H. pylori recombinant DNA constructs.

After induction of gene expression with IPTG, the bacteria were settled by centrifugation in

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). The cells were then centrifuged at 2000 x g for 20 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 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% giycerol, 0.1% 2-mercaptoethanol, 200 mg / ml lysozyme, 1 mM phenylmethylsulfonyl fluoride (PMSF) ), and 10 pg / 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 microfludizer (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 supor filter (Gelman Sciences, FRG), the crude extract was applied directly to Ni 5+ 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 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 subsequent steps, lysis buffer containing 10% glycerol, 0.05% Brij 35, 1 mM PMSF, and successively 20, 100, 200, and 500 mM imidazole. Fractions were monitored by absorbance at OD 280 nm, ^θ peak fractions were analyzed by SDS-PAGE. Fractions containing the recombinant protein were eluted at 100 mM imidazole.

Recombinant 14640637 and β-galactosidase (lacZ) and peptidyl-prolyl cis-trans isomerase (ppiB) proteins

Fractions containing recombinant proteins from Ni ²⁺ -NTA-agarose columns were collected and concentrated to approximately 5 ml by centrifugal 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 the recombinant protein from a Ni ²⁺ -NTA-agarose column were collected and dialyzed overnight against 1 liter of diaysis 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 Biotechnoogy, Inc., Piscataway, NJ, USA) equilibrated in B buffer (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 the cell disrupter, the resulting homogenate was mixed with 0.2% deoxycholate 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 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 clear supernatant was filtered, and then loaded onto an Np ⁺ -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 280 nm, and peak fractions were analyzed for

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 Buffer B, 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 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; 6M, 4M, 3M, 2M, 1M, 0.5M 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), Bradfo.d ((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.

Table 4

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

External membrane proteins

16225006 P28635 YEAC inclusion bodies His-tag 18 kDa 5 mg / ml B 26054702 P15929 flgH inclusion bodies His-tag 37 kDa 1.18 mg / ml B dry pellets 7116626 P26093 e (P4) soluble faction His-tag 29 kDa 0.8 mg / ml A 1.85 mg / ml C 29479681 P13036 fecA inclusion bodies SP- Sepharose 23 kDa 2.36 mg / ml B 0.5 mg ml B - as dry pellets 14640637 P16665 TPF1 soluble faction His-tag 17 kDa 2.4 mg / ml A gel filtration S100 HR I

Periplasmic / secreted proteins

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 I

Other surface proteins

| W821082 P08089 M protein inclusion bodies His-tag 20 kDa 1.16 mg / ml B 978477 L28919 FBP54 inclusion bodies SP- Sepharose 44 kDa 2.56 mg / ml B I 0.3 mg / ml B

Internal membrane proteins

26380318 P15933 Fligel inclusion bodies SP- Sepharose 11 kDa 22 mg / ml B IJ99 jldentifik. isekvencie homologue caller ID. protředí. BLAST genic symbol homologue 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 Control Prinines with His- Pendant P00722 lacZ soluble faction His-tag 116 kDa 10 mg / ml A gel filtration S200 HR | ppiB soluble faction His-tag 21 kDa 4.4 mg / ml A gel filtration S100 HR 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 I

IV. Analysis of H. pylori proteins as vaccine candidates

A mouse was used to investigate the immunomodulatory effect of H. pylori proteins. pylori model. This model mimics human H. pylori infection in many respects. Emphasis is placed on the effect of oral immunization in H. pylori-infected animals to test the concept of therapeutic oral immunotherapy.

The animals

Female SPF BALB / c mice were purchased from the Bomholt Breeding Center (Denmark). They were kept in conventional macrocolumn cages with free access to water and food. On arrival, the animals were 4 to 6 weeks old.

infection

After at least one week of acclimatization, animals were infected with a type 2 (VacA negative) strain of H. pylori (strain 244, originally isolated from a patient with ulcers). We have previously verified that this strain is a good colonizer of the mouse stomach. The bacteria were grown overnight in Brucella medium supplemented with 10% fetal bovine serum at 37 ° C in a microaerophilic atmosphere (10% CO 2, 5% O 2).

The animals were given an oral dose of omeprazole (400 pmol / kg) and 3-5 hours later, they were orally inoculated with H. pylori in the medium (approximately 10 cfu / animal). In some animals a positive uptake of infection was detected 2 to 3 weeks after inoculation.

antigens

Recombinant H. pylori antigens were selected based on their association with an externally exposed H. pylori cell membrane. These antigens were selected from the following groups: (1) outer membrane proteins; (2.) Periplastic / Secretory proteins; (3) external surface proteins; and (4) intrinsic membrane proteins. All recombinant proteins were constructed with a hexa-HIS tag for purification purposes and the non-Helicobacterpylori control protein (β-galactosidase from E. coli; LacZ) was constructed in the same way.

All antigens were administered in soluble form, i.e. dissolved either in HEPES buffer or in buffer containing 0.5% Deoxycholate (DOC).

Antigens are listed in Table 5 below.

Table 5

Helicobacter pylori proteins

External membrane proteins

Protein 7116626

Protein 4721061

Protein 16225006

Protein 29479681

Protein 14640637

Periphasic / secretory proteins

Protein 30100332

Other cellular envelope proteins

Protein 4821082

Flagellate-associated proteins

Protein 26380318

Control proteins β-galactosidase (LacZ)

immunizations

Of each group, 10 animals were immunized 4 times over a 34 day period (days 1, 15, 25 and 35). Purified antigens were administered in solution or suspension at a dose of 100 mg / mouse. As an adjuvant, animals were given 10 µg / mouse cholera toxin (CT) with each immunization. The animals were administered orally, 3 to 5 hours before immunization, with omeprazole (400 mmol / kg) to protect the antigen from acid degradation. Infected control animals received HEPES buffer + CT or DOC buffer + CT. The animals were sacrificed 2 to 4 weeks after the final immunization. A general overview of the test is given in Table 6 below.

Table 6

Therapeutic immunization test overview:

All mice were infected with H. pylori strain Ah244 on day 30.

substance Mouse strain n = 10 Dose / mouse Batch dates 1. Controls, PBS Balb / c 0.3 ml 0.14, 24, 34 2. Cholera toxin, 10 pg Balb / c 0.3 ml 0, 14, 24, 34 3. Protein 16225006, 100 pg + CT 10 pg Balb / c 0.3 ml 0, 14, 24, 34 4. Protein 26054702 100 pg + CT 10 pg Balb / c 0.3 ml 0, 14, 24, 34 5. Protein 26380318 100 pg + CT 10 pg Balb / c 0.3 ml 0, 14, 24, 34 6. Protein 29479681 100 pg + CT 10 pg Balb / c 0.3 ml 0, 14, 24, 34

7. Protein 30100332, 100 pg + CT 10 pg Balb / c 0.3 ml 0.14, 24, 34 8. Protein 4721061, 100 pg + CT 10 pg Balb / c 0.3 ml 0, 14, 24, 34 9. Protein 4821082,100 pg + CT 10 pg Balb / c 0.3 ml 0, 14, 24, 34 10. Protefn 7116626,100 pg + CT 10 pg Balb / c 0.3 ml 0, 14, 24. 34 11. Protein 14640637,100 pg + CT 10 pg Balb / c 0.3 ml 0, 14, 24. 34

Analysis of infection

Mucosal infection: Mice were sacrificed using CO 2 and cervical dislocation. The abdomen was opened and the stomach was removed. After cutting up the stomach along the larger curvature, it was rinsed with saline. Surgical scalpel was 2 scraped separately zantra and 25mm stomach body. The scraped mucosa was suspended in Brucella medium and plated on Blood Skirrow selection plates. Plates were incubated under microaerophilic conditions for 3-5 days and the number of colonies was counted. The identity of H. pylori was verified by urease and catalase assays and by direct microscopy or Gram staining.

The urease test was performed essentially as follows. The urea agar base concentrate reagent was purchased from DIFCO Laboratories, Detroit, M1 (Catalog # 0284-61-3). The urea agar base concentrate was diluted 1:10 with water. 1 ml of undiluted concentrate was mixed with 100 to 200 ml of actively growing H. pylori cells. The color change to fucsin indicated that the cells were urease positive.

The catalase assay was performed essentially as follows. The reagent N.N.N'.N'-tetramethyl-p-phenylenediamine was purchased from Sigma, St. St. Louis, MO (Catalog # T3134). A reagent solution (1% w / v in water) was prepared. H. pylori cells were aspirated onto Whatman filter paper and overlaid with 1% solution. The change in color to dark blue indicated that the cells were catalase positive.

Serum Antibodies: They were prepared from the serum of all mice, from blood drawn by heart puncture. Serum antibodies were identified by conventional ELISA techniques in which specific Helicobacter pylori antigens were applied.

Mucosal Antibodies: 50% of the mice gently scraped the confined parts of the stomach body and the 4 cm duodenum to detect the presence of antibodies in the mucosa. The antibody titer was determined by conventional ELISA techniques as for serum antibodies.

Statistical analysis: The Wilcoxon-Mann-Whitney sign rank test was used to determine the significant effects of antigens on Helicobacter pylori colonization. P <0.05 was considered significant. Since antrum is a major colonization site for Helicobacter, the greatest emphasis was placed on changes in anthra colonization.

The results

Serum Antibodies: All tested antigens administered with CT produced a measurable specific titer in serum. The highest responses were observed for protein 7116626, protein 4721061, protein 26380318, protein 14640637 and protein 4821082 (see Figure 1).

Mucus Antibodies: Specific antibodies against all tested antigens were observed in scraped mucus. By far the strongest response was observed for protein 30100332, followed by protein 14640637, and protein 26380318 (see Figure 2).

Effects of therapeutic immunization

All control animals (BALB / c mice) were colonized with H. pylori (strain AH244) in both the womb and stomach body. Of the antigens tested, 3 proteins (protein 4721061, protein 4821082, and protein 14640637) showed a good and significant reduction and / or eradication of H. pylori infection. The degree of anthra colonization was lower than that of the control after immunization with 7116626 and 26380318. The effect of 16225006, 29479681, and 30100332 was not different from the control. The lacZ control protein, i.e., non-H. pylori protein, showed no eradication effect, and in fact had higher Helicobacter colonization compared to the HEPES + CT control. All data are shown in Figure 3, for proteins dissolved in HEPES, and in Figure 4, for proteins dissolved in DOC. Data are shown as geometric mean values. n = 8-10 Wilcoxon93

Mann-Whitney sign rank test * = p <0.05; x / 10 = number of mice showing H. pylori fracture eradication total number of mice examined.

The data presented suggests that all H. pylori associated proteins included in this study, when used as oral immunogens in conjunction with oral CT adjuvant, result in stimulation of the immune response as measured by specific serum and mucosal antibodies. Most proteins resulted in a reduction, and in some cases, complete disappearance of H. pylori colonization in this animal model. It should be noted that the reduction or disappearance was due to heterologous protection rather than homologous protection (the polypeptides were based on the H. pylori J99 strain sequence and were used for therapeutic immunization studies against a different (AH244) inducing strain, indicating the vaccine potential against a broad range of H. pylori strains).

The greatest anthra colonization was observed in non-Helicobacter LacZ treated animals, indicating that the effects observed with Helicobacter pylori antigens were specific.

The summary of these data strongly supports the use of these H. pylori proteins in pharmaceutical preparations for human use, for the treatment and / or prevention of H. pylori infections.

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 H. pylori strain J99, and other H. pylori strains isolated from human patients.

Preparation of chromosomal DNA

Cultures of H. pylori strains (listed in Table 9) were grown in BLBB (1% Trypton, 1% peptamine 0.1% glucose, 0.2% yeast extract 0.5% sodium chloride, 5% fetal bovine serum) to 0, The 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 Tris94.

HCl, 0.1 mM EDTA (TE). Lysozyme was added to a final concentration of 1mg / ml along with SDS to 1% and RNAase A + T1 to 0.5mg / 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 was incubated at 55 ° C for more than one hour. NaCl was added to the sample at a concentration of 0.65 M, mixed gently, and 0.15 ml of 10% CTAB in 0.7M NaCl (final 1% CTAB / 70mM NaCl) was added, followed by incubation at 65 ° C for 20 minutes. At this point, the samples were extracted with chloroform: isoamyl alcohol, extracted with phenol, and extracted again with chloroform isoamyl alcohol. DNA was precipitated with either EtOH (1.5 x volume) or isopropanol (0.6 x 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 a template DNA source for the PCR amplification reaction. To amplify a DNA sequence containing 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 7) complementary to the edges of H. pylori ORF, 0. 2 mM 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 7

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

J Outer membrane I proteins direct primer 5 'to 3' 5 'to 3' reverse primer Protein 26054702 (for strains AH4, AH 15, AH6I, 5294.5640, AH 18, and AH244) 5 TTAACCATGGTGAAAAGC GATA-3 '(SEQ ID NO: 169) 5'- TAGAATTCGCCTCTAAAA CTTTAG-3 '(SEQ ID NO: 170) Protein 26054702 (for strains AH5,5155,7958, AH24, aJ99) 5'- TTAACCATGGTGAAAAGC GATA-3 '(SEQ ID NO: 171) 5'- TAGAATTCGCATAACGAT CAATC-3 '(SEQ ID NO: 172)

External membrane proteins direct primer 5 * to 3 * reverse primer 5 'to 3' Protein 7116626 5'- ATATCCATGGTGAGTTTG ATGA-3 '(SEQ ID NO: 173) 5'- ATGAATTCAATTTTTTATT TTGCCA-3 '(SEQ ID NO: 174) Protein 29479681 5'- AATTCCATGGCTATCCAA ATCCG-3 '(SEQ ID NO: 175) 5'- ATGAATTCGCCAAAATCG TAGTATT-3 '(SEQ ID NO: 176) Protein 346 5'- GATACCATGGAATTTATG AAAAAG-3 '(SEQ ID NO: 177) 5'- TGAATTCGAAAAAGTGTA GTTATAC-3 '(SEQ ID NO: 178)

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 and 72 ° C -1.5 min cycles at 94 ° C -15 sec, 55 ° C at 15 sec and 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 - 2 min, cycles at 94 ° C -15 sec, 30 ° C -15 sec and 72 ° C -1.5 min 25 cycles at 94 ° C -15 sec, 55 ° C -15 sec and 72 ° C -1.5 min The reaction was complete at 72 ° C - 6 min.

Protein 26054702 and protein 294796813 - strains AH4, AH15, AH61, 5294, 5640, AH18, and Hp244;

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

Reactions were completed at 72 ° C for 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.

Cloning of H. pylori DNA sequences into a 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 TOP10F '(INVaF' for H. pylori sequence 350) E. coli strain as described below.

Transformation of competent cells by recombinant plasmids

Competent bacteria, the E. coli strain TOP10F 'or the 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 Wiiey and Sons, Inc., F. Ausubel et al. 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 were admixed to competent cells and incubated on ice for 30 minutes. The cells and ligation mixture were then subjected to heat shock at 42 ° C for 30 seconds, and then placed on ice for an additional 2 minutes, after which the samples were incubated in 0.45 ml SOC medium (0.5% yeast extract, 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 to evaluate the 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 ORF 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 cation vector (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 the ABI Sequencer using standard protocols (Perkin Elmer), using the vector-specific primers (found in PCRII or pCR2.1, Invitrogen, San Diego, CA), and the ORF-specific sequencing primers listed in Table 8 , below.

Table 8

Oligonucleotide primers used for sequencing H. pylori DNA sequences

External membrane proteins 5 'to 3' straight primers Reverse Primers 5 'to 3' Protein 26054702 5'- CCCTTCATTTTAGAAATCG3 ’(SEQ ID NO: 179) 5'- ATTTCAACCAATTCAATGC G-3 '(SEQ ID NO: 180) 5'- GCCCCTTTTGATTTGAAGC T-3 ’(SEQ ID NO: 181) 5'- TCGCTCCAAGATACCAAGA AGT-3 ’(SEQ ID NO: 182) 5'- CTTGAATTAGGGGCAAAGA TCG-3 ’(SEQ ID NO: 183) 5'- ATGCGTTTTTACCCAAAGA AGT-3 '(SEQ ID NO: 184) 5'- ATAACGCCACTTCCTTATT GGT-3 ’(SEQ ID NO: 185) 5'- CTTTGGGTAAAAACGCATC3 ’(SEQ ID NO: 186) 5'- CGATCTTTGATCCTAATTC A-3 '(SEQ ID NO: 187) 5'- ATCAAGTTGCCTATGCTGA3 ’(SEQ ID NO: 188)

| External 1 membrane proteins Straight 5 * to 3 'primers Reverse Primers 5 'to 3'

Protein 7116626 5'- TTGAACACTTTTGATTATG CGG-3 '(SEQ ID NO: 189) 5'- GGATTATGCGATTGTTTTA CAAG-3 '(SEQ ID NO: 190) 5'- GTCTTTAGCAAAAATGGCG TC-3 '(SEQ ID NO: 191) 5'- AATGAGCGTAAGAGAGCCT TC-3 · (SEQ ID NO: 192) protein 29479681 5'- CTTATGGGGGTATTGTCA-3 '(SEQ ID NO: 193) 5'- AGCATGTGGGTATCCAGC3 '(SEQ ID NO: 194) 5'- AGGTTGTTGCCTAAAGACT3 '(SEQ ID NO: 195) 5'-CTGCCTCCACCTTTGATC3' (SEQ ID NO: 196) Protein 346 5'- ACCAATATCAATTGGCACT3 '(SEQ ID NO: 197) 5'- ACTTGGAAAAGCTCTGCA3 '(SEQ ID NO: 198) 5'- (TgGCTTGTC ATATCTAGC3 '(SEQ ID NO: 199) 5'- G T GA GAAGTGTTGGTGCTA-3 '(SEQ ID NO: 200) 5'- CAAGCAAGTGGTTTGGTTT TAG-3 '(SEQ ID NO: 201) 5'- TGGAAAGAGCAAATCATTG AAG-3 '(SEQ ID NO: 202) 5'- GCCCATAATCAAAAAGCCC AT-3 '(SEQ ID NO: 203) 5'- CTAAAACCAAACCACTTGC T TGTC-3 * (SEQ ID NO: 204) Vector primers 5'-GTAAAACGACGGCCAG-3 '(SEQ ID NO: 205) 5'-CAGGAAACAGCTATGAC3 '(SEQ ID NO: 206)

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 H. pylori strain J99, were sequenced for a total length of 897 nucleotides, 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 manner, 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 strains of Helicobacter pylori. 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 iron (III) 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 the DNA sequence and in the deduced protein sequence were compared to the DNA and deduced protein sequences found in the J99 strain of H. pylori (see Table 9 below). Results are reported as percent identity to the J99 strain of H. pylori sequenced by random shotgun cloning. To control for any deviations in the J99 sequence, each of the four open reading frames was cloned and sequenced again from the J99 bacterial strain, and this sequence information was compared to the sequence information that was obtained by zinc inserts randomly shotgun by sequencing the J99 strain. The data demonstrate that the DNA sequence excursion is in a small range of 0.12% difference (protein 346, J99 strain) 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).

100

Table 9

Multiple stem DNA sequence analysis of H. pylori vaccine candidates

J99 Protein #: 26054702 2054702 7116626 7116626 29479681 29479681 346,346

Length sequenced

areas: 248 ak. 746 nt. 232 ak. 96 nt. 182 ak. 548 nt. 273 ak. 819 nt. Test strain IF identity Nuk. identity IF identity Nuk. identity IF identity Nuk. identity IF identity Nuk. identity 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% 5640 95.16% 94.37% 97.41% 95.69% 99.09% 97.63% 98.53% 95.48% AHI8 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. = did not take place

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.

101

The procedure for deleting portions of H. pylori genes / ORFs and for insertional mutagenesis of a 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. Biologicai 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 H. pylori genomic sequence 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.

Genomic DNA prepared from the Helicobacter pylori HpJ99 strain (ATCC 55679; deposited with Genome Therapeutics Corporation, 100 Beaver Street, Waltham, 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., Editors, 1994). For the preparation of genomic DNA from H. pylori, see Example I. PCR amplification is performed by placing 10 nanograms of genomic HpJ99 DNA in a reaction tube containing 10 mM Tris pH 8.3, 50 mM KCl, 2 mM MgCl 2, 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 a final volume of 40 microliters. PCR is performed in a Perkin Elmer Cetus / GeneAmp PCR System 9600 thermal cycler.

After completion of the thermal cyclic reactions, each sample of amplified DNA is visualized on a 2% TAE agarose gel stained with ethidium bromide (Current

102

Protocols in Molecular Biology (John Wiley &amp; Sons, Inc., F. Ausubel et al., Eds., 1994), thereby verifying that the reaction results in one product of the expected size. The amplified DNA is then washed and purified using a Qiaquick Spin PCR purification kit (Qiagen, Gaithersburg, MD, USA).

PCR products were cloned into pT7Blue T-vector (Catalog # 69820-1, Novagen, Inc., Madison, WI, USA) using a TA cloning strategy (Current Protocols in Molecular Biology, John Wiley &amp; Sons, Inc., F. Ausubel et al. 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 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.

Ligation products were electroporated (Current Protocols in Molecular Biology, John Wiley &amp; Sons, Inc., F. Ausubel et al., Editors, 1994) into electroporally competent XL-1 Blue or DH5- and E. coli cells (Clontech Lab., Inc., Palo Alto, CA). Briefly, 1 microliter of the ligation reaction is mixed with 40 microliters of electrocompetent cells and subjected to a high voltage pulse (25 gF, 2.5 kV, 200 Ω), 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-colored 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 cloned inserts, using the same forward and reverse primers that were used to initially amplify the J99 H. pylori sequence. Confirming that they were cloned

103 correct inserts is the appearance of 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 harvested from these verified clones and used in subsequent cloning steps.

These gene / ORF sequences are reused to design a second pair of primers that flank the region of the H. pylori DNA to be either interrupted or deleted (up to 250 base pairs) within the ORF, but oriented away from each other. Stocks of circular plasmid DNA, 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 essentially in the 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.

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 Molecular 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 are repaired using the Klenow Fill Protocol, which comprises mixing 4 µg of DNA fragment, 1 microliter of dATP, dGTP, dCTP, dTTP at a concentration of 0.5 mM, 2 microliter 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 inactivating the enzyme by heating to 75 ° C for 10 min. This blunt-ended kanamycin cassette is then purified through Qiaquick

104 column (Qiagen, Gaithersburg, MD, USA) to eliminate nucleate. T-ends are then formed by mixing 5 micrograms of blunt-ended kanamycin cassette, 10 mM Tris pH 8.3, 50 mM KCl, 2 mM MgCl 2, 5 units of DNA polymerase (Amplitaq, Roche Molecular Systems, Inc., Branchburg, NJ, USA). ), 20 microliters of 5 mM dTTP, in 100 microliters of the 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 ligase 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- and E. coli cells by electroporation as described above. After restoration, in the SOC, the cells are paid for

LB plates containing 100 micrograms / ml ampicillin and grow 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 pT7Bfue vector and the newly introduced kanamycin resistance gene. 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).

To verify that kanamycin is incorporated into the H. pylori genes / ORF and to determine the orientation of the insertion of the kanamycin resistance gene relative to the H. pylori genes / ORF, several PCR amplification assays are performed on these plasmids. 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 originally used for cloning 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 prevent the potential polar effects of the kanamycin resistance cassette on H. pylori gene expression, the

The orientation of the kanamycin resistance gene relative to the knock-out gene / ORF and both orientations are eventually used in H. pylori transformations (see below). To determine the orientation of the insertion of the kanamycin resistance gene, primers are designed from the ends of the kanamycin resistance gene (Kan-1 5'ATCTTACCTATCACCTCAAAT-3 '(SEQ ID NO: 207)) and Kan-2 5'AGACAGCAACATCTTTGTGAA-3' (SEQ. .: 208)). The orientation of the kanamycin cassette relative to the H.pylori sequences is determined using each of the cloning primers in conjunction with each of the Kan primers (4 primer combinations). Positive clones are termed either A 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 strains of H. pylori are used for transformation: ATCC 55679, a clinical isolate that provided DNA to obtain the H. pylori sequence database, and AH244, an isolate that has been passaged and has the ability to colonize the mouse stomach. Cells for transformation were grown at 37 ° C, 10% CO 2, 100% humidity, either on sheep blood agar plates or in liquid Brucella medium. Cells grow into an exponential phase and are examined by microscope to see if they are "healthy (actively moving) and not 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 to 5 OD @ 00 units / 25 microliter) of the 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, the cells are treated

10 6 apply 10 microliters of plasmid DNA (100 micrograms per microliter). In parallel, a positive control (plasmid DNA with ribonuclease 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 phenol: chloroform (1: 1) 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 along 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. The positive result of homologous recombination at the correct site on the chromosome should be seen as a single PCR product, the size of which is equal to the size of 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),

107 whether plasmid DNA with an 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 incorrect 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 gene / ORF and not present in plasmid) and either with Kan-1 or Kan-2 primer, depending on whether plasmid DNA with A or B is used 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 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.

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.

In case 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 on DNA from the transformed population before 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 undergo homologous recombination at the correct chromosome site. If test 2 and test 3 are positive, then

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.

Villas. Highly effective drug search test

Protein cloning, expression and purification

Cloning, transformation, expression and purification of the H. pylori target gene and its protein product, e.g. The H. pylori enzyme to be used in the high throughput drug screening assay 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 gene product, peptidylpropyl cis-trans isomerase, 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-β-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 in the assay 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 (type 1-5 from bovine pancreas, Sigma # C-7762, lot 23H7020) and 10 nM PPIase. To initiate the reaction, 10 μΙ of substrate (2 mM N-succinyl-Ala-Ala-Pro-Phe-p-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 600 nm ~ 1) ^and suspended in the lysis buffer with the following protease inhibitors: 1 mM PMSF, and 10 pg / ml each of aprotinin, leupeptin, pepstatin, TLCK, TPCK, and soybean trypsin

109 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 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.

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.

110

LIST OF SEQUENCES

D General information:

(i) APPLICANT:

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

(E) COUNTRY: Sweden (F) MAIL POINT (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: 208 (iv) READERS FORM:

(A) MEDIA TYPE:

(B) COMPUTER:

(C) OPERATING SYSTEM:

(D) SOFTWARE:

(v) DATA 0 OF THE APPLICATION FORM:

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

(vi) PREVIOUS APPLICATION DETAILS:

(A) APPLICATION NUMBER: US 08 / 739,150 (B) SUBMISSION DATE: 28-OCT-1996 (vii, PREVIOUS APPLICATION DETAILS:

(A, APPLICATION NUMBER: US 08 / 759,739 (B, SUBMISSION DATE: 06-DEC-1996 (viii, PREVIOUS APPLICATION DATA):

APPLICATION NUMBER: US 08 / 891,928 (B, DATE OF SUBMISSION: 14-JULY-1997 (ix) CORRUPTION ADDRESS:

(A, ADDRESS: Astra Aktiebolag, Patents Department (B, STREET: S-151 85 (C) CITY: Sôdertälje (D, STATE:

(E, COUNTRY: Sweden (F, POSTAL GUIDANCE NUMBER:

(X, REPRESENTATIVE INFORMATION:

(A) NAME: Clube, Jasper (B) REGISTRATION NUMBER:

(C) BRAND: H 1818 (xi) TELECOMMUNICATIONS:

(A) PHONE: +46 8 553 260 20 (B) PHONE: +46 8 553 288 20 (2) INFORMATION ABOUT SEQ. NO.: L:

(i, SEQUENCE CHARACTERISTICS:

(A) LENGTH: 561 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D, TOPOLOGY: circular

111 (ii) MOLECULA 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 ... 561 (xi) SEQUENCE DESCRIPTION: SEQ. NO.: L:

ATGATTAAAA GAATTGCTTG TATTTTAAGC TTGAGCGCGA GTTTAGCGTT AGCTGGCGAA 60 GTGAATGGGT TTTTCATGGG TGCGGGTTAT CAACAAGGTC GTTATGGCCC TTATAACAGC 120 AATTACTCTG ATTGGCGTCA TGGCAATGAC CTTTATGGTT TGAATTTCAA ATTAGGTTTT 180 GTAGGCTTTG CCAATAAATG GTTTGGGGCT AGGGTGTATG GCTTTTTAGA TTGGTTTAAC 240 ACTTCAGGGA CTGAACACAC CAAAACCAAT TTGCTCACCT ATGGCGGCGG TGGCGATTTG 300 ATTGTCAATC TCATTCCTTT GGATAAATTC GCTCTAGGTC TCATTGGTGG CGTTCAATTA 360 GCCGGAAACA CTTGGATGTT CCCTTATGAT GTCAATCAAA CCAGATTCCA GTTCTTATGG 420 AATTTAGGCG GAAGAATGCG TGTTGGGGAT CGCAGTGCGT TTGAAGCGGG CGTGAAATTC 480 CCTATGGTTA ATCAGGGTAG CAAAGATGTA GGGCTTATCC GCTACTATTC TTGGTATGTG 540 GATTATGTCT TCACTTVCTA G 561 (2). NO. 2:

(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) SIGN: (A, NAME / KĽĎČ: different characters (B) PLACEMENT 1 ... 351

(xi, SEQUENCE DESCRIPTION: SEQ ID NO: 2:

TTGATGCGCA TTATCATAAG GTTACTTTCA TTTAAAATGA ACGCTTTTTT AAAACTCGCG 60 CTCGCTTCTT TGATGGGGGG GCTTTGGTAT GCTTTCAATG GCGAAGGCTC TGAGATTGTC 120 GCTATAGGGA TTTTTGTGTT GATCTTGTTT GTTTTTTTTA TCCGCCCTGT GAGTTTCCAA 180 GACCCAGAAA AACGAGAAGA ATACATAGAA CGGCTTAAAA AAAACCATGA GAGGAAAATG 240 ATCTTACAAG ACAAGCAAAA AGAAGAGCAA ATGCGCCTCT ATCAAGCCAA AAAAGAGCGA 300 GAGAGCAGGC AAAAACAAGA CCTTAAAGAA CAAATGAAAA AATACTCATA and 351 (2) INFORMATION ON SEQ. No ..- 3:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 1038 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular (ii) MOLECULAR TYPE: DNA (genomic)

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

(A) ORGANISM: Helicobacter pylori SIGN: (A) NAME / KEY: different characters (B) PLACEMENT 1 ... 1038

(xi) SEQUENCE DESCRIPTION: SEQ. No. 3:

ATGGTTAAAC ACTATCTTTT CATGGCGGTT TCGCAGGTCT TTTTCTCCTT CTTTTTAGTG CTGTTTTTTA TCTCTTCCAT TGTGTTATTA ATCAGTATTG CAAGCGTAAC GCTCGTGATT AAAGTGAGCT TTTTGGATCT GGTGCAACTC TTTTTGTATT CCTTGCCAGG AACCATTTTT TTTATTTTGC CGATCACTTT TTTTGCGGCT TGCGCTTTGG GGCTTTCAAG GCTTAGCTAT GACCATGAAT TGTTAGTGTT TTTCTCTTTA GGGGTTTCGC CTAAAAAAAT GACTAAAGCG TTTGTGCCTT TAAGTTTGTT AGTGAGCGCG ATTTTATTAG CGTTTTCGCT CATCTTAATC CCCACTTCTA AGAGCGCTTA TTACGGGTTT TTGCGTC'AAA AAAAAGACAA GATTGACATT AACATCAGAG CGGGTGAATT CGGGCAAAAA TTAGGCGATT GGCTCGTGTA TGTGGATAAG ACTGAAAACA ATTCCTATGA TAATTTGGTG CTTTTTTCTA ATAAAAGTCT CTCTCAAGAA AGCTTTATTT TGGCTCAAAA AGGCAATATC AACAATCAAA ACGGCGTGTT TGAATTGAAT TTGTATAACG GGCATGCGTA TTTCACTCAA GGCGATAAAA TGCGTAAGGT TGATTTTGAA GAATTGCATT TGCGCAACAA GCTCAAGTCT TTCAATTCTA ATGATGCGGC TTATTTGCAA GGCACGGATT ATTTGGGTTA TTGGAAAAAA GCCTTTGGTA AAAACGCTAA TAAAAATCAA AAACGCCGTT TTTCTCAAGC GATCTTAGTT TCCTTGTTCC CTTTAGCGAG CGTGTTTTTA ATCCCCTTAT TTGGCATCGC CAACCCGCGA TTCAAAACGA ATTGGAGTTA TTTCTATGTC CTTGGAGCG G TTGGGGTTTA TTTTTTAATG GTGCATGTGA TTTCTACGGA TTTGTTTTTG ATGACCTTTT TCTTCCCCTT TATTTGGGCG TTTATTTCTT ATTTATTGTT TAGAAAATTC No. 4:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 831 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, LOCATION 1 ... 831

(xi, SEQUENCE DESCRIPTION: SEQ ID NO: 4:

ATGAAGAAAA AAGCAAAAGT CTTTTGGTGT TGTTTTAAAA TGATTCGTTG GTTGTATTTG GCGGTCTTTT TTTTGTTGAG CGTATCAGAC GCTAAAGAAA TCGCTATGCA ACGATTTGAC AAACAAAACC ATAAGATTTT TGAAATCCTT GCGGATAAAG TGAGCGCCAA AGACAATGTG ATAACCGCCT CAGGGAATGC GATCCTATTG AATTATGACG TGTATATTCT AGCGGATAAG GTGCGTTATG ACACCAAGAC TAAAGAAGCG TTATTAGAAG GCAATATTAA GGTTTATAGG GGCGAGGGCT TGCTCGTTAA AACCGATTAT GTGAAATTGA GTTTGAACGA AAAATATGAG ATCATTTTCC CCTTTTATGT CCAAGACAGC GTGAGCGGGA TTTGGGTGAG CGCGGATATT GCTAGCGGGA AGGATCAAAA ATATAAGATT AAAAACATGA GCGCTTCAGG GTGCAGCATT GACAACCCCA TTTGGCATGT CAATGCGACT TCAGGCTCAT TTAACATGCA AAAATCGCAT TTGTCAATGT GGAATCCTAA GATTTATGTC GGCGATATTC CTGTATTGTA TTTGCCCTAT ATTTTCATGT CCACGAGCAA TAAAAGAACT ACCGGGTACG

120

180

240

300

360

420

480

540

600

660

720

780

840

900

960

1020

1038

120

180

240

300

360

420

480

540

600

660

113

TCCAACTTAG ACGGCTTTAT TTATTTGCAA CCCTTTTATT TAGCCCCCAA AAACTCATGG 720

GATATGACCT TTACCCCACA AATCCGTTAC AAAAGGGGTT TTGGCTTGAA TTTTGAAGCG 780

CGCTACATCA ACTCTAAGAC GCAGGTTTTT ATTCAATGCG CGCTATTTTA G 831 (2) INFORMATION ABOUT SEQ. NO. 5:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 675 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLDGIA: 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: various characters (B) LOCATION 1 ... 675 (xi) SEQUENCE DESCRIPTION: SEQ. NO. 5:

ATGATTAGAT TAAAAGGTTT GAATAAAACT TTAAAAACAA GCTTATTAGC TGGGGTTTTA 60 CTAGGTGCTA CTGCTCCCTT AATGGCAAAG CCTTTATTAA GCGATGAAGA CTTATTGAAA 120 CGAGTAAAAC TACACAATAT CAAAGAAGAT ACGCTGACTA GCTGTAATGC TAAGGTGGAC 180 GGCTCTCAAT ACTTGAATAG TGGTTGGAAT TTATCTAAAG AATTTCCGCA AGAATATAGA 240 GAAAAGATTT TTGAATGCGT AGAAGAAGAA AAACATAAAC AAGCCCTTAA TTTAATCAAT 300 AAAGAAGACA CTAAAGATAA AGAAGAACTT GCAAAAAAAA TCAAAGAAAT TAAAGAAAAA 360 GCTAAAGTTT TAAGGCAAAA ATTTATGGCT TTTGAAATGA AAGAACACTC TAAAGAATTC 420 CCAAATAAAA AGCAACTTCA AACCATGCTT GAGAACGCTT TTGATAATGG AGCTGAAAGT 480 TTTATTGATG ATTGGCACGA ACGCTTTGGG GGTATAAGTA GAGAGAATAC TTATAAAGCA 540 CTTGGCATTA ÄAGAATATAG TGATGAAGGA AAGATATTGC CTTTGGCGAA AGAAGTTATA 600 TTAGACAATA TAAAÄAAGAT TTTGAAGAAA GCACTTATGA TACTAGACAA CCCTTATCTG CTATGGCTAG Tatge 660 675 (2) INFORMATION ON SEQ. NO. 6:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 1290 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 ... 1290 (xi) SEQUENCE DESCRIPTION: SEQ. NO. 6:

ATGCCATACG CCTTAAGAAA AAGATTTTTC AAACGCCTTT TATTGTTTTT TTTAATTGTT 60

TGTATGATAA ATTTGCATGC CAAAAGCTAT CTGTTTTCTC CTTTGCCCCC AGCGCACCAG 120

CAAATCATTA AGACAGAGCC TTGCTCTTTG GAGTGCTTGA AAGACTTGAT GCTGCAAAAT 180

114

CAAATCTTTT CTTTTGTATC CCAATACGAT GATAACAACC AAGATGAGAG CCTTAAAACT 240 TATTACAAGG ACATCTTAAA CAAACTCAAC CCCGTATTCA TCGCTTCTCA AACTCCAGCT 300 AAAGAAAGCT ATGAGCCTAA GATTGAATTA GCGATTTTAC TGCCTAAAAA GGTGGTGGGC 360 CGTTATGCGA TTTTAGTGAT GAACACCCTT TTAGCGTATT TGAACACCAG AAACAACGAT 420 TTCAATATCC AAGTCTTTGA CAGCGATGAA GAAAGCCCTG AAAAATTAGA AGAAACC7AT 480 AAAGAAATTG AAAAAGAAAA ATTCCCTTTT ATCATCGCTT TATTGACTAA AGAGGGCGTG 540 GAAAATTTGC TCCAAAATAC GACTATCAAT ACCCCTACTT ATGTGCCTAC GGTGAATAAA 600 ACGCAATTAG AAAATCATAC CGAGCTTTCT TTAAGCGAGC GCTTGTATTT TGGGGGGATT 660 GATTATAAAG AGCAATTAGG CATGCTCGCA ACTTTCATTA GCCCTAATTC GCCCGTGATT 720 GAATACGATG ATGATGGCCT GATAGGTGAA CGCTTGAGGC AAATCACGGA GTCTTTAAAC 780 GTTGAAGTCA AACACCÄAGA AAACATTTCT TACAAACAAG CGACCAGTTT TTCTAAAAAT 840 TTTAGAAAAC ATGATGCGTT TTTTAAAAAT TCTACCTTAA TTTTGAACAC CCCTACCACT 900 AAAAGCGGTC TGATCCTTTC TCAAATAGGG CTTTTAGAGT ATAAGCCTCT TAAAATCCTT 960

TCCACACAAA TCAATTTCAA CCCCTCTTTA CTCTTGCTCA CCCAGCCTAA AGACAGGAAA 1020 AATTTATTCA TTGTCAATGC CTTGCAAAAC AGCGATGAAA CGCTGATAGA ATACGCTTCC 1080 TTATTAGAGA GCGATTTAAG GCATGATTGG GTGAA'ľTATT CCAGCGCGAT AGGGCTAGAG 1140 ATGTTTTTAA ACACGCTAGA TCCGCATTTT AAAAAGTCTT TTCAAGAGAG TTTGGAAGAC 1200 AATCAAGTCC GTTACCACAA TCAAATTTAT CAGGCTTTAG GGTATTCTTT TGAGCCGATA 1260 AAAAACGAAA GCGAAACAAA AAAAGAATAA 1290 (2) INFORMATION ON SEQ. No. 7:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 1368 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 ... 1368 (xi) SEQUENCE DESCRIPTION: SEQ. No. 7:

GTGTTAAAAT TTCAAAAATT ACCCTTATTG TTTGTTTCCA TTCTTTATAA TCAAAGCCCT 60 TTATTGGCTT TTGATTATAA GTTTAGTGGG GTAGCGGAAT CTGTTTCTAA AGTGGGGTTT 120 AACCATTCCA AACTCAATTC CAAAGAAGGG ATTTTCCCTA CAGCCACCTT TGTAACCGCC 180 ACGATCAAGC TTCAAGTGGA TTCCAATCTG CTCCCTAAAA ACATTGAAAA ACACAGCTTA 240 AAAATAGGCG TTGGGGGGAT TTTAGGAGCG CTCGCTTACG ATTCCACCAA AACGCTCATA 300 GACCAAGCCA CGCATCAAAT CTATGGCTCA GAACTTTTTT ACCTCATAGG GCGTTGGTGG 360 GGGTTTTTAG GCAACGCTCC TTGGAAAGAC TCCCTCATAG AATCTGACGC TCACACCCGT 420 AATTATGTGC TGTATAATTC CTATCTGTTT TATTCTTATG GCGATAAATT CCACCTAAAA 480 TTAGGGCGTT ATCTCTCTAA CATGGATTTT ATGAGTTCCT ACACACAGGG TTTTGAACTG 540 GATTATAAAA TCAATTCTAA AATAGCGTTA AAATGGTTTA GCTCTTTTGG GAGGGCGTTG 600 GCTTTTGGGC AATGGATACG GGATTGGTAT GCCCCTATTG TAACTGAAGA TGGCAGAAAA 660 GAAGTTTATG ATGGCATCCA TGCCGCGCAA CTCTATTTTT CTAGCAAGCA TGTTCÄAGTC 720 ATGCCTTTTG CTTATTTTTC GCCTAAGATT TACGGAGCGC CCGGTGTTAA AATCCATATT 780 GATAGCAACC CGAAATTCAA AGGCTTAGGG TTAAGGGCTC AAACCACTAT TAATGTGATT 840 TTCCCTGTTT ATGCTAAAG A TTTATACGAT GTGTATTGGC GTAACTCTAA GATTGGCGAG 900 TGGGGCGCAT CGCTTTTGAT CCACCAACGC TTTGACTACA ACGAATTTAA CTTTGGCTTT 960

GGTTATTACC AAAATTTTGG CAACGCTAAC GCAAGGATTG GCTGGTATGG TAACCCCATC 1020 CCTTTTAATT ATAGAAATAA CAGCGTTTAT GGTGGGGTCT TCAGTAACGC TATTACCGCA 1080 GACGCCGTTT CTGGGTATGT CTTTGGTGGG GGGGTGTATA GAGGGTTTTT ATGGGGTATT 1140 TTAGGCAGAT ACACTTATGC CACTAGAGCG AGCGAAAGAT CCATCAACTT GAACTTGGGC 1200 TATAAATGGG GTTCTTTTGC TAGAGTTGAT GTGAATTTAG AATACTATGT GGTCAGCATG 1260 CACAACGGCT ATAGATTAGA CTATCTCACC GGCCCTTTCA ACAAAGCCTT TAAGGCTGAC 1320 GCACAAGATA GGAGTAACCT TATGGTTAGC ATGAAATTCT TTTTTTAA 1368

115 (2) INFORMATION ABOUT SEQ. NO. 8:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 849 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 ... 849 (xi) SEQUENCE DESCRIPTION: SEQ. NO. 8:

ATGGGGTGTT CGTTTATCTT TAAAAAAGTT AGGGTTTATT CTAAAATGTT GGTTGCTTTG 60

GGGCTTTCAA GCGTGTTGAT CGGTTGCGCG ATGAATCCAA GCGCTGAGÄC AAAAAAACCA 120

AATGACGCCA AAAACCAACA ACCAGTTCAA ACTCATGAAA GAATGACAAC AAGTTCTGAA 180

CATGTTACGC CACTAGATTT TAATTACCCG GTGCATATTG TTCAAGCCCC ACAAAACCAT 240

CATGTTGTAG GTATTTTAAT GCCACGCATT CAAGTGAGCG ATAATCTAAA ACCCTATATT 300

GATAAGTTTC AAGACGCTTT AATTAATCAA ATCCAAACTA TTTTTGAAAA AAGAGGCTAT 360

CAAGTGTTGC GTTTTCAAGA TGAAAAAGCT TTGAATGTGC AAGATAAGAA AAAGATTTTT 420

TCCGTTTTGG ATTTGAAAGG GTGGGTAGGA ATCTTAGAAG ATTTGAAAAT GAATTTAAAA 480

GATCCCAATA GTCCCAATTT AGACACGCTA GTGGATCAAA GCTCAGGCTC TGTATGGTTT 540

AATTTTTATG AACCAGAAAG CAATCGTGTC GTCCATGATT TTGCTGTAGA AGTAGGAACT 600

TTTCAGGCAA TAACATACAC ATACACCTCT ACTAATAACG CTTCAGGAGG GTTTAATTCT 660

TCAAAAAGCG TTATCCATGA AAATTTGGAT AAGAATAGAG AAGACGCGAT ACACAAGATT 720

TTAAACAGAA TGTATGCGGT TGTCATGAAA AAAGCTGTAA CAGAACTTAC AAAAGAAAAT 780

ATCGCCAAAT ACAGAGACGC TATTGATAGA ATGAAAGGCT TTAAAAGTTC TATGCCTCAA 840

AAAAAGTAG 849 (2) INFORMATION ABOUT SEQ. No. 9:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 843 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) LOCATIONS 1 ... 843 (xi) SEQUENCE DESCRIPTION: SEQ. No. 9:

ATGAAACTGA GAGCAAGTGT TTTAATCGGT GTGGCAATTC TGTGCTTAAT TTTAAGTGCG 60 TGCAGTAACT ATGCGAAAAA AGTGGTGAAA CAAAAGAACC

116

TTCATGGTGC AAGTGAAGTT GCCAAATTAC AAGGACTATT TGTTGGATAA TAAACAAGTT 240 GTACTAACTT TCAAACTTGT TCACCATTCT AAAAAGATTA CGCTCATAGG CGATGCCAAT 300 AAGATCCTCC AATACAAGAA TTACTTCCAA GCTAACCGGG CAAGATCTGA CATTGATTTT 360 TACTTGCAAC CCACTTTGAA TCAAAAGGGT GTGGTGATGA TAGCGAGTAA CTACAATGAT 420 AATCCCAACA ACAAAGAAAA ACCACAGACC TTTGATGTGT TGCAAGGAAG TCAGCCAATG 480 CTAGGAGCTA ACACAAAAAA CTTGCATGGC TATGATGTGA GTGGAGCAAA CAACAAGCAA 540 GTGATCAATG AAGTGGCAAG AGAAAAAGCT CAGCTAGAAA AAATCAATCA GTATTACAAG 600 ACTCTCTTGC AAGACAAGGA ACAAGAATAT ACCACTAGGA AAAATAACCA ACGAGAAATT 660 TTAGAAACAT TGAGTAATCG TGCAGGTTAT CAAATGAGGC AGAATGTGAT TAGTTCTGAG 720 ATTTTTAAGA ATGGCAACTT GAACATGCAA GCCAAAGAAG AAGAAGTTAG GGAGAAGCTA 780 CAAGAAGAAA GAGAGAATGA ATACTTGCGC AATCAAATCA GAAGTTTGCT CAGTGGTAAG 840 TGA 843 (2) INFORMATION ON SEQ. No. 10:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 1179 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 ... 1179 (xi) SEQUENCE DESCRIPTION: SEQ. No. 10:

ATGAGAAAAC TATTCATCCC ACTTTTATTA TTCAGCGCTT TAGAAGCGAA CGAGAAAAAC 60 GGCTTTTTCA TAGAAGCCGG CTTTGAAACT GGGCTATTAG AAGGCACACA AACGCAAGAA 120 AAAAGACACA CCACCACAAA AAACACTTAC GCAACTTACA ATTATTTACC CACAGACACG 180 ATTTTAAAAA GAGCGGCTAA TTTATTCACC AATGCCGAAG CGATTTCAAA ATTAAAATTC 240 TCATCTTTAT CCCCTGTTAG AGTGTTGTAT ATGTATAATG GTCAATTAAC TATAGAAAAC 300 TTCTTGCCTT ATAATTTAAA TAATGTTAAG CTTAGTTTTA CAGACGCTCA AGGCAATGTG 360 ATCGATCTAG GCGTGATAGA GACTATCCCC AAACACTCTA AGATTGTTTT GCCCGGAGAG 420 GCATTTGATA GTCTAAAAAT TGACCCCTAT ACTTTATTTC TTCCAAAAAT TGAAGCCACT 480 AGCACTTCTA TTTCTGACGC TAACACGCAG AGGGTGTTTG AÄACGCTCAA TAAGATTAAG 540 ACAAATTTGG TCGTAAATTA TAGGAATGAA AACAAATTTA AAGATCACGA AAATCATTGG 600 GAAGCCTTTA CCCCACAAAC CGCAGAAGAA TTCACTAATT TAATGTTGAA CATGATCGCT 660 GTTTTAGACT CCCAATCTTG GGGCGATGCG ATCTTAAACG CTCCTTTTGA GTTCACTAAC 720 AGCCCAACAG ATTGCGATAA TGATCCTTCA AAATGCGTAA ATCCTGGGAC AAACGGGCTT 780 GTCAATTCTA AAGTCGATCA AAAATATGTG TTAAACAAAC AAGACATTGT CAATAAATTT 840 AAAAACAAAG CGGATCTTG A TGTAATTGTT TTAAAGGATT CAGGGGTTGT AGGGCTTGGG 900 AGTGATATTA CCCCTAGCAA CAATGATGAT GGCAAGCATT ATGGCCAGTT AGGGGTAGTA 960 GCTTCTGCTT TAGATCCTAA AAAACTCTTT GGCGATAACC TTAAGACTAT CAATTTAGAG 1020 GATTTAAGAA CCATCTTGCA TGAATTCAGC CACACTAAAG GCTATGGGCA TAACGGGAAT 1080 ATGACCTATC AAAGAGTGCC GGTAACGAAA GATGGTCAAG TGGAAAAGGA TAGTAATGGC 1140 AAGCCAAAAG ATTCTGATGG CCTCCCCTAT AATGTGTGT 1179 (2) INFORMATION ON SEQ. No. 11:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 813 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular (ii) MOLECULAR TYPE: DNA (genomic)

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

(A) ORGANISM: Helicobacter pylori (ix) SIGN: (A) NAME / KEY: different characters (B) PLACEMENT 1 ... 813

(xi) SEQUENCE DESCRIPTION: SEQ. No. 11:

ATGAAAAAGT TTGTAGCTTT AGGGCTTCTA TCCGCGGTTT TAAGCTCTTC GTTGTTAGCC 60 GAAGGTGATG GTGTTTATAT AGGGACTAAT TATCAGCTTG GACAAGCCCG TTTGAATAGC 120 AATATTTATA ATACAGGGGA TTGCACAGGG AGTGTTGTAG GTTGCCCCCC AGGTCTTACC 180 GCTAATAAGC ATAATCCAGG AGGCACCAAT ATCAATTGGC ACTCCAAATA CGCTAATGGG 240 GCTTTGAATG GTTTTGGGTT GAATGTGGGT TATAAGAAAT TCTTCCAATT CAAGTCGCTA 300 GATATGACAA GCAAGTGGTT TGGTTTTAGA GTGTATGGGC TTTTTGATTA CGGGCATGCC 360 GATTTAGGTA AACAAGTTTA TGCACCTAAT AAAATCCAGT TGGATATGGT CTCTTGGGGT 420 GTGGGGAGCG ATTTGTTAGC TGATATTATT GATAAAGACA ACGCTTCTTT TGGTATTTTT 480 GGTGGGGTCG CTATCGGCGG TAACACTTGG AAAAGCTCTG CAGCAAACTA TTGGAAAGAG 540 CAAATCATTG AAGCCAAAGG TCCTGATGTT TGTACCCCTA CTTATTGTAA CCCTAATGCC 600 CCTTATAGCA CCAACACTTC AACCGTCGCT TTTCAAGTGT GGTTGAATTT TGGGGTGAGA 660 GCCAATATCT ACAAGCATAA TGGCGTGGAA TTTGGCGTGA GAGTGCCGCT ACTCATCAAT 720 AAATTTTTGA GCGCGGGTCC TAACGCTACT AACCTTTATT ACCATTTGAA ACGGGATTAT 780 TCGCTTTATT TGGGGTATAA CTACACTTTT TAA 813 (2) INFORMATION O SEQ. No. 12:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 423 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 ... 423 (xi) SEQUENCE DESCRIPTION: SEQ. No. 12:

ATGCATCCTA TAATGTTTGC CTATATCGCT AACGCGCTCG CTCAAGCTAG AAAGATCAAC 60 GGAACACTTT GCATGGCGTT TCAAAAAATA TCTCAAGTCA AAGAATTAGG CATTGATAAA 120 GCAAAGAGTT TGATAGGCAA CCTTTCTCAA GTGATTATCT ACCCCACAAA AGATACTGAT 180 GAATTAATAG AATGTGGCGT CCCATTAAGC GATAGTGAAA TCAATTTCTT ACACAACACG 240 GACATGAGAG CCAGACAAGT GCTAGTAAAA AATATCGTTA CAAACGCTTC AGCTTTTATT 300 GAAATTGATT TAAAAAAGAT TTGCAAGAAC TACTTTATAT TCTTGATAGC AATGCTGGTA 360 ATAGAAAAAT CCTCAATGAT CTTAAAAAAG CAAACCAAGA AACTTATAAG GAAGAGTATT 420 TAA 423 (2) INFORMATION ABOUT SEQ. No. 13:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 771 base pairs (B) TYPE: nucleic acid

118 (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 ... 771 (xi) SEQUENCE DESCRIPTION: SEQ. No. 13:

ATGTTGGGGA GCGTCAAAAA AGCGGTTTTT AGGGTTTTGT GTTTGGGGGC GTTGTGTTTA TGCGGGGGGT TAATGGCAGA GCAAGATCCT AAAGAGCTTA TATTTTCAGG TATAACTATT TACACGGATA AAAATTTCAC TAGAGCTAAG AAATATTTTG AAAAAGCTTG CAAATCAAAC GATGCTGATG GCTGTGCAAT CTTAAGAGAG GTTTATTCTA GTGGTAAAGC CATAGCGAGA GAAAACGCAA GAGAGAGCAT TGAAAAAGCT CTTGAACACA CCGCTACTGC TAAAGTTTGT AAATTAAACG ATGCTGAAAA ATGCAAGGAC TTAGCAGAGT TTTATTTTAA TGTAAACGAT CTTAAAAATG CTTTAGAATA TTACTCTAAA TCTTGTAAGT TAAATAATGT TGAAGGGTGT ATGCTGTCAG CAACTTTTTA TAACGATATG ATAAAGGGTT TGAAAAAAGA TAAAAAAGAT CTAGAATATT ATTCTAAAGC TTGCGAGTTA AATAACGGTG GAGGGTGTTC TAAATTAGGA GGGGATTATT TTTTTGGTGA AGGCGTAACA AAAGATTTCA AAAAAGCTTT TGAATATTCT GCCAAAGCTT GTGAGTTGAA CGATGCTAAA GGGTGTTACG CTCTAGCAGC GTTTTATAAT GAGGGTAAAG GCGTGGCAAA GGATGAAAAG CAAACGACAG AAAACCTTGA AAAGAGTTGC AAGCTAGGAT TAAAAGAAGC ATGCGATATT CTCAAAGAAC AAAAACAATA and (2) INFORMATION ON SEQ. No. 14:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 729 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 ... 729 (xi) SEQUENCE DESCRIPTION: SEQ. No. 14:

ATGAAAAAAT TTTTTTCTCA ATCTTTGTTA GCTCTTATTA TCTCTATGAA TGCGGTATCT GGCATGGATG GTAATGGCGT TTTTTTAGGG GCGGGTTATT TGCAAGGACA GGCGCAAATG CATGCGGATA TTAATTCTCA AAAACAAGCC ACCAACGCTA CGATCAAAGG CTTTGACGCG CTCTTGGGGT ATCAATTTTT CTTTGAAAAA CACTTTGGCT TACGCCTTTA TGGGTTTTTT GACTACGCTC ATGCCAATTC TATTAAGCTT AAAAACCCTA ACTATAATAG CGAAGCGGCG CAAGTGGCTA GTCAAATTCT TGGGAAACAA GAAATCAATC GTTTAACAAA CATTGCCGAT CCCAGAACTT TTGAGCCGAA CATGCTCACT TATGGGGGGG CTATGGACGT GATGGTTAAT GTCATCAATA ACGGCATCAT GAGTTTGGGG GCTTTTGGCG GGATACAATT GGCCGGCAAT TCATGGCTTA TGGCGACACC GAGCTTTGAG GGCATTTTAG TGGAACAAGC CCTTGTGAGC AAGAAAGCCA CTTCTTTCCA ATTTTTATTC AATGTGGGGG CTCGCTTAAG GATCTTAAAA CATTCTAGCA TTGAAGCGGG CGTGAAATTC CCCATGCTAA AG

120

180

240

300

360

420

480

540

600

660

720

771

120

180

240

300

360

420

480

540

600

660

119

GCAAAAAATT TGGATATAGG GTTTAGGCGC GTGTATTCGT GGTATGTGAA TTACGTGTTC 720 ACTTTCTAG 729 (2) SEQ ID NO. No. 15:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 804 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 ... 804 (xi) SEQUENCE DESCRIPTION: SEQ. No. 15:

ATGAACTACC CTAATCTACC TAACAGCGCT TTAGAGATAA GCGAACAGCC AGAAGTGAAA 60 GAAATCACTA ACGAGCTTTT AAAGCAATTA CAAAACGCTT TAAGGAGCAA CGCGCATTTT 120 AGCGAGCAAG TGGAATTAAG CCTTAAATGC ATCGTTAGGA TTTTAGAAGT GCTTTTGAGT 180 TTGGATTTTT TTAAGAATGC GAATGAGATT GATAGCAGTT TAAGAAATTC CATTGAGTGG 240 CTGACTAACG CCGGCGAGAG CTTGAAATTA AAAATGAAAG AATACGAGCG CTTTTTTAGC 300 GAGTTTAATA CGAGCATGCA TGCCAACGAG CAGGAAGTAA CCAATACCTT AAACGCTAAC 360 GCCGAGAACA TTAAAAGCGA AATTAAAAAG CTAGAAAATC AATTGATAGA AACCACGACA 420 AGACTTTTAA CGAGCTATCA AATCTTTTTA AACCAAGCCA GAGATAACGC TAACAACCAA 480 ATCACAAAAA ACAAAACCCA AAGCCTTGAA GCGATTACAC AAGCTAAAAA CAACGCTAAT 540 AATGAAATAA GCAACAATCA AACGCAAGCG ATAACTAATA TCACCGAAGC GAAAACGAAC 600 GCTAATAATG AAATAAGCAA CAATCAAACG CAAGCGATAA CTAACATTAA CGAAGCCAAA 660 GAAAGCGCTA CAACGCAAAT AAACGCCAAT AAGCAAGAAG CAATAAATAA CATCACGCAA 720 GAAAAAACCC AAGCCACAAG CGAGATCACC GAAGCGAAAA AGACCGATCA TTATCAAAAC 780 ATTGATTTTT TTGAGTTTGA ATAA 804 (2) INFORMATION SEQ. No. 16:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 1632 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 ... 1632 (xi) SEQUENCE DESCRIPTION: SEQ. No. 16:

GTGATAGAGA CCATCCCCAA ACACTCTAAG ATTGTTTTAC CCGGGGGGGC GTTTGATAGT 60 TTAAAAGAGG CGTTTGATAA AATTGACCCC TATACTTTCT TTTTTCCAAA ATTTGAAGCC 120

120

ACTAGCACTT CTATTTCTGA TACTAACACG CAGAGGGTGT TTGAAACGCT CAATAACATT AAAACAAATC TTATAATGAA ATATAGTAAT GAAAATCCAA ACAATTTCAA CACTTGTCCT TACAATAATA ATGGTAATAC AAAAAATGAT TGTTGGCAAA ATTTCACCCC ACAAACCGCA GÄAGAATTCA CCAATTTAAT GTTGAACATG ATCGCTGTCT TAGACTCCCA ATCTTGGGGC GATGCGATCT TAAACGCTCC TTTTGAATTC ACTAAGAGCT CAACAGATTG CGATAGCGAT CCTTCAAAAT GCGTAAATCC CGGAGTAAAT GGGCGTGTTG ATACTAAAGT CGATCAACAA TATATACTCA ACAAACAAGG TATTATTAAT AATTTTAGAA AAAAAATAGA AATTGATGCG GTTGTTTTAA AAAATTCAGG GGTTGTAGGG TTAGCCAATG GATATGGCAA TGATGGTGAA TATGGCACAT TAGGGGTAGA AGCCTATGCT TTAGATCCTA AAAAACTCTT TGGCAACGAC CTTAAGACTA TCAATTTAGA AGATTTÄAGA ACCATCTTGC ATGAATTCAG CCACACTAAA GGCTATGGGC ATAACGGGAA TATGACCTAT CAAAGAGTGC CGGTAACGAA AGATGGTCAA GTGGAAAAGG ATAGTAATGG CAAGCCAAAA GATTCTGATG GCCTCCCCTA TAATGTGTGT TCGCTTTATG GGGGATCCAA TCAGCCCGCT TTCCCTAGCA ACTACCCTAA TTCCATCTAT CACAATTGTG CGGATGTCCC GGCTGGCTTT TTAGGGGTAA CAGCAGCGGT TTGGCAGCAG CTCATCAATC AAAACGCCTT GCCGATCAAC TACGCTAAGT TGGGGAGTCA AACAAACTAC AACCTAAA CG CTAGTTTAAA CACGCAAGAT TTAGCCAATT CCATGCTCAG CACCATCCAA AAAACCTTTG TAACTTCTAG CGTTACCAAC CACCATTTTT CAAACGCATC GCAAAGTTTT AGAAGCCCTA TTTTAGGGGT TAACGCTAAA ATAGGCTATC AAAACTACTT TAATGATTTC ATAGGGTTGG CTTATTATGG CATCATCAAA TACAATTACG CTAAAGCTGT TAATCAAAAA GTCCAGCAAT TGAGCTATGG TGGGGGGATA GATTTGTTAT TGGATTTCAT CACCACTTAC TCCAATAAAA ATAGCCCTAC AGGCATTCAA ACCAAAAGGA ATTTTTCTTC ATCTTTTGGT ATCTTTGGGG GGTTAAGGGG CTTGTATAAC AGCTATTATG TGTTGAACAA AGTCAAAGGA AGCGGCAATT TAGATGTGGC TACCGGGTTG AACTACCGCT ATAAGCATTC TAAATATTCT GTAGGGATTA GCATCCCTTT AATCCAAAGA AAAGCTAGCG TCGTTTCTAG CGGTGGCGAT TATACGAACT CTTTTGTTTT CAATGAAGGG GCTAGCCACT TTAAGGTGTT TTTCAATTAC GGTGGGTGTT TT (2) SEQ ID NO. No. 17:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH; 1071 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 ... 1071 (xi) SEQUENCE DESCRIPTION: SEQ. No. 17:

TTGATGAAAA GCATTTTGCT CTTTATGATT TTTGTAGTTT GTCAGTTAGA AGGCAAAAAA TTTTCACAAG ATAATTTTAA GGTGGATTAT AACTACTATT TGCGCAAACA GGATTTGCAC ATCATTAAÄA CGCAAAACGA TTTGTCCAAT GCCTGGTATC TCCCTCCACA AAAAGCCCCC AAAGAACATT CTTGGGTGGA TTTTGCTAAA AAATATTTAA ACATGATGGA TTATCTAGGC ACTTATTTTT TGCCTTTTTA TCATAGTTTC ACCCCCATTT TTCAATGGTA CCACCCTAAT ATCAACCCCT ACCAACGCAA TGAGTTTAAG TTCCAAATCA GTTTTAGAGT GCCTGTATTT AGGCATATTC TTTGGACTAA AGGCACGCTT TATCTGGCTT ATACCCAAAC TAACTGGTTT CAAATTTATA ATGACCCTCA ATCCGCCCCC ATGCGAATGA TCAATTTCAT GCCTGAACTC ATCTATGTTT ATCCTATTAA TTTTAAACCT TTTGGGGGTA AAATAGGGAA TTTTTCTGAA ATTTGGATAG GTTGGCAGCA CATTTCTAAT GGTGTGGGGG GTGCGCAATG TTACCAGCCT TTTAATAAAG AAGGTAATCC TGAAAACCAG TTTCCAGGAC AACCTGTAAT CGTTAAAGAT TATAACGGGC AAAAAGATGT GCGCTGGGGG GGGTGTCKTT CGGTGARCSC GGGCAACSCC CTGTGTTTCG TTTTGGTGTG GGAAAAGGGA GGCCTAAAAA TCATGGTCGC TTATTGGCCC TATGTCCCTT ATGATCAATC CAACCCTCAA TTGATTGATT ACATGGGGTA TGGTAACGCT AAAATTGATT ACAGGAGAGG GCGCCACCAT TTTGAATTGC AACTTTATGA TATTTTCACG CAATACTGG C GTTATGATCG CTGGCATGGA GCTTTCCGCT TAGGCTATAC CTACCGCATT

180

240

300

360

420

480

540

600

660

720

780

840

900

960

1020

1080

1140

1200

1260

1320

1380

1440

1500

1560

1620

1632

120

180

240

300

360

420

480

540

600

660

720

780

840

900

960

121

AACCCTTTTG TGGGGATTTA TGCGCAGTGG TTTAACGGCT ATGGCGATGG CTTGTATGAA 1020 TACGATGTTT TTTCCAATCG TATAGGGGTA GGAATACGCT TGAACCCTTA A 1071 (2) SEQ ID NO. No. 18:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 2028 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 ... 2028

(xi) SEQUENCE DESCRIPTION: SEQ. No. 18:

TTGTCTAAAG GTTTGAGTAT CGGTAATAAA ATCATATTGT GCGTGGCGTT GATTGTGATC 60 GTGTGCGTGA GCATTTTAGG GGTGTCCTTA AACAGCAGGG TGAAAGAGAT TTTAAAAGAA 120 AGCGCTCTGC ATTCAATGCA AGATAGTTTG CATTTCAAGG TTAAGGAAGT GCAAAGTGTT 180 TTGGAAAACA CTTATACGAG CATGGGCATT GTCAAAGAAA TGCTCCCTGA AGACACCAAA 240 AGAGAAATCA AAATCCAGTT GTTAAAAAAC TTCATTTTAG CCAATTCGCA TGTCGCTGGG 300 GTGAGCATGT TTTTTAAAGA CAGAGAGGAT TTGAGATTGA CGCTTTTACG AGATAACGAT 360 ACGATCAAGT TGATGGAAAA CCCGTCATTA GGGAGTAACC CTTTAGCGCA AAAAGCGATG 420 AAAAATAAAG AAATTTCTAA AAGCTTGCCT TATTACAGGA AAATGCCTAA CGGGGCGGAA 480 GTTTATGGCG TGGATATTCT TTTACCACTA TTCAAGGAAA ACACGCAAGA AGTGGTGGGG 540 GTTCTGATGA TTTTCTTTTC CATTGACAGC TTCAGTAATG AAATCACTAA AAACAGGAGC 600 GATTTATTTT TAATTGGCGT TAAAGGTAAA GTGCTTTTGA GCGCGAATAA AAGCTTGCAA 660 GACAAATCCA TCACCGAAAT TTATAAAAGC GTGCCTAAAG CCACTAATGA AGTGATGGCT 720 ATTTTAGAAA ATGGCTCTAA AGCGACTTTA GAATACTTGG ATCCCTTTAG CCATAAGGAG 780 AATTTTTTAG CCGTTGAAAC CTTTAAAATG CTAGGCAAAA CAGAAAGTAA AGACAATCTT 840 AATTGGATGA TCGCTTTGAT CATTGAAAAA GACAAGGTCT ATGAGCAAGT GGGATCGGTG 900 CGTTTTGTGG TGGTTGCAGC GAGTGCTATC

CTTTTAATGC GAGCGATCGT GAGCAATCGT TTGGAAGTCG TTTCTAGCAC CTTGTCTCAT 1020

TTCTTTAAAT TATTGAACAA TCAAGCCCAT TCTAGCGACA TTAAATTGGT TGAAGCGCGA 1080

TCTAATGACG AATTAGGGCG CATGCAAACA GCGATCAATA AAAATATCTT GCAAACCCAA 1140

AAAACCATGC AAGAAGACAG GCAAGCCGTC CAAGACACCA TTAAAGTGGT TTCAGACGTG 1200

AAAGCGGGGA ATTTTGCGGT GCGCATCACG GCTGAACCCG CAAGCCCTGA TTTGAAAGAA 1260

TTGAGAGACG CGCTAAATGG GATCATGGAT TATTTGCAAG AAAGCGTAGG GACTCACATG 1320

CCAAGCATTT TCAAAATCTT TGAAAGCTAT TCTGGCTTGG ATTTTAGAGG GCGGATCCAA 1380

AACGCTTCGG GTAGGGTGGA ATTGGTTACT AACGCTTTAG GGCAAGAAAT CCAAAAAATG 1440

CTAGAAACTT CGTCTAATTT TGCCAAAGAT CTAGCGAACG ATAGCGCGAA TTTAAAAGAA 1500

TGCGTGCAAA ATTTAGAAAA GGCTTCAAAC TCCCAACACA AAAGCCTGAT GGAAACTTCC 1560

AAAACGATAG AAAATATCAC CACTTCCATT CAAGGCGTGA GCTCTCAAAG TGAAGCCATG 1620

ATTGAACAAG GGAAAGACAT TAAAAGCATT GTAGAAATCA TTAGAGATAT TGCCGATCAA 1680

ACGAATCTAT TAGCCCTAAA CGCTGCTATT GAAGCCGCAC GAGCCGGCGA GCATGGCAGA 1740

GGCTTTGCGG TGGTGGCTGA TGAGGTGAGG AAGCTCGCTG AAAGGACGCA AAAATCCCTC 1800

AGTGAGATTG AAGCCAATAT TAATATTCTC GTTCAAAGCA TTTCAGACAC GAGCGAAAGC 1860

ATTAAAAACC AGGTTAAAGA AGTAGAAGAG ATCAACGCTT CTATTGAAGC CTTAAGATCG 1920

GTTACTGAGG GCAATCTAAA AATCGCTAGC GATTCTTTAG AAATCAGTCA AGAAATTGAC 1980

AAAGTCTCTA ACGATATTTT AGAAGATGTG AATAAAAAGC AGTTTTAA 2028 (2) INFORMATION ABOUT SEQ. No. 19:

(i, SEQUENCE CHARACTERISTICS:

(A) LENGTH: 816 base pairs (B) TYPE: nucleic acid

122 (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 ... 816 (xi) SEQUENCE DESCRIPTION: SEQ. No. 19:

ATGAACATAT TCAAGCGTAT TATTTGCGTA ACCGCTATTG TTTTAGGTTT TTTTAACCTT 60 TTAGACGCCA AACACCACAA AGAAAAAAAA GAAGAC.'CACA AAATCACTCG TGAGCTTAAA 120 GTGGGCGCTA ACCCTGTGCC GCATGCGCAA ATCTTGCAAT CAGTTGTGGA TGATTTGAAA 180 GAGAAAGGGA TCAAATTAGT GATCGTGTCT TTTACGCATT ATGTGTTGCC TAATTTAGCG 240 CTCAATGACG GCTCTTTAGA CGCGAATTAC TTCCAGCACC GCCCTTATTT GGATCGGTTT 300 AATTTGGACA GAAAAATGCA CCTTGTTGGT TTGGCCAATA TCCATGTGGA GCCTTTAAGA 360 TTTTATTCTC AAAAAATCAC AGACATTAAA AACCTTAAAA AAGGCTCAGT GATTGCTGTG 420 CCAÄATGATC CGGCCAATCA AGGCAGGGCG TTGATTTTAC TCCATAAACA AGGCCTTATC 480 GCTCTCAAAG ACCCAAGCAA TCTATACGCT ACGGAGTTTG ATATTGTCAA AAATCCTTAC 540 AACATCAAAA TCAAACCCCT AGAAGCTGCG TTATTGCCTA AGGTTTTAGG GGATGTGGAT 600 GGGGCTATCA TAACAGGGAA TTATGCCTTG CAAGCAAAAC TCACCGGAGC CTTATTTTCA 660 GAAGATAAGG ACTCGCCTTA TGCTAATCTT GTAGCCTCTC GTGAGGATAA TGCGCAAGAT 720 GAAGCGATAA AAGCGTTGAT TGAAGCCTTA CAGAGCGAAA AGACCAGGAA ATTCATTTTG 780 GATACCTATA AGGGGGCGAT TATCCCGGCT TTTTAA 816 ( 2, SEQ ID NO: 20:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 486 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 ... 486 (xi) SEQUENCE DESCRIPTION: SEQ. No. 20:

ATGTTTTTTA AAACTTATCA AAAATTACTG GGCGCGAGCT GTTTGGCGCT GTATTTAGTG 60 GGCTGTGGGA ATGGTGGTGG CGGTGAATCG CCGGTTGAGA TGATTGCAAA TAGCGAGGGT 120 ACGTTTCAAA TCGACTCCAA AGCAGATAGC ATTACTATTC AAGGCGTGAA GCTTAATAGA 180 GGTAATTGTG CTGTCAATTT TGTTCCAGTA AGTGAGACGT TTCAAATGGG TGTTTTAAGT 240 CAAGTTACTC CAATCTCTAT ACAGGATTTT AAAGATATGG CAAGCACTTA TAAGATATTT 300 GATCAAAAGA AAGGGTTGGC AAACATAGCA AATAAAATTT CTCAATTAGA GCAAAAGGGT 360 GTGATGATGG AACCTCAAAC CCTTAATTTT GGAGAAAGTT TAAAAGGCAT TTCTCAAGGG 420 TGCAATATTA TAGAGGCAGA AATACAAACC GACAAAGGCG CTTGGACTTT TAACTTTGAT 480 AAATAA 486

123 (2) INFORMATION ABOUT SEQ. No. 21:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 1014 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 ... 1014 (xi) SEQUENCE DESCRIPTION: SEQ. No. 21:

ATGATTAGAT TAÄAAGGTTT GAATAAAACT TTAAAÄACAA GCTTATTAGC TGGGGTTTTA 60

CTAGGTGCTA CTGCTCCCTT AATGGCAAAG CCTTTATTAA GCGATGAAGA CTTATTGAAA 120

CGAGTAAAAC TACACAATAT CAGAAGAAGAT ACGCTGACTA GCTGTAATGC TAAGGTGGAC 180

GGCTCTCAAT ACTTGAATAG TGGTTGGAAT TTATCTAAAG AATTTCCGCA AGAATATAGA 240

GAAAAGATTT TTGAATGCGT AGAAGAAGAA AAACATAAAC AAGCCCTTAA TTTAATCAAT 300

AAAGAAGACA CTGAAGATAA AGAAGAACTT GCAAAAAAAA TCAAAGAAAT TAAAGAAAAA 360

GCTAAAGTTT TAAGGCAAAA ATTTATGGCT TTTGAAATGA AAGAACACTC TAAAGAATTC 420

CCAAATAAAA AGCAACTTCA AACCATGCTT GAGAACGCTT TTGATAATGG AGCTGAAAGT 480

TTTATTGATG ATTGGCACGA ACGCTTTGGG GGTATAAGTA GAGAGAATAC TTATAAAGCA 540

CTTGGCATTA AAGAATATAG TGATGAAGGA AAGATATTAG CCTTTGGCGA AAGAAGTTAT 600

ATTAGACAAT ATAAAAAAGA TTTTGAAGAA AGCACTTATG ATACTAGACA AACCTTATCT 660

GCTATGGCTA ATATGAGTGG CGAAAACGAT TATAAAATTA CTTGGTTAAA ACCCAAATAT 720

CAGCTCCATA GTTCAAATAA TATTAAACCC TTAATGTCAA ACACAGAGTT GTTAAATATG 780

ATAGAGCTAA CCAATATCAA AAAAGAATAT GTTATGGGCT GTAATATGGA AATAGATGGT 840

TCTAAATATC CCATTCATAA AGATTGGGGA TTTTTTGGTA AGGCAAAAGT CCCAGAAACT 900

TGGAGAAATA AGATTTGGGA ATGTATTAAG AATAAAGTAA AGTCCTATGA CAACACTACC 960

GCTGAAATAG GAATAGTTTG GAAAAAAAAT ACTTATTCTA TCTCTCATCA CTAA 1014 (2) INFORMATION ABOUT SEQ. No. 22:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 1251 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 ... 1251 (xi) SEQUENCE DESCRIPTION: SEQ. No. 22:

ATGAAAAAAT TAGTTTTTAG CATGCTTTTA TGTTGTAAAA GCGTGTTTGC AGAGGGGGAA

ACTCCTTTGA TTGTCAATGA CCCAGAAACC CATGTAAGTC AAGCCACTAT CATAGGCAAA 120

124

ATGGTAGATA GTATCAAAAG ATACGAAGAG ATTATTTCTA AGGCTCAAGC TCAAGTCAAT 180 CAGTTACAAA AAGTCAATAA CATGATAAAT ACGACTAATT CTTTGATTAG TAGTAGTGCT 240 ATCACTTTAG CCAATCCTAT GCAAGTTTTA CAAAACGCTC AGTATCAAAT AGAGAGCATT 300 AGATACAACT ATGAGAATTT AAAGCAAAGC ATAGAAAATT GGAACGCACA AAATTTGTTA 360 AGAAACAAAT ACTTACAGCA ACAATGCCCT TGGCTTAATG TCAATGCTCT TACTAACAAT 420 AAGATTGTCA ATCTTAAAGA TCTCAATAAC CTAATCACCA AAAATCGCGA ACAAACCCAA 480 ACCGCAAGAG ATGTGCAAAA TCTCATTCAG TCCATTAGTG GCAGTGGCTA TGGAAACATG 540 CAATCACTTG CTGGGGAATT GAGTGGTAGA GCGTGGGGGG AAATGTTGTG TAAAATGGTA 600 AACGATAGTA ATTATGAAAG CGAGCAAGCT CTTTTAGCAA CAGGCAATAA CCCAGAAGAG 660 CÄAAAACGAA GATTTTTGCT TAGAGTAAAG AAAAAGGTTA ATGATAATAA GCAGTTAAAA 720 GATAAACTTG ACCCATTTCT AAAAAGACTT GATGTCCTAC ÄAACTGAGTT TGGTGTAACT 780 GACCCTACAG CTAACCATAA TAAGCAAGGG ATACATTATT GCACAGAAAA TAAAGAGACA 840 GGTAAATGCG ACCCTATTAA AAATGTATTT AGGACAACTC GCTTAGATAA CGAATTAGAA 900 CAAGAAATCC AAACGCTCAC ACTTGATTTA ATCAAAGCCT CCAATAAAGA CGCTCAAAGC 960 CAAGCCTACG CAAATTT CAA TCAAAGGATT AAATTACTTA CTCTAAAATA TTTAAAAGAA 1020 ATTACCAATC AAATGCTCTT TTTAAATCAA ACAATGGCAA TGCAAAGCGA GATTATGACA 1080 GATGATTATT TTAGGCAAAA TAATGATGGC TTTGGGGAAA AAGAAAACCA TATAGACAAA 1140 CAATTAACGC AAAAAAGAAT AAACGAAAGA GAAAGAGCTA GAATATAC'TT TCAAAACCCT 1200

AATGTTAAAT TTGACCAATT TGGCTTTCCC ATTTTTAGTA TATGGGATTA A 1251 (2) INFORMATION ABOUT SEQ. No. 23:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 1131 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 ... 1131 (xi) SEQUENCE DESCRIPTION: SEQ. No. 23:

GTGAATAAGT GGATTAAAGG GGCGGTTGTT TTTGTAGGGG GTTTTGCAAC GATTACAACC 60 TTTTCTTTAA TCTACCACCA AAAGCCAAAA GCCCCCCTAA ATAACCAGCC TAGCCTTTTG 120 AATGACGATG AGGTGAAATA CCCCTTACAA GACTACACTT TCACTCAAAA CCCACAGCCA 180 ACTAACACGG AAAGCTCCAA AGACGCTACC ATCAAAGCCT TACAAGAACA GCTCAAAGCC 240 GCTTTAAAAG CCCTAAACTC CAAAGAAATG AATTATTCCA AAGAAGAGAC TTTTACTAGC 300 CCTCCCATGG ATCCAAAAAC AACCCCCCCT AAAAAAGACT TTTCTCCAAA ACAATTAGAT 360 TTACTGGCCT CTCGCATCAC CCCTTTCAAG CAAAGCCCTA AAAATTACGA AGAAAACCTG 420 ATTTTCCCTG TGGATAACCC TAATGGCATT GATAGTTTCA CTAACCTTAA ÄGAAAAAGAC 480 ATCGCCACTA ATGAAAACAA GCTTTTACGC ACCATTACAG CTGACAAAAT GATACCCGCT 540 TTTTTGATTA CGCCCATTTC TAGCCAGATC GCTGGTAAAG TGATTGCGCA AGTGGAGAGC 600 GATATTTTTG CAAGCATGGG CAAAGCCGTC TTAATCCCCA AAGGCTCTAA AGTCATAGGC 660 TATTACAGCA ACAATAACAA AATGGGCGAA TACCGCTTGG ATATTGTATG GAGTCGAATC 720 ATCACTCCCC ATGGCATTAA TATCATGCTC ACTAACGCTA AAGGGGCGGA CATTAAAGGC 780 TATAACGGCT TAGTGGGGGA ATTGATTGAA AGGAATTTCC AACGCTATGG CGTGCCGTTA 840 CTGCTTTCTA CGCTCACTA A CGGCCTATTG ATTGGGATCA CTTCGGCTTT AAACAACAGA 900 GGCAATAAAG AAGAGGTGAC TAATTTCTTT GGGGATTATC TTTTATTGCA ATTGATGAGG 960 CAAAGCGGCA TGGGGATCAA TCAAGTGGTC AATCAAATTT TAAGAGACAA GAGCAAGATC 1020 GCCCCCATTG TGGTGATTAG AGAGGGGAGT AGGGTCTTCA TTTCGCCCAA TACTGACATC 1080 TTCTTCCCTA TACCCAGAGA GAATGAAGTC ATCGCTGAGT TTTTGAAGTG A 1131 (2) INFORMATION ON SEQ. No. 24:

(i) SEQUENCE CHARACTERISTICS:

125 (A) LENGTH: 2751 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 ... 2751 (xi) SEQUENCE DESCRIPTION: SEQ. No. 24:

GTGGATTTGA GGATCCAATC TAAAGAAGTC AGTCATAATT TAAAGGAATT ATCAAAAACG 60

CTAATCAGCT ATCCTTTTGA AAAACATGTA GAAGCTTTAG GGGAACAATG CAGTAACTTC 120

GTTTCTATTC CCATTAACAA TGACGACTAT TCAAATATTT GCACTTTTGT GAGTGATTTT 180

ATAAATCTTA TAGCTTCTTA CATATTTATTA GAATCATTTT TAGATTTTTA TAAAGATAAA 240

TTAAAATTGA GCGAGCTTGT AACTGAATAT GCCAACGTAA CCAATAATCT GCTTTTCAAA 300

AAATTAATCA AACATTTAAG CGAGCAACAAT CAÄTTGGTTA AAAATTTTTA TCAGTGTATA 360

AGAGAAATTA TAAAATACAA CGCCCCTAAT AAAGAATACA AACCCAATCA ATTTTTTATA 420

ATAGGGAAAG GCAAACAAAA ACAATTAGCA AAAATTTATT CTCATTTAAA AGAACTTAGT 480

GCAAGTGAAA TTAAACCACA AGATATGGAA GACATCTTAA AAAAGCTAGA GGAATTAGAT 540

AAAATTTTTA AAACTACCGA CTTTACAAAA TTCACACCAA AAACTGAAAT TAAGGATATT 600

ATTAAAGAAA TAGACGAAAA ATACCCTATC AATGAAAATT TTAAACGGCA ATTTAATGAG 660

TTTGAATCAA ATATTGAAAA ACATGATGAA ATAAAAAAGG ATTTTGAGCG AAACAAAGAG 720

TCGCTGATCC GAGAAATTGA AAATCACTGC AAAAATGAAT GCAATAGCGA AGAAGAGCCG 780

GAGTATAAGA TTAATGATCT GCTCAAAAAT ATCCAACAAA TATGCAAAAA TTATATAGAA 840

AGTCATGCCG TTAATGATGT GTCTAAAGAT ATTAAATCCA TGATGTGTCA GTTTTATTTG 900

AAACAGATAG ATTTATTAGT CAATTCAGAA ATTGTGCGAT ACAGATACAG CAATCTTTTT 960

GAÄCCAATAC AAAGATCTTT ATGGGAGAGT ATAAAAATTT TAGATAATGA AAGTGGCATT 1020

TATTTGTTCC CTAAAAATAT TGGTGAAATC AAGGATAAAT TTGAAGCAAA CAAGGAAAAA 1080

TTCAAACAAA GCAAAAATGT TTCTGAGTTC GCAGAATATT GCCGAGAGTG TAACCCCTAT 1140

ACAGCGTTTA ACTTTCATCT AAATATAAAT AATGGTTTAT CTCATCAATT TGAAAAATTC 1200

GTGCCAATCA TGAAAGAATA CAAAGAGCCA AAAATCACAG ATAATGACCT TGAAGCCATA 1260

TCAACCAAAG AGACTGGTCT TGCTAGCCAA TTATCTGGGC ACTGGTTTTT TCAGCTTTCG 1320

TTATTTAATA AAACAAACTT TAATCCTAAT AAAATTTGGA TTCCTTTAGA GTTCAATAAA 1380

AGATCAAAAA TAAAGTTTGA TAAAGATTTA GAAATCTATT TTGATAGTCA TGAATCGTTC 1440

AATATCTCTA AAAAATACTT GCAAGAAATA GATCAAGAAT CACTAAAAAA GATCAAACAA 1500

TCAAAAGATT TTTTTTCAAT TCAAAAAATA GAGAGTAAGC ATGATAATAA CGATATACTG 1560

CAACTTGAAT TTTTTGAGAA TGATACAAGT TTTCTTTTTG CTAAAGGAAG TTTTGCAGAA 1620

ATTTTAGAAT ACAACATGCA ATTAAAAATA GATTCTTTAA TTACAAAAGA ATTTAATAAG 1680

CTTTTAGCGA TCGTTCAAGA TAGTCCCCAA GATAGTTACC AATTAAAAAT TCGTGTCCGA 1740

CATAACAATA AGCTTCCTAG AGAGAAATAT ACGGAACATG AAATAAAACT TGAAGTTTAT 1800

GATTGCAGAA AATCCCACGA TCACAATGAG CCAATCATCT TAAGCCAGCA AAGCACCGGC 1860

TTCCAATGGG CGTTTAATTT CATGTTTGGC TTTCTTTATA ATGTGGGATC ACATTTTAGT 1920

TTTAACCATA ATATTATCTA TGTCATGGAC GAGCCAGCCA CTCATTTGAG CGTGCCAGCC 1980

AGAÄAGGAGT TTAGGAAATT TTTAAAAGAA TACGCTCATA AAAATCATGT TACTTTTGTT 2040

TTAGCCACCC ATGACCCCTT TTTAGTGGAT ACGGATCATT TAGATGAAAT AAGGATTGTG 2100

GAÄAAGGAAA CAGAAGGCTC TGTAATTAAG AATCACTTTA ACTATCCCCT AAATAATGCA 2160

AGCAAAGACT CCGACGCTTT GGACAAAATC AAACGCTCTT TAGGAGTGGG CCAGCATGTT 2220

TTTCATAACC CCCAAAAACA CCGAATCATT TTTGTAGAAG GCATCACGGA TTATTGTTAT 2280

TTGAGCGCTT TTAAATTGTA TTTGCGTTAC AAAGAATACA AGGACAACCC CATTCCTTTC 2340

ACTTTCTTAC CCATTTCAGG GCTTAAAAAC GATTCAAACG ATATGAAAGA AACCATTGAA 2400

AAACTTTGCG AGTTAGACAA TCACCCTATT GTTTTGACAG ACGATGACAG AAAATGCGTT 2460

TTTAACCAAC AAGCAACGAG CGAACGATTT AAAAGAGCTA ATGAAGAAAT GCATGATCCC 2520

ATCACCATCC TACAACTCTC AGACTGCGAT AGGCATTTCA AACAAATTGA AGATTGTTTC 2580

AGCGCAAACG ATAGAAACAA ATACGCTAAA AATAAGCAAA TGGAATTGAG CATGGCTTTT 2640

AAAACAAGGC TTTTGTATGG CGGAGAAGAT GCGATAGAAA AACAAACAAA AAGAAATTTT 2700

TCAAAATTAT TCAAATGGAT TGCATGGGCT ACAAACTTGA TCAAAAACTA A 2751

126 (2) INFORMATION ABOUT SEQ. No. 25:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 531 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 ... 531

(xi) SEQUENCE DESCRIPTION: SEQ. No. 25:

ATGACTGCAA TGATGCGTTA CTTCTTTTTG CGGTTAGTGG AAGATCAAAG AATGGGTTTT AAAGGCTTTA TAAAAGAAAA AGGGGAGCGT TAGTCATTGG CAAACGAAAA TCAAGACCAT GCTAAGGTGTGTGTGTGTGTGTGTGTGTGTGT

TTTTCACATC TATGCGACCA GCTTTCATTG CTCTTTAAAG AGAAAAAATCC TTAAAAAAAG CCATATCGCT ATGCCTAAAA CACGCCTTTG TATGAAATCA TGAAAGGGGC

CTTTTTTCTT

CGCGCCAAGA

AAGAACGATT

AGATAGAGCC

ACCTTGAAAC

CGCTCATCAT

TTTGCGTGTT

CTAAACGCAT

GGTCTTTGTA

CCCTTTGGCG

CACTGGCGCT

GGACTTTTTA

TAGAGAGTAT

TAAAGGCACT

GCTGCATAAG

TTTATTGTTG

GTTTATAAGC

G

120

180

240

300

360

420

480

531 (2) INFORMATION ABOUT SEQ. No. 26:

(i, SEQUENCE CHARACTERISTICS:

(A) LENGTH: 669 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 ... 669 (xi, SEQUENCE DESCRIPTION: SEQ ID NO: 26:

ATGTTTAAAA ACGCTTTAAA TATACAAGAT TTTTCATTTA AAAATCATAC TAGTACAGCC 60 ATTATTGGCA CAAATGGTGC TGGAAAATCA ACGCTTATCA ACACTATTCT AGGCATTAGA 120 TCAGACTATA ATTTTAAAGC ACAAAACAAT AATATTCCAT ACCACGACAA TGTTATACCA 180 CÄACGCAAGC AATTGGGAGT TGTCTCTAAC CTATTCAACT ACCCACCTGG ATTAAACGCA 240 AACGACCTTT TTAAATTCTA TCAATTTTTT CACAAAAACT GCACTCTAGA TTTGTTTGAA 300 AAAAATCTTT TAAATAAAAC CTACGAACAC CTAAGCGACG GACAAAAACA GCGCTTAAAA 360 ATTGACTTAG CTCTTAGCCA TCACCCACAA TTAGTTATTA TGGATGAACC AGAAACCAGT 420 TTAGAGCAAA ACGCTCTTAT AAGACTATCA AATCTCATAA GCTTGCGCAA CACCCAACAA 480 CTTACAAGTA TCATCGCCAC TCATGATCCT ATTGTCTTAG ATAGTTGCGA ATGGGTATTG 540

127

CTCCTTAAGA ATGGCAACAT TGCTCAATAC AAACCTTTAA ATTCTATATT AAAATCTGTA 600 GCTAAAACTT TTAACTTTAA AGAAAAACCA ACCACAAAAG ACTTATTAGC GTTACTAAAG 660 GATATTTAA 669 (2) SEQ ID NO. No. 27:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 1221 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 ... 1221 (xi) SEQUENCE DESCRIPTION: SEQ. No. 27:

ATGTATGCGG CTCATCCTAT TAAACCCATA AAAGCCCCTA AACTCAAATC TCAATTTTTA 60 AGGCGTGTGT TTGTGGGCGC GTCCATTAGG CGCTGGAATG ACCAAGCATG CCCTTTGGAA 120 TTTGTGGAAT TAGACAAGCA AGCCCATAAA GCGATGATTG CGTATCTGCT CGCTAAAGAT 180 TTAAAAGATA GGGGTAAAGA TTTAGATTTA GATCTTTTAA TCAAATATTT TTGCTTTGAG 240 TTTTTGGAGC GCTTGGTTTT AACCGATATT AAACCCCCTA.TTTTTTACGC CCTCCAACAA 300 ACGCATAGTA AAGAGTTAGC TTCCTATGTT GCQPAAAGTT TGCAAGATGA AATCAGTGCG 360 TATTTTTCTT TAGAGGAACT CAAAGAGTAT TTAAGCCACA GGCCTCAAAT TTTAGAAACT 420 CAAATTTTAG AGAGCGCGCA TTTTTATGCG TCTAAGTGGG .AGTTTGATAT TATCTATCAT 4 80 TTTAACCCCA ACATGTATGG CGTGAAAGAG ATTAAAGATA AAATTGACAA GCAACTCCAC 540 AATAACGATC ATTTGTTTGA AGGGCTTTTT GGGGAAAAAG AAGATTTGAA AAAATTGGTG 600 AGCATGTTTG GGCAGTTGCG TTTCCAAAAG CGCTGGAGCC AAACCCCAAG AGTGCCACAA 660 ACCAGTGTTC TAGGGCATAC TTTATGCGTG GCGATTATGG GGTATTTATT GAGTTTTGAC 720 TTGAAAGCTT GTAAAAGCAT GCGGATCAAT CATTTTTTGG GCGGGCTTTT CCATGATTTA 780 CCCGAAATTT TAACCCGAGA CATTATCACG CCCATCAAAC AAAGCGTTGC AGGGCTTGAT 840 CATTGCATTA AAGAGATT GA AAAAAAGGAA ATGCAAAACA AAGTCTATTC CTTTGTGTCT 900 TTGGGCGTTC AAGAAGATTT GAAATATTTC ACCGAAAACG AGTTTAAAAA CCGCTACAAA 960 GACAAGTCTC ATCAAATCGT TTTCACTAAA GACGCTGAAG AATTATTCAC GCTTTATAAT 1020 AGCGATGAAT ATCTTGGGGT TTGCGGGGAG CTTTTGAAGG TGTGCGATCA TTTGAGCGCG 1080 TTTTTAGAAG CCCAAATCTC TCTTTCTCAT GGCATTTCTA GCTACGATTT AATCCAAGGA 1140 GCTAAAAACC TTTTAGAATT GCGATCCCAA ACGGAACTGC TTGATTTGGA TTTAGGGAAA 1200 TTGTTTAGAG ATTTTAAGTA A 1221 (2) INFORMATION SEQ. No. 28:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 1008 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

128 (ix) SIGN:

(A) NAME / KEY: various characters (B) LOCATION 1 ... 1008 (xi) SEQUENCE DESCRIPTION: SEQ. No. 28:

GTGTTGTGGG TGCTATATTT TTTAACCAGT ΤΤΑΤΤΤΛΤΤΤ GCTCTTTGAT TGTTTTGTGG 60 TCTAAAAAAT CCATGCTCTT TGTGGATAAC GCTAATAAAA TCCAAGGCTT CCATCATGCA 120 AGAACCCCAC GAGCCGGGGG GCTTGGGATC TTTCTTTCTT TTGCGTTGGC TTGTTATCTT 180 GAACCTTTTG AGATGCCTTT TAAGGGGCCT TTTGTTTTCT TAGGGCTATC GCTAGTGTTT 240 TTGAGCGGTT TTTTAGAAGA CATTAACCTT TCATTAAGCC CCAAAATACG CCTTATTTTG 300 CAAGCTGTAG GGGTCGTTTG CATCATTTCA TCAACGCCTT TAGTGGTGAG CGATTTTTCG 360 CCCCTTTTTA GCTTGCCTTA TTTCATCGCT TTTTTATTCG CTATTTTTAT GCTGGTGGGT 420 ATCAGTAACG CTATTAATAT CATTGACGGG TTTÄACGGGC TTGCATCTGG GATTTGCGCG 480 ATCGCGCTTT TAGTCATTCA TTATATAGAC CCTAGCAGTT TGTCTTGTTT GCTCGCTTAC 540 ATGGTGCTTG GGTTTATGGT GTTAAATTTC CCTTCAGGAA AGATTTTTTT AGGCGATGGG 600 GGGGCGTATT TTTTGGGTTT GGTGTGCGGG ATTTCTCTCT TGCATTTGAG TTTGGAGCAA 660 AAAATCAGCG TGTTTTTTGG GCTCAATTTA ATGCTTTATC CGGTCATAGA GGTGCTTTTT 720 AGTATCCTTA GGCGCAAAAT AAAACGCCAG AAAGCCAl'CA TGCCGGATAA TTTGCATTTG 780 CACACCCTTT TATTTAAATT CTTGCAACAA CGCTCTTTCA ATTACCCTAA CCCTTTATGC 840 GCGTTTATC C TTATTCTATG CAACCTGCCT ΤΤΤΑΤΤΤΤΛΑ TAAGCGTTTT GTTTCGCTTG 900 GACGCTTATG CGCTCATTGT GATTAGCCTA GTCTTTATCG CATGCTATTT AATAGGCTAT 960 No. 29:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 291 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 ... 291

(xi) SEQUENCE DESCRIPTION: SEQ. No. 29:

ATGAAAAAGG TTATTGTGGC TTTAGGCGTT TTGGCGTTCG CAAATGTTTT AATGGCAACC 60 GATGTTAAGG CTCTTGTAAA AGGTTGTGCC GCTTGCCATG GGGTTAAGTT TGAAAAGAAA 120 GCTTTAGGTA AAAGCAAAAT CGTTAACATG ATGAGCGAAA AAGAGATTGA AGAGGATCTT 180 ATGGCTTTTA AAAGCGGTGC CAACAAGAAT CCTGTCATGA CCGCGCAAGC TAAAAAATTA 240 AGCGATGAAG ACATCAAAGC TTTAGCCAAA TACATCCCCA CTCTCAAATA and 291 (2) INFORMATION ON SEQ. No. 30:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 471 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

129

(See, ORIGINAL SOURCE: (A) ORGANISM: Helicobacter pylori (Ix, SIGN: (A) NAME / KEY: various characters (B, LOCATION 1 ... 471

(xi) SEQUENCE DESCRIPTION: SEQ. No. 30:

ATGCGAGATT TCAATAACAT TCAAATCACA CGCTTAAAAG TGCGTCAAAA TGCCGTTTTT 60 GAAAAACTGG ATCTGGAGTT TAAAGATGGC TTGAGCGCGA TTAGTGGGGC TAGTGGGGTG 120 GGGAAAAGCG TCCTTATTGC GAGCCTTTTA GGGGCGTTTG GGCTTAAAGA GAGCAACGCT 180 TCAAACATTG AAGTGGAATT GATCGCGCCT TTTTTAGACA CGGAAGAATA CGGCATTTTT 240 AGAGAAGATG AGCATGAACC CTTAGTTATT AGCGTGATTA AAAAAGAAAA AACACGCTAT 300 TTTTTAAACC AAACAAGCCT ATCTAAAAAC ACGCTCAAAG CGTTATTAAA GGGGCTTATT 360 AAACGCTTAT CTAACGACAG ATTCAGCCAG AATGAACTCA ACGATATTTT AATGCTCTCC 420 TTATTAGATG GCTATATCCA AAATAAAAAT AGGCGTTTAG CCCCCTTTTA G 471 (2) INFORMATION ABOUT SEQ. No. 31:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 357 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 ... 357 (xi) SEQUENCE DESCRIPTION: SEQ. No. 31:

GTGATGCTAA TGGCAATTTT TACCCCTTAT ATTCTTATTT TGAAAATGAT GAAAAAGTCT 60 ATGAGTTTAT TCGCCAATAT GGGGTTGGAG CAAATTTTTT GCAACAGAGA CATTAAAGAT 120 TTAAATGATT TTGTTTTTGG TATAGAAGTG GGGCTTGATA GCAATGCGAG AAAAAATCGT 180 AGCAGAAAGG CTATGGAAAA TCATCTTATC GGTCTTTTTG TCCAAGCTCA ATTAAATTTT 240 AAAGAACAAG TAGATATTAG AGAATTTGAG GATTTACGCC AGGCTTTTGG AAATGATACT 300 AAAAAATTTG ATTTTGTTAT TTTTAGCAAA GAGAAAACTT ATTTTCATAG AAGCTAA 357 (2) INFORMATION ON SEQ. No. 32:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 1068 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

130 (ix) SIGN:

(A) NAME / KEY: various characters (B) LOCATION 1 ... 1068 (xi) SEQUENCE DESCRIPTION: SEQ. No. 32:

ATGAATATCA AAATTTTAAA AATATTAGTT GGAGGGTTAT TTTTTTTGAG CTTGAACGCC 60 CATTTATGGG GGAAACAAGA CAATAGCTTT TTAGGGATTG GTGAAAGAGC CTATAAAAGC 120 GGGAATTATT CTAAAGCGGC GTCTTATTTT AAAAAAGCAT GCAACGATGG GGTGAGTGAA 180 GGCTGCACGC AATTAGGAAT CATTTATGAA AACGGGCAAG GCACTAGAAT AGATTATAAA 240 AAAGCCCTAG AATATTATAA AACCGCATGC CAGGCTGATG ATAGGGAAGG GTGTTTTGGC 300 TTAGGGGGGC TTTATGATGA GGGTTTAGGC ACGGCTCAAA ATTATCAAGA AGCCATTGAC 360 GCTTACGCTA AGGCATGCGT TTTAAAACAC CCTGAGAGTT GCTACAATTT AGGCATCATT 420 TATGATAGAA AAATCAAAGG CAATGCCGCT CAAGCGGTTA CTTACTATCA AAAAAGCTGT 480 AATTTTGATA TGGCTAAGGG GTGTTATATT TTAGGCACTG CCTATGAAAA AGGCTTTTTA 540 GAAGTCAAAC AGAGCAACCA TAAAGCCGTT ATCTATTATT TGAAAGCGTG CCGATTGAAT 600 GAGGGGCAGG CTTGCCGAGC GTTAGGGAGT TTGTTTGAAA ATGGCGATGC AGGGCTTGAT 660 GAAGATTTTG AAGTGGCGTT TGATTATTTG CAAAAAGCTT GCGCTTTAAA CAATTCTGGT 720 GGTTGCGCGA GTTTAGGCTC TATGTATATG TTGGGCAGGT ATGTTAAAAA AGACCCCCÄA 780 AAGGCTTTTA ACTATTTCAA GCAAGCATGC GATATGGGGA GCGCGGTGAG TTGCTCTAGG 840 ATGGGCTTTA TGTATTCGC A AGGGGACACT GTTTCAAAAG ACTTGAGGAA AGCCCTTGAT 900 AATTATGAAA GAGGTTGCGA TATGGGCGAT GAAGTGGGTT GCTTCGCTCT AGCGGGCATG 960 TATTACAACA TGAAAGATAA AGAAAACGCC ATAATGATTT ATGACAAGGG CTGTAAATTG 1020 GGCATGAAAC AGGCATGCGA AAATCTCACC AAACTCAGGG GGTATTAG 1068 (2) INFORMATION ON SEQ. NO.: 33:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 582 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 ... 582 (xi) SEQUENCE DESCRIPTION: SEQ. NO.: 33:

ATGAAAGAAA AAAACTTTTG GCCTTTAGGA ATCATGAGCG TGCTTATTTT TGGGCTTGGG 60 ATCGTGGTGT TTTTAGTGGT GTTTGCCCTA AAAAATTCGC CTAAAAATGA TTTAGTGTAT 120 TTCAAGGGTC ATAACGAAGT GGATTTAAAC TTTAACGCCA TGCTTAAAAC TTATGAAAAC 180 TTTAAATCCA ATTATCGTTT TTCAGTGGGT TTAAAGCCTC TTACCGAAAG CCCTAAAACC 240 CCCATTTTGC CCTATTTTTC TAAAGGCACG CATGGGGATA AAAAAATCCA AGAAAACCTT 300 TTAAACAACG CTTTGATTTT AGAAAAGTCC AACACGCTTT ATGCACAATT GCAACCGCTC 360 AAACCCGCTT TAGATTCGCC AAATATTCAA GTGTATTTAG CGTTCTATCC CAGCCAATCC 420 CAGCCCAGAT TATTAGGAAC GCTTGATTGT AAAAACGCAT GCGAACCTTT AAAATTTGAT 480 TTGTTAGAGG GCGATAAAGT GGGGCGCTAT AAGATCCTTT TTAAATTTGT TTTTAAAAAT 540 AAAGAAGAAT TGATTTTTGGA GCAACT.

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 870 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 ... 870 (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 34:

TTGGGTATCA ATATGTGTTC TAAAAAAATA AGAAATCTCA TTTTATGCTT TGGTTTTATT TTAAGCTTGT GCGCTGAAGA AAATATCACC AAAGAAAACA TGACTGAAAC GAACACGACT GAAGAAAACA CCCCTAAAGA CGCTCCCATT CTTTTGGAAG AAAAACGCGC CCAAACTCTA GAGCTTAAAG AAGAAAATGA AGTGGCAAAA AAGATTGATG AAAAAAGCCT GCTTGAAGAA ATCCATAAGA AAAAACGCCA GCTTTACATG CTCAAAGGGG AATTGCATGA AAAGAATGAA TCCATCTTAT TCCAACAAAT GGCTAAAAAT AAGAGCGGCT TTTTTATAGG CGTGATCCTT GGCGATATAG GGATTAACGC TAATCCTTAT GAGAAGTTTG AACTTTTAAG CAATATTCAA GCTTCTCCCT TGCTGTATGG TTTAAGGAGC GGGTATCAAA AGTATTTCGC TAACGGGATT AGCGCCTTAC GCTTTTATGG GGAATATTTA GGGGGGGCGA TGAAAGGGTT TAAAAGCGAT TCTTTAGCTT CTTATCAAAC CGCAAGCTTG AATATTGATC TGTTGATGGA TAAGCCTATT GACAAAGAAA AAAGGTTTGC GTTAGGGATA TTTGGAGGCG TTGGAGTGGG GTGGAATGGG ATGTATCAAA ATTTAAAAGA GATTAGAGGG TATTCACAGC CTAACGCCTT TGGGTTGGTG TTAAATTTAG GGGTGAGCAT GACGCTCAAC CTCAAACACC GCTTTGAATT AGCCCTAAAA ATGCCTCCCT TAAAAGAAAC TTCGCAAACC TTTTTATATT ATTTTAAAAG CACTAATATT TATTATATTA GTTACAACTA TTTATTGTAA (2, INFORMATION SEQ. NO.: 35:

(i, SEQUENCE CHARACTERISTICS:

(A) LENGTH: 2007 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 ... 2007 (xi, SEQUENCE DESCRIPTION: SEQ ID NO: 35:

ATGAGAAAAC TATTCATCCC ACTTTTATTA TTCAGCGCTT TAGAAGCGAA CGAGAAAAAC GGCTTTTTCA TAGAAGCCGG CTTTGAAACT GGGCTATTAG AAGGCACACA AACGCAAGAA AAAAGACACA CCACCACAAA AAACACTTAC GCAACTTACA ATTATTTACC CACAGACACG ATTTTAAAAA GAGCGGCTAA TTTATTCACC AATGCCGAAG CGATTTCAAA ATTAAAATTC TCATCTTTAT CCCCTGTTAG AGTGTTGTAT ATGTATAATG GTCAATTAAC TATAGAAAAC TTCTTGCCTT ATAATTTAAA TAATGTTAAG CTTAGTTTTA CAGACGCTCA AGGCAACACG ATTGATCTAG GCGTGATAGA GACCATCCCC AAACACTCTA AGATTGTTTT ACCCGGGGAG GCGTTTGATA GTTTAAAAGA GGCGTTTGAT AAAATTGACC CCTATACTTT ATTTCTTCCA AAATTTGAAG CCACTAGCAC TTCTATTTCT GATACTAACA CGCAGAGGGT GTTTGAAACG CTCAATAACA TTAAAACAAA TCTTATAATG AAATATAGTA ATGAAAATCC AAACAATTTC AACACTTGTC CTTACAATAA TAATGGTAAT ACAAAAAATG ATTGTTGGCCA

120

180

240

300

360

420

480

540

600

660

720

780

840

870

120

180

240

300

360

420

480

540

600

660

132

CCACÄAACCG CAGAAGAATT CACCAATTTA ATGTTGAACA TGATCGCTGT CTTAGACTCC 720

CAATCTTGGG GCGATGCGAT CTTAAACGCT CCTTTTGAAT TCACTAACAG CTCAACAGAT 780

TGCGATAGCG ATCCTTCAAA ATGCGTAAAT CCCGGAGTAA ATGGGCGTGT TGATACTAAA 840

GTCGATCAAC AATATATACT CAACAÄACAA GGTATTATTA ATAATTTTAG AAAAAAAATA 900

GAAATTGATG CGGTTGTTTT AAAAAATTCA GGGGTTGTAG GGTTAGCCAA TGGATATGGC 960

AATGATGGTG AATATGGCAC ATTAGGGGTA GAAGCCTATG CTTTAGATCC TAAAAAACTC 1020

TTTGGCAACG ACCTTAAGAC TATCAATTTA GAAGATTTAA GAACCATCTT GCATGAATTC 1080

AGCCACACTA AAGGCTATGG GCATAACGGG AATATGACCT ATCAAAGAGT GCCGGTAACG 1140

AAAGATGGTC AAGTGGAAAA GGATAGTAAT GGCAAGCCAA AAGATTCTGA TGGCCTCCCC 1200

TATAATGTGT GTTCGCTTTA TGGGGGATCC AATCAGCCCG CTTTCCCTAG CAACTACCCT 1260

AATTCCATCT ATCACAATTG TGCGGATGTC CCGGCTGC.CT TTTTAGGGGT AACAGCAGCG 1320

GTTTGGCAGC AGCTCATCAA TCAAAACGCC TTGCCGATCA ACTACGCTAA CTTGGGGAGT 1380

CAAACAAACT ACAACCTAAA CGCTAGTTTA AACACGl'AAG ATTTAGCCAA TTCCATGCTC 1440

AGCACCATCC AAAAAACCTT TGTAACTTCT AGCGTTACCA ACCACCATTT TTCAAACGCA 1500

TCGCAAAGTT TTÄGAAGCCC TATTTTAGGG GTTAACfJCTA AAATAGGCTA TCAAAACTAC 1560

TTTAATGATT TCATAGGGTT GGCTTATTAT GGCATCATCA AATACAATTA CGCTAAAGCT 1620

GTTAATCAAA AAGTCCAGCA ATTGAGCTAT GGTGGGGC.GA TAGATTTGTT ATTGGATTTC 1680

ATCACCACTT ACTCCAATAA AAATAGCCCT ACAGGCAT'IC AAACCAAAAG GAATTTTTCT 1740

TCATCTTTTG GTATCTTTGG GGGGTTAAGG GGCTTGTATA ACAGCTATTA TGTGTTGAAC 1600

AAAGTCAAAG GAAGCGGCAA TTTAGATGTG GCTACCGGGT TGAACTACCG CTATAAGCAT 1860

TCTAAATATT CTGTAGGGAT TAGCATCCCT TTAATCCAAA GAAAAGCTAG CGTCGTTTCT 1920

AGCGGTGGCG ATTATACGAA CTCTTTTGTT TTCAATGAAG GGGCTAGCCA CTTTAAGGTG 1980

TTTTTCAATT ACGGGTGGGT GTTTTAG 2007 (2) SEQ ID NO. No. 36:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 192 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 ... 192 (xi) SEQUENCE DESCRIPTION: SEQ. No. 36:

ATGAATACAG AAATTTTAA CATCATGTTA GTTGTCTCCG TGCTTATGGG ATTGGTAGGC 60 TTAATAGCGT TTTTATGGGG GGTTAAAAGC No. 37:

(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 : NOT

133 (vi, ORIGINAL SOURCE:

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

(A) NAME / KEY: various characters (B) LOCATION 1 ... 1221 (xi, SEQUENCE DESCRIPTION: SEQ ID NO: 37:

ATGGTATTTT TTCATAAGAA AATTATTTTA AATTTTATCT ATTCTTTAAT GGTTGCTTTT TTATTCCATT TATCCTATGG GGTTCTTTTA AAAGCCGATG GAATGGCTAA AAAGCAAACT CTTTTAGTGG GTGAAAGGCT TGTGTGGGAT AAGCTCACGC TGTTAGGGTT TTTAGAAAAA AACCATATCC CCCAAAAACT CTACTACAAT TTGAGCTCTC AAGATAAAGA ATTGAGTGCT GAAATCCAAA GCAATGTTAC CTACTACACT TTAAGAGATG CAAATAACAC GCTCATTCAA GCCCTTATCC CTATTAGCCA GGATTTGCAA ATCCATATTT ACAAAAAAGG AGAGGATTAT TTTTTAGACT TTATCCCCAT TGTTTTCACT CGTAAAGAAA GAACCCTCCT TCTTTCCTTA CAAACTTCGC CCTATCAAGA TATTGTCAAA GCCACCAATG ACCCCCTTTT AC-CCAACCAA TTGATGAACG CGTATAAAAA AAGCGTGCCT TTTAAACGCC TAGTGAAAAA CGATAAAATC GCTATCGTTT ATACAAGGGA TTATCGTGTG GGGCAAGCGT TTGGCCAGCC GACCATCAAA ATGGCGATGG TTAGCTCTCG TTTGCACCAA TACTATCTTT TTTCCCATTC AAACGGGCGT TATTACGATT CAAAAGCGCA AGAAGTGGCA GGGTTTTTAC TAGAAACCCC GGTGAAATAC ACCCGCATTT CTTCGCCTTT TTCGTATGGG AGGTTCCATC CTGTTTTAAA AGTTAAACGG CCTCATTACG GCGTGGATTA TGCGGCTAAA CATGGCAGTT TGATCCATTC TGCTTCAGAC GGCCGTGTGG GTTTTATAGG GGTTAAGGCG GGTTATGGGA AGGTGGTTGA AATCCATTTG AATGAATTG C GCTTGGTGTA TGCTCACATG AGCGCGTTCG CTAACGGATT AAAAAAAGGC TCGTTCGTTA AAAAAGGGCA AATCATAGGA AGAGTGGGAA GCACGGGTTT AAGCACCGGG CCGCATTTGC ATTTTGGCGT GTATAAAAAC TCCCGCCCCA TTAATCCTTT AGGCTATATC CGCACCGCTA AAAGCAAGCT GCATGGCAAA CAAAGAGAGG TTTTTTTAGA AAAAGCTCAG TATTCTAAGC AAAAATTAGA AGAACTTTTT AAAACCCATT CTTTTGAAAA AAATTCATTT TATCTTTTAG AGGGTTTTTA and (2) INFORMATION ON SEQ. No. 38:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 891 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: various characters (B) LOCATION 1 ... 891 (xi) SEQUENCE DESCRIPTION: SEQ. No. 38:

TTGTTTTTAG TCAAAAAAAT AGGCGTGGTA ATAATGATTT TAGTCTGCTT TTTAGCTTGC TCGCAAGAGA GCTTTATCAA AATGCAAAAA AAAGCCCAAG AGCAAGAAAA TGACGGCTCT AAACGCCCCA GCTATGTGGA TTCGGATTAT GAAGTCTTTA GCGAAACGAT TTTTTTACAA AACATGGTGT ATCAGCCTAT AGAGGAAAGA AACGCTTTTT TCCAACTGAC TAAAGATGAA GACAATTCTT TTAACCCTGA AAATTCCGTG ATTTTACTGA ATGAGCCAAG CGATAATAGT GAAAAAAACC TACTCTCATA CCCAAACGAT CCCAATAACA ATGAAGACAA CGCTAATAAT AGTCAAAAAA ATCCGTTCCT TTACAAGCCC AAAAGAAAAA CAAAAAACCC AAAACTCATT GAATATTCCC AACAAGATTT CTACCCCCTA AAAAATGGGG ATATTATCAT GAGTAAAGAA GGGGATCAAT GGTTGATAGA AATCCAATCC AAAGCCTTGA AGCGTTTTTT AAAAGATCAA ÄACGATAAAG ATCGCCAGAT CCAAACTTTC ACTTTTAATG ACACTAAAAC GCAAATCGCG CAAATTAAGG GCAAAATTTC TTCGTATGTT TATACCACCA ATAACGGTAG CTTGAGTTTA AGGCCTTTTT ATGAATCGTT TTTGTTAGAA AAAAAGAGCG ATAATGTTTA TACGATAGAG

120

180

240

300

360

420

480

540

600

660

720

780

840

900

960

1020

1080

1140

1200

1221

120

180

240

300

360

420

480

540

600

660

720

134

AATÄAGGCTT TAGATACTAT GGAGATTTCA AAGTGTCAAA TGGTGTTAAA AAAGCATTCA 780

ACCGATAAAT TAGACAGCCA GCATAAAGCC ATCAGTATTG ATTTGGATTT TAAAAAAGAG 840

CGCTTTAAGA GCGATACGGA ACTCTTTTTA GAATGTCTTA AGGAAAGTTA G 891 (2) INFORMATION ABOUT SEQ. No. 39:

(i) SEQUENCE CHARACTERISTICS:

(Ά) LENGTH: 747 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 ... 747 (xi) SEQUENCE DESCRIPTION: SEQ. No. 39:

GTGAGCTATG ACAACACCGA TGATTATTAT TTCCCTAGAA ATGGGGTTAT CTTTAGTTCC 60 TATGCGACAA TGTCTGGTTT GCCAAGCTCT GGCACGCTCA ATTCTTGGAA CGGGTTAGGC 120 GGGAATGTCC GTAACACCAA AGTTTATGGT AAATTCGCCG CTTACCACCA TTTGCAAAAA 180 TATTTATTGA TAGATTTGAT CGCTCGTTTT ÄÄAACGCAAG GGGGCTATAT CTTTAGGTAT 240 AACACCGATG ATTACTTGCC CTTAAACTCC ACTTTCTACA TGGGGGGCGT AACCACGGTG 300 AGAGGCTTTA GGAACGGCTC AATCACACCT AAAGATGAGT TTGGCTTGTG GCTTGGAGGC 360 GATGGGATTT TTACCGCTTC TACTGAATTG AGCTATGGGG TGTTAAAAGC GGCTAAAATG 420 CGTTTAGCGT GGTTTTTTGA CTTTGGTTTC TTAACCTTTA AAACCCCAAC TAGGGGGAGT 480 TTCTTCTATA ACGCTCCCAC CACGACGGCG AÄTTTTAAAG ATTATGGCGT TGTAGGGGCT 540 GGGTTTGAAA GGGCGACTTG GAGGGCTTCT ACAGGCTTAC AGATTGAATG GATTTCGCCC 600 ATGGGGCCTT TGGTGTTGAT TTTCCCTATA GCGTTTTTCA ACCAATGGGG CGATGGCAAT 660 GGCAAAAAAT GTAAAGGGCT GTGCTTTAAC CCTAACATGA ACGATTACAC GCAACATTTT 720 GAATTTTCTA TGGGAACAAG GTTTTAA 747 (2) INFORMATION ON SEQ. No. 40:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 1008 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 ... 1008 (xi) SEQUENCE DESCRIPTION: SEQ. No. 40:

GTGCAACACT TCAATTTCCT CTATAAAGAT TCTTTATTTT CTATCGCTTT ATTCACTTTC 60 ATTATCGCTC TTGTGATTTT ATTAGAACAG GCTAGAGCGT ATTTCACCCG AAAGAGAAAC 120

135

AAAAAATTTT TGCAAAAATT CGCCCAAAAT CAAAACGCCT ATGCGAGCAG CGAGAATTTA 180 GACGAGCTTT TAAAGCATGC TAAAATTTCC AGTTTGATGT TTTTAGCTAG GGCGTATTCT 240 AAAGCGGATG TGGAAATGAG CATTGAAATC TTAAAAGGGC TTTTGAATCG CCCCTTAAAA 300 GATGAAGAAA AAATCGCTGT TTTAGATTTA TTGGCTAAAA ATTATTTTAG CGTGGGGTAT 360 TTGCAGAAAA CAAAAGACAC CGTGAAAGAA ATTTTGCGCT TTTCCCCAAG GAATGTGGAA 420 GCGTTGTTGA AGCTTTTGCA TGCGTATGAA TTAGAAAAAG ATTATTCAAA GGCTTTAGAA 480 ACTTTGGAAT GTTTGGAAGA ATTAGAGGTG CCTAAAATTG AAACGATTAA AAATTACCTC 540 TATTTAATGC ATTTAATAGA GAATAAGGAA GATGCGGCTA AAATCTTGCA TGTTTCAAAA 600 GCGTCGTTAG ATTTGAAAAA AATCGCTCTG AATCACTTAA AATCGCATGA TGAAAATCTT 660 TTTTGGCAAG AAATTGATAC AACCGAACGG CTAGAAAATG TGATCGATCT TTTATGGGAT 720 ATGAATATCC CTGCTTTTAT TTTAGAAAAA CATGCCCTTT TGCAGGACAT CGCGCGATCT 780 CAAGGGTTGC TTTTGGATCA CAAACCTTGC CAAATTTTTG AATTAGAGGT TTTACGCGCT 840 CTATTGCATA GCCCTATAAA AGCGAGTCTG ACTTTTGAAT ACCGCTGCAA GCATTGCAAA 900 CAAATCTTTC CTTTTGAAAG CCATAGGTGT CCTGTGTGTT ACCAGTTAGC GTTTATGGAT 960 ATGGTGCTTA AAATCTCTA A AAAAACGCAT GCTATGGGAG TGGATTAA 1008 (2) INFORMATION ABOUT SEQ. No. 41:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 1242 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 ... 1242 (xi) SEQUENCE DESCRIPTION: SEQ. No. 41:

ATGAGGAAAA TTTTTTCTTA TATTTCTAAG GTTCTATTAT TTATTGGGGT GGTTTATGCA 60 GAGCCTGATT CTAAAGTGGA AGCCTTAGAA GGGAGGAAGC AAGAGTCTTC TTTGGATAAA 120 AAAATCCGCC AAGAATTGAA GAGTAAGGAA TTGAAGAATA AGGAATTAAA GAATAAGGAT 180 TTGAAAAATA AAGAAGAAAA GAAAGAAACA AAAGCCAAGA GAAAACCCAG AGCAGAAGTC 240 CATCATGGGG ACGCCAAAAA TCCCACTCCA AAGATCACGC CTCCTAAAAT CAAAGGGAGT 300 AGTAAGGGCG TTCAAAATCA AGGCGTTCAA AACAACGCGC CAAAACCTGA AGAAAAAGAT 360 ACAACCCCTC AAGCTACTGA AAAAAATAAG GAAACAAGCC CTAGCTCTCA ATTCAATTCC 420 ATTTTTGGTA ATCCTAATAA CGCTACCAAC AACACCCTTG AAGATAAGGT CGTAGGGGGC 480 ATTTCATTGC TTGTTAATGG TTCGCCTATC ACGCTGTATC AAATCCAAGA AGAGCAAGAA 540 AAATCTAAAG TGAGTAAGGC TCAAGCTAGG GATCGTTTGA TCGCTGAACG CATTAAAAAC 600 CAAGAAATTG AGCGCTTAAA AATCCATGTA GATGATGACA AGCTAGACCA AGAAATGGCG 660 ATGATGGCGC AACAACAAGG CATGGATTTA GACCATTTCA AACAGATGCT TATGGCTGAG 720 GGGCATTATA AACTCTATÄG AGATCAACTT AAAGAGCATT TAGAAATGCA AGAATTGTTG 780 CGTAATATTT TGCTCACGAA TGTGGATACC AGCTCTGAAA CCAAAATGCG CGAATATTAC 840 AACAAACACA AGGAGCAAT T CAGTATCCCC ACAGAAATAG AAACCGTGCG CTACACTTCC 900 ACCAATCAAG AGGATTTAGA AAGGGCTATG GCAGACCCTA ATTTGGAAGT CCCAGGGGTG 960 AGTAAGGCCA ATGAAAAAAT AGAGATGAAA ACCCTAAACC CTCAAATCGC CCAAGTCTTT 1020 ATTTCGCATG AGCAAGGCTC TTTCACGCCC GTTATGAATG GGGGTGGGGG GCAGTTCATC 1080 ACCTTTTATA TCAAGGAAAA AAGGGGTAAA AATGAAGTGA GCTTCAGTCA GGCCAAGCAA 1140 TTCATCGCCC AAAAATTAGT GGAAGAATCT AAGGATAAGA TTTTAGAAGA GCATTTTGAA 1200 AAATTGCGCG TTAAGTCTAG GATTGTGATG ATCAGAGAGT GA 1242 (2) SEQ ID NO. No. 42:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 561 base pairs (B) TYPE: nucleic acid

136

(C) NUMBER OF FIBERS: two (D) TOPOLOGY: round (Ii) MOLECULA TYPE: DNA (genomic) (Iii) HYPOTHETICAL: NO (Iv) ANTI-SENSE: NO (Vi) ORIGINAL SOURCE: (A) ORGANISM: Helicobacter (Ix) SIGN: (A) NAME / KEY: different characters (B) LOCATION 1 ... 561 (Xi) SEQUENCE DESCRIPTION: SEQ. No. 42:

ATGATTAAAA GAATTGCTTG TATTTTAAGC TTGAGCGCGA GTTTAGCGTT AGCTGGCGAA 60 GTGAATGGGT TTTTCATGGG TGCGGGTTAT CAACAAGGTC GTTATGGCCC TTATAACAGC 120 AATTACTCTG ATTGGCGTCA TGGCAATGAC CTTTATGGTT TGAATTTCAA ATTAGGTTTT 180 GTAGGCTTTG CCAATAAATG GTTTGGGGCT AGGGTGTATG GCTTTTTAGA TTGGTTTAAC 240 ACTTCAGGGA CTGAACACAC CAAAACCAAT TTGCTCACCT ATGGCGGCGG TGGCGATTTG 300 ATTGTCAATC TCATTCCTTT GGATAAATTC GCTCTAGGTC TCATTGGTGG CGTTCAATTA 360 GCCGGAAACA CTTGGATGTT CCCTTATGAT GTCAATCAAA CCAGATTCCA GTTCTTATGG 420 AATTTAGGCG GAAGAATGCG TGTTGGGGAT CGCAGTGCUT TTGAAGCGGG CGTGAAATTC 480 CCTATGGTTA ATCAGGGTAG CAAAGATGTA GGGCTTATCC GCTACTATTC TTGGTATGTG 540 GATTATGTCT TCACTTVCT G 561 (2). No. 43:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 729 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 ... 729

(xi) SEQUENCE DESCRIPTION: SEQ. No. 43:

ATGAAAAAAT TTTTTTCTCA ATCTTTGTTA GCTCTTATTA TCTCTATGAA TGCGGTATCT 60 GGCATGGATG GTAATGGCGT TTTTTTAGGG GCGGGTTATT TGCAAGGACA GGCGCAAATG 120 CATGCGGATA TTAATTCTCA AAAACAAGCC ACCAACGCTA CGATCAAAGG CTTTGACGCG 180 CTCTTGGGGT ATCAATTTTT CTTTGAAAAA CACTTTGGCT TACGCCTTTA TGGGTTTTTT 240 GACTACGCTC ATGCCAATTC TATTAAGCTT AAAAACCCTA ACTATAATAG CGAAGCGGCG 300 CÄAGTGGCTA GTCAAATTCT TGGGAAACAA GAAATCAATC GTTTAACAAA CATTGCCGAT 360 CCCAGAACTT TTGAGCCGAA CATGCTCACT TATGGGGGGG CTATGGACGT GATGGTTAAT 420 GTCATCAATA ACGGCATCAT GAGTTTGGGG GCTTTTGGCG GGATACAATT GGCCGGCAAT 480 TCATGGCTTA TGGCGACACC GAGCTTTGAG GGCATTTTAG TGGAACAAGC CCTTGTGAGC 540 AAGAAAGCCA CTTCTTTCCA ATTTTTATTC AATGTGGGGG CTCGCTTAAG GATCTTAAAA 600 CATTCTAGCA TTGAAGCGGG CGTGAAATTC CCCATGCTAA AGAAAAACCC CTACATCACT 660 GCAAAAAATT TGGATATAGG GTTTAGGCGC GTGTATTCGT GGTATGTGAA TTACGTGTTC ACTTTCTAG 720 729

137 (2) INFORMATION ABOUT SEQ. No. 44:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 771 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 ... 771

(xi) SEQUENCE DESCRIPTION: SEQ. No. 44:

ATGGGATACG CAAGCAAATT AGCTTTAAAG ATTTGTTTGG TAGGTTTATG TTTATTTAGC ACCCTTGGTG CAGAACACCT TGAGCAAAAA GGGAATTATA TTTATAAGGG AGAGGAGGCT TATAATAATA AGGAATATGA GCGAGCGGCT TCTTTTTATA AGAGCGCTAT TAAAAATGGT GAGTCGCTTG CTTATATTCT TTTAGGGATC ATGTATGAAA ATGGTAGGGG TGTACCTAAA GATTACAAGA AAGCGGTTGA ATATTTCCAA AAAGCTGTTG ATAACGATAT ACCTAGAGGG TATAACAATT TGGGCGTGAT GTATAAAGAG GGTAAGGGAG TTCCTAAAGA TGAAAAGAAA GCGGTGGAAT ATTTTAGAAT AGCTACAGAG AAAGGTTATA CTAACGCTTA TATCAACTTA GGCATCATGT ATATGGAGGG CAGGGGAGTT CCAAGTAACT ATGCGAAAGC GACAGAATGT TTTAGAAAAG CGATGCATAA GGGCAATGTG GAAGCTTATA TTCTCCTAGG GGATATTTAT TATAGCGGGA ATGATCAATT GGGTATTGAG CCGGACAAAG ATAAGGCTGT TGTCTATTAT AAAATGGCGG CTGATGTGAG TTCTTCTAGA GCTTATGAAG GGTTGTCAGA GTCTTATCGG TATGGGTTAG GCGTGGAAAA AGATAAAAAA AAGGCTGAAG AATACATGCA AAAAGCATGC GATTTTGACA TTGATAAAAA TTGTAAGAAA AAGAACACTT CAAGCCGATA and (2) INFORMATION ON SEQ. No. 45:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 1974 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 ... 1974 (xi) SEQUENCE DESCRIPTION: SEQ. No. 45:

ATGAGAAAAC TATTCATCCC ACTTTTATTA TTCAGCGCTT TAGAAGCGAA CGAGAAAAAC GGCTTTTTCA TAGAAGCCGG CTTTGAAACT GGGCTATTAG AAGGCACACA AACGCAAGAA AAAAGACACA CCACCACAAA AAACACTTAC GCAACTTACA ATTATTTACC CACAGACACG ATTTTAAAAA GAGCGGCTAA TTTATTCACC AATGCCGAAG CGATTTCAAA ATTAAAATTC TCATCTTTAT CCCCTGTTAG AGTGTTGTAT ATGTATAATG GTCAATTAAC TATAGAAAAC TTCTTGCCTT ATAATTTAAA TAATGTTAAG CTTAGTTTTA CAGACGCTCA AGGCAATGTG

120

180

240

300

360

420

480

540

600

660

720

771

120

180

240

300

360

138

ATCGATCTAG GCGTGATAGA GACTATCCCC AAACACTCTA AGATTGTTTT GCCCGGAGAG 420 GCATTTGATA GTCTAAAAAT TGACCCCTAT ACTTTATTTC TTCCAAAAAT TGAAGCCACT 480 AGCACTTCTA TTTCTGACGC TAACACGCAG AGGGTGTTTG AAACGCTCAA TAAGATTAAG 540 ACAAATTTGG TCGTAAATTA TAGGAATGAA AACAAATTTA AAGATCACGA AAATCATTGG 600 GAAGCCTTTA CCCCACAAAC CGCAGAAGAA TTCACTAATT TAATGTTGAA CATGATCGCT 660 GTTTTAGACT CCCAATCTTG GGGCGATGCG ATCTTAAACG CTCCTTTTGA GTTCACTAAC 720 AGCCCAACAG ATTGCGATAA TGATCCTTCA AAATGCGTAA ATCCTGGGAC AAACGGGCTT 780 GTCAATTCTA AAGTCGATCA AAAATATGTG TTAAACAAAC AAGACATTGT CAATAAATTT 840 AAAAACAAAG CGGATCTTGA TGTAATTGTT TTAAAGGATT CAGGGGTTGT AGGGGCTTGGG 900

GCTTCTGCTT TAGATCCTAA AAAACTCTTT GGCGATAACC TTAAGACTAT CAATTTAGAG 1020

GATTTAAGAA CCATCTTGCA TGAATTCAGC CACACTAAAG GCTATGGGCA TAACGGGAAT 1080

ATGACCTATC AAAGAGTGCC GGTAACGAAA GATGGTCAAG TGGAAAAGGA TAGTAATGGC 1140

AAGCCAAAAG ATTCTGATGG CCTCCCCTAT AATGTGTCITT CGCTTTATGG GGGATCCAAT 1200

CAGCCCGCTT TCCCTAGCAA CTACCCTAAT TCCATCTATC ACAATTGTGC GGATGTCCCG 1260

GCTGGCTTTT TAGGGGTAAC AGCAGCGGTT TGGCAGCAGC TCATCAATCÄ AAACGCCTTG 1320

CCGATCAACT ACGCTAACTT GGGGAGTCAA ACAAACTACA ACCTAAACGC TAGTTTAAAC 1380

ACGCAAGATT TAGCCAATTC CATGCTCAGC ACCATCCAAA AAACCTTTGT AACTTCTAGC 1440

GTTACCAACC ACCATTTTTC AAACGCATCG CAAAGTTTTA GAAGCCCTAT TTTAGGGGTT 1500

AACGCTAAAA TAGGCTATCA AAACTACTTT AATGATTTCA TAGGGTTGGC TTATTATGGC 1560

ATCATCAAAT ACAATTACGC TAAAGCTGTT AATCAAAAAG TCCAGCAATT GAGCTATGGT 1620

GGGGGGATAG ATTTGTTATT GGATTTCATC ACCACTTACT CCAATAAAAA TAGCCCTACA 1680

GGCATTCAAA CCAAAAGGAA TTTTTCTTCA TCTTTTGGTA TCTTTGGGGG GTTAAGGGGC 1740

TTGTATAACA GCTATTATGT GTTGAACAAA GTCAAAGGAA GCGGCAATTT AGATGTGGCT 1800

ACCGGGTTGA ACTACCGCTA TAAGCATTCT AAATATTCTG TAGGGATTAG CATCCCTTTA 1860

ATCCAAAGAA AAGCTAGCGT CGTTTCTAGC GGTGGCGATT ATACGAACTC TTTTGTTTTC 1920

AATGAAGGGG CTAGCCACTT TAAGGTGTTT TTCAATTACG GGTGGGTGTT TTAG 1974 (2) INFORMATION ABOUT SEQ. No. 46:

(1) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 504 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 ... 504 (xi, SEQUENCE DESCRIPTION: SEQ ID NO: 46:

ATGAAATTGG TGAGTCTTAT TGTAGCGTTA GTTTTTTGTT GTTTTTTAGG GGCTGTAGAG 60 TTGCCTGGAG TTTATCAAAC TCAAGAATTT TTATACATGA AAAGCTCTTT TGTGGAGTTT 120 TTTGAGCATA ACGGGAAGTT CTATGCCTAT GGTATTTCTG ATGTGGATGG CTCTAAAGCC 180 AAAAAAGACA ÄACTCAATCC TAACCCAAAG CTAAGGAATC GCAGCGATAA AGGCGTGGTG 240 TTTTTAAGCG ATTTGATTAA GGTTGGGGAA CAATCTTATA AAGGCGGTAA GGCGTATAAT 300 TTTTATGACG GCAAGACCTA CCATGTGAGA GTCACTCAAA ATTCAAACGG GGATTTGGAA 360 TTCACTTCAA GCTATGACAA ATGGGGGTAT GTGGGCAAAA CCTTCACCTG GAAACGCCTG 420 AGCGATGAAG AAATCAAAAA TCTAAAGCTC AAGCGTTTTA ACTTGGACGA AGTCCTTAAA 480 ACCCTCAAAG ATAGCCCTAT TTAA 504 (2, SEQ ID NO: 47:

(i, SEQUENCE CHARACTERISTICS:

(A, LENGTH: 885 base pairs (B, TYPE: nucleic acid)

139 (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. .885

(xi, SEQUENCE DESCRIPTION: SEQ ID NO: 47:

ATGAGTAATC AAGCGAGCCA TTTGGATAAT TTTATGAACG CTAAAAATCC CAAAAGTTTT TTTGATAATA AGGGGAATAC CAAATTCATC GCTATCACAA GCGGTAAGGG GGGCGTGGGG AAATCCAACA TTAGCGCTAA TTTAGCTTAC TCTTTATACA AGAAAGGTTA TAAGGTAGGG GTATTTGATG CGGATATTGG TTTAGCGAAT TTAGATGTCA TTTTTGGGGT GAAAACCCAT AAAAATATCT TGCATGCCTT AAAAGGCGAA GCCAAATTGC AAGAAATCAT TTGCGAGATT GAACCCGGGC TTTGCTTAAT CCCTGGGGAT AGCGGCGAAG AAATTTTAAA ATACATCAGC GGCGCGGAAG CTTTGGATCG ATTCGTAGAT GAAGAGGGGG TTTTAAGCTC TTTAGATTAT ATTGTGATTG ATACGGGTGC TGGGATTGGG GCCACTACGC AAGCGTTTTT GAATGCGAGC GATTGCGTGG TGATTGTTAC CACACCCGAT CCTTCAGCGA TTACCGATGC GTATGCATGC ATTAAAATCA ACTCCAAGAA TAAAGATGAA TTGTTCCTTA TCGCTAACAT GGTAGCCCAA CCTAAAGAAG GCAGGGCGAC TTATGAAAGG CTATTCAAGG TGGCTAAAAA CAATATCGCT TCATTAGAAT TGCACTATTT AGGGGCGATT GAAAACAGCT CCTTATTGAA ACGCTATGTG AGGGAGCGAA AGATTTTGAG GAAAATAGCC CCTAACGATT TGTTTTCGCA ATCCATTGAC CAGATAGCGA GCCTTTTAGT TTCTAAACTA GAAACCGGCA CTTTAGAAAT ACCAAAAGAA GGTTTAAAAA GCTTTTTTAA AAGGCTTTTG AAGTATTTGG GGTAG (2, INFORMATION SEQ. NO .: 48:

(i, SEQUENCE CHARACTERISTICS:

(A) LENGTH: 1119 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 ... 1119 (xi) SEQUENCE DESCRIPTION: SEQ. No. 48:

TTGGAACCTT CAAGAAATCG CCTAAAACAT GCCGCCTTTT TTGTGGGGCT TTTTATCGTT TTGTTTTTAA TTATAATGAA GCACCAAACC TCCCCCTATG CTTTCACGCA TAATCAAGCC CTTGTCACTC AAACCCCCCC CTATTTCACG CAACTCACTA TCCCTAAACC AAATGACGCT TTAAGCGCGC ATGCGAGCTC TTTAATCAGC TTGCCTAACG ACAATCTTTT GAGCGCTTAT TTTAGCGGCA CTAAAGAAGG GGCAAGGGAT GTGAAAATCA GCGCGAATCT TTTTGACAGC AAGACTAATC GCTGGAGCGA AGCCTTCATT CTTTTAACCA AAGAAGAGCT TTCTCATCAT TCGCATGAAT ACATCAAAAA ATTAGGTAAC CCCTTGCTTT TTTTGCATGA TAATAAAATT TTGTTGTTTG TCGTAGGGGT GAGCATGGGC GGGTGGGCCA CTTCTAAAAT CTATCAATTT GAAAGCGCTT TAGAGCCGAT TCATTTTAAG TTTGCGCGAA AACTCTCTTT AAGCCCTTTT

120

180

240

300

360

420

480

540

600

660

720

780

840

885

120

180

240

300

360

420

480

540

140

TTAAATTTGA GCCATTTAGT AAGGAATAAG CCTTTAAACA CCACTGATGG CGGGTTTATG 600

CTACCACTCT ATCACGAATT AGCCACCCAA TACCCCTTGT TGTTGAAATT TGACCAACAA 660

AATAACCCAA GAGAGCTTTT AAGGCCTAAT ACCTTAAACC ACCAGCTCCA ACCAAGCTTA 720

ACCCCCTTTA AAGACTGCGC TGTCATGGCG TTTAGAAACC ATTCTTTTAA AGATAGCCTC 780

ATGCTAGAAA CCTGTAAAAC CCCCACTGAT TGGCAAAAAC CCATTTCTAC AAATCTTAAA 840

AACTTAGATG ATTCTTTAAA TTTACTCAAT TTAAATCCAA TATTGTATTT GATCCACAAC 900

CCTAGCGATT TATCACTGCG TCGTAAAGAA CTTTGGCTTT CTAAATTAGA AAACTCCAAC 960

TCGTTTAAAA CCTTAAAAGT TTTGGATAAA GCGAATGAAG TGAGTTACCC AAGCTATAGC 1020

CTTAATCCGC ATTTTATAGA TATTGTCTAT ACTTACAACC GCTCTCATAT CAAACACATC 1080

CGTTTCAATA TGGCTTATTT AAATTCCCTT CTCAAGTGA 1119 (2) SEQ ID NO. No. 49:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 2937 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 ... 2937

(xi) SEQUENCE DESCRIPTION: SEQ. No. 49:

ATGAAGAAAA GAAAACATGT ATCCAAGAAA GTGTTTAATG TCATTATCTT GTTTGTGGCA 60 GTATTCACTC TTTTAGTCGT CATTCACAAA ACCCTTTCAA ACGGCATTCA CATACAAAAT 120 TTAAAAATTG GAAAACTTGG CATTTCTGAA TTATACTTAA AACTCAATAA CAAGCTTTCT 180 TTGGAAGTTG AGCGGGTTGA TCTCTCTTCT TTCTTCCATC AAAAACCCAC TAAAAAGCGT 240 TTAGAAGTTT CTGATTTGAT TAAAAATATC CGTTATGGCA TTTGGGCGGT GTCTTATTTT 300 GAAAAACTTA AAGTCAAAGA AATCATTTTA GACGATAAAA ATAAAGCCAA TATCTTTTTT 360 GATGGGAATA AATACGAGTT AGAATTTCCA GGAATCAAAG GGGAATTTTC CCTAGAAGAC 420 GATÄAAAATA TCAAGCTTAA AATCATCAAT TTGCTTTTTA AAGATGTTAA AGTCCAAGTG 480 GATGGCAACG CCCACTATTC ACCCAAAGCC AGGAAAATGG CGTTCAATTT GATTGTCAAG 540 CCCTTAGTTG AACCCAGCGC TGCAATTTAT TTGCAAGGGC TAACCGATTT AAAAACCATA 600 GAATTAAAAA TTAACACTTC TCCAATGAAA AGCCTAGCGT TTTTAAAGCC TCTTTTCCAA 660 CGCCAATCGC AAAAAAATTT AAAAACGTGG ATTTTTGACA AGATCCAATT TGCCAGCTTT 720 AAGATTGATA ACGCTTTAAT CAAGGCTAAT TTCACTCCTA GCGAGTTTAT CCCATCGCTT 780 TTGGAAAATT CTGTAGTTAA AGCCACTTTG ATTAAGCCTT CAGTCGTTTT TAATGATGGC 840 TTATCGCCCA TTAAAATGG A TAAAACCGAA TTGATTTTCA AAAACAAACA GCTCCTCATA 900 CAGCCCCAAA AAATCACTTA TGAAACCATG GAATTAACCG GCTCTTACGC CACTTTTTCC 960 AATTTGTTAG AAGCCCCTAA GTTGGAGGTT ΤΤΤΤΤΑΑΛΑΑ CGACCCCTAA TTATTATGGC 1020 GATAGCATTA AGGATTTATT GAGCGCTTAT AAAGTCGTTT TACCTTTGGA TAAAATCAGC 1080 ATGCCATCTA GCGCGGATTT GAAGCTCACT TTGCAATTCT TAAAAAACAC CGCCCCCTTA 1140 TTTAGCGTTC AAGGCAGCGT TAATTTGCAA GAAGGCACTT TCTCGCTCTA TAATATCCCC 1200 CTTTACACGC AAAGCGCTCA AATCAATTTG GACATCGCCC AAGAATACCA ATACATCTAC 1260 ATAGACACGA TCCACACGCG CTATGCAAAC ATGCTGGATT TAGACGCTAA AATCGCTTTA 1320 GATTTAGGTC AAAAAAACCT TTCTTTGGAT TCTTTAGTCC ATAAAATCCA AGTCAATACC 1380 AATAACÄATA TCAACATGCG CTCTTATGAT CCCAATAACA CTCAAGAAGA TCCGCAAACT 1440 AACTTTACTT TGGATCTAAA AAGCTTGCAT TCTATCATTC AAGAGGGTGA AAATTCAGAA 1500 GTTTTTAGAA GAAAAATCAT AGACACCATT AAAGCCCAAA GCGAAGATAA ATTCACTAAA 1560 GATGTTTTTT ACGCCACAGG AGACACTCTC AAAAGCCTGT CGTTGAGTTT TGATTTTTCC 1620 AACCCCGATC ACATACAATG GAGCGTGCCA CAACTCTTAT TAGAAGGCGA ATTTAAAGAT 1680 AACGCCTATA C TTT AGAT CAAAGATTTG AAAAAGATCA AGCCCTATTC CCCCATTATG 1740 GACTATATTG CCCTAAAAGA CGGCTCTTTA GAGGTTTCTA CGAGCGATTT TGTCAATATT 1800 GATTTTTTTG CTAAAGATTT GAAAATCAAC CTCCCCATTT ATAGGAGCGA TGGATCGCAT 1860 TTTGATTCTT TTTCTTTATT TGGCTCTATC AATAAAGATG AAATTTCTGT CTATACTCCA 1920

141

AGCAAAAGCA TATCCATAAA AGTTAAGGGG GATCAAAAGG ATATTACCCT TAATAACATT GATTTGAGTA TTGATGATTT CTTGGATAGT AAAATGCCAG CTATTGCGGG ATTATTCTCA AAAGAACGAA AAGAAAAGCC TAGCTCTAAA GAAATCCAAG ATGAAGATGT TTTCATTAGC GCCAAACAAC GCTATGAAAA AGCCCACAAA ATTATCCCCA TCTCTACACG CATCCATGCT AAAGATGTCG TGCTGATCTA TAAAAAAATG CCTTTTCCTT TAGAAAATCT TGATATTGTC GCTCAAGACG ATAGGGTGAA AATTGATGGC AATTATAAAA ACGCCATGAT CATGGCGGAT TTAGTGCATG GGGCTTTGTA TCTTAAGGCT CATAATTTTA GCGGGGATTA TATCAACACC ATTCTTCAAA AAGATTTCGT AGAAGGAGGC TTATTCACGC TTATTGGGGC TCTTGAAGAT CAGGTTTTCA ATGGCGAATT GAAATTCCAA AACACAAGCT TAAAGAATTT CGCCCTCATG CAAAACATGG TCAATCTCAT CAACACCATT CCCTCCCTCA TTGTCTTTAG AAACCCTCAT TTAGGGGCTA ATGGCTATCA AATCAAAACC GGCTCCGTTG TGTTTGGGAT CACTAAAGAA TATTTAGGGT TAGAAAAAAT TGATCTTGTC GGCAAAACGC TTGATATTGC TGGCAATGGA ATCATTGAAT TAGACAAAAA CAAATTAGAT TTAAACTTAG AAGTTTCCAC TATCAAGGCT TTGAGTAATG TCTTAAATAA AATCCCTATC GTGGGCTATC TCGTTTTAGG AAAAGGAGGT AAAATCACCA CTAACGTGAA TGTCAAAGGC ACGTTGGATA AGCCTAAAAC CCAAGTAACT TTAGCGTCAG ATATTATCCA AGCGCCTTTT AAAATCTTAC GCCGTATTTT CACGCCTATT GACATCATCG TGGATGAAGT CAAGAAAAAC ATTGATTCAA AAAGGAAATT AAAATGA (2) SEQ ID NO. No. 50:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 1434 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 ... 1434

(xi) SEQUENCE DESCRIPTION: SEQ. No. 50:

ATGAATACTA TTATAAGATA TGCGAGTTTA TGGGGCTTGT GTATTACTCT AACTCTAGCG CAAACCCCCT CTAAAACCCC TGATGAAATC AAGCAAATCC TTAACAATTA TAGCCATAAG AATTTAAAGC TCATTGATCC GCCGACAAGT TCTTTAGAAG CGACACCGGG TTTTTTACCC TCGCCTAAAG AAACAGCGAC CACGATCAAT CAAGAGATCG CTAAATACCA TGAAAAAAGC GATAAAGCCG CTTTGGGGCT TTATGAATTG CTAAAGGGGG CTACCACCAA TCTCAGTTTG CAAGCGCAAG AACTCAGTGT CAAGCAAGCG ATGÄAGAACC ACACCATCGC CAAAGCGATG TTTTTGCCTA CTTTGAACGC GAGTTATAAT TTTAAAAATG AAGCTAGGGA TACTCCAGAA TATAAGCATT ATAACACCCA ACAACTCCAA GCTCAAGTCA CATTGAATGT GTTTAATGGC TTTAGCAATG TGAATAATGT CAAAGAAAAG TCTGCGACTT ACCGATCCAC TGTGGCTAAT TTAGAATATA GCCGCCAAAG CGTGTATTTG CAAGTGGTGC AACAATACTA CGAGTATTTT AACAATCTCG CTCGCATGAT CGCTTTGCAA AAGAAATTAG AGCAAATCCA AACGGACATT AAAAGGGTTA CTAAGCTCTA TGACAAAGGG CTGACCACGA TTGATGATTT ACAAAGCTTA AAAGCGCAAG GGAATTTGAG CGAATACGAT ATTTTGGACA TGCAATTTGC TTTGGAGCAA AACCGCTTGA CTTTAGAATA CCTCACTAAC CTCAGTGTGA AAAATTTGAA AAAGACCACG ATTGATGCGC CTAATTTGCA ATTAAGAGAA AGGCAGGATT TGGTTTCTTT AAGGGAGCAG ATTTCTGCA C TCAGATACCA AAACAAGCAA CTCAATTATT ACCCCAAGAT AGATGTGTTT GACTCATGGC TTTTTTGGAT CCAÄAAACCC GCTTATGCCA CAGGGCGTTT TGGGAATTTC TACCCAGGTC AGCAAAATAC GGCTGGGGTT ACTGCGACTT TGAATATTTT TGATGATATA GGGTTGAGCT TGCAAAAACA ATCCATCATG CTAGGCCAAT TAGCGAATGA AAAGAATTTA GCGTATAAAA AATTGGAGCA AGAAAAAGAC GAACAGCTTT ACAGAAAGTC GCTTGATATT GCCAGAGCTA AGATTGAATC TTCAAAGGCT AGTTTGGATG CGGCCAATCT TTCTTTTGCC AATATTAAAA GGAAATACGA CGCTAATTTA GTGGATTTCA CTACCTATTT AAGGGGCTTA ACCACGCGCT TTGATGCAGA AGTGGCTTAC AATTTAGCGC TCAACAATTA CGAAGTGCAA AAAGCCAATT ACATTTTTAA CAGCGGGCAT AAAATAGACG ACTATGTGCA TTAA

1980

2040

2100

2160

2220

2280

2340

2400

2460

2520

2580

2640

2700

2760

2820

2880

2937

120

180

240

300

360

420

480

540

600

660

720

780

840

900

960

1020

1080

1140

1200

1260

1320

1380

1434

142 (2, SEQ ID NO: 51:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 1239 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 ... 1239 (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 51:

ATGCTATCTT TTATAAGCGC GTTTGATAAA AGGGGCGTTT CAATACGCCT TCTAACAGCC 60

TTGTTACTGC TTTTTAGTTT GGGTTTGGCT AAAGATTTAG AAATCCAAAC TTTTGTGGCT 120

AAATACCTTT CTAAAAATCA AAAAATACAA GCCCTACAGG AGCAAATTGA CGCTTTAGAT 180

TCTCAAGAAA AAGTCGTTAG CAAATGGGAT AACCCTATTT TGTATTTAGG CTATAACAAC 240

GCTAACGTGA GCGATTTTTT CAGGCTGGAT AGCACCTTAA TGCAAAACAT GAGCTTGGGT 300

TTGTCTCAAA AAGTGGATTT AAATGGTAAA AAACTCACGC AGTCTAAAAT GATCAATTTA 360

GAAAAACAAA AAAAAATATT AGAGCTTAAA AAAACCAAGC AGCAATTGGT GATTAATTTA 420

ATGATAAACG GCATTGAAAA CTATAAAAAC CAACAÄGAAA TAGAGCTTTT AAACACAGCG 480

ATTAAAAATT TAGAAAACAC CCTCTATCAA GCCAACCATT CCAGTTCGCC CGATTTAATA 540

GCGATCGCCA AGTTAGAAAT TTTAAAATCG CTATTAGAAA TCCAAAAAAA CGATTTAGAA 600

GTAGCGCTCT CTAGCAGCCA TTATTCCATG GGCGAATTGA CTTTTAAAGA AAACGAGATT 660

TTAAGCATTG CCCCTAAAAA TTTTGAATTC AATAACGAGC AAGAGCTGCA TAACATTAGC 720

GCCACTAATT ACGATATTGC GATCGCCAGG CTTGATGAAG AAAAAGCACA AAAAGACATC 780

ACTCTGGCTA AAAAAAGCTT TTTAGAAGAC ATAAACGTTA CCGGGGTGTA TTATTTCCGC 840

TCCAAACAAT ACTATAACTA CGACATGTTT AGCGTCGCTT TGTCTATCCC TTTACCTCTT 900

TATGGCAAGC AGGCTAAATT AGTGGAGCAA AAGAAAAAAG AAAGCTTGGC GTTTAAAAGC 960

GAAGTGGAAÄ ACGCCAAAAA CAAAACGCGC CACCTGGCCC TAAAACTCCT TAAAAAATTA 1020

GAAACCTTGC AAAAAAACCT GGAATCGATC AATAAAATCA TCAAACAGAA TGAAAAAATC 1080

GCGCAAATTT ATGCGCTTGA TTTGAAAACT AATGGCGATT ACAACGCTTA TTACAACGCC 1140

TTGAATGACA AAATCACTAT TCAAATCACC CAGCTTGAAA CCTTAAGCGC TCTAAATAGT 1200

GCTTATTTGT CCTTACAAAA TCTCAAAGGA TTAGAATGA 1239 (2) INFORMATION ABOUT SEQ. No. 52:

(i, SEQUENCE CHARACTERISTICS:

(A) LENGTH: 414 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 ... 414

143 (xi) SEQUENCE DESCRIPTION: SEQ. No. 52:

ATGCGTATAG TTAGAAATTT ATTTCTTGTA TCGTTTGTGG CGTATAGTAG TGCGTTCGCA 60 GCGGATTTAG AAACCGGAAC CAAAAACGAC AAAAAGAGCG GTAAAAAATT TTACAAACTC 120 CATAAAAACC ATGGCTCAGA AACCGAGACT AAAAACGATA AAAAGCTTTA TGATTTCACT 180 AAAÄATAGCG GATTAGAAGG CGTGGATTTA GAAAAAAGCC CTAACCTTAA AAGCCATAAA 240 AAAAGCGATA AAAAGTTTTA TAAACAACTC GCTAAAAACA ATATCGCTGA AGGGGTGAGC 300 ATGCCGATTG TGAATTTCAA TAAAGCCCTA TCTTTTGGGC CTTATTTTGA AAGGACTAAA 360 AGCAAAAAAA CCCAATACAT GGACGGCGGG TTGATGATGC ACATCCGTTT TTAA 414 ( 2) INFORMATION ON SEQ. No. 53:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 930 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 ... 930 (xi, SEQUENCE DESCRIPTION: SEQ ID NO: 53:

TTGATGCCAC AAAACCAGCT TGTGATCACC ATCATTGATG AATCAGGCTC TAAGCAACTC 60 AAATTTTCTA AAAATTTAAA ACGCAACCTC ATCATTTCTG TTGTCATTCT TTTATTGATC 120 GTGGGGCTTG GCGTGGGGTT TTTAAAATTT TTAATCGCTA AAATGGATAC GATGACAAGC 180 GAGAGGAATG CGGTTTTAAG GGATTTTAGG GGTTTGTATC AAAAAAATTA CGCCCTAGCG 240 AAAGAGATTA AAAACAAGCG AGAAGAGCTT TTTATTGTGG GGCAAAAGAT CCGTGGGCTA 300 GAATCCTTGA TTGAAATCAA AAAGGGGGCT AATGGGGGAG GGCATCTCTA TGATGAAGTG 360 GATTTAGAAA ATTTGAGCTT AAATCAAAAA CATTTAGCAC TCATGCTCAT TCCTAATGGC 420 ATGCCCCTAA AAACTTATAG CGCTATCAAA CCCACTAAAG AAAGGAACCA CCCCATTAAA 480 AAGATTAAGG GCGTTGÄATC CGGGATCGAT TTTATCGCGC CATTGAACAC GCCTGTGTAT 540 GCGAGCGCTG ATGGGATTGT GGATTTTGTG AAGACTCGTT CTAATGCGGG GTATGGGAAC 600 TTGGTGCGCA TTGAACATGC GTTTGGTTTC AGCTCCATTT ATACGCACTT AGATCATGTC 660 AATGTGCAGC CTAAAAGCTT CATCCAAAAA GGGCAGTTGA TTGGCTATAG CGGGAAGAGC 720 GGTAATAGCG GCGGCGAAAA ATTGCATTAT GAAGTGCGGT TTTTGGGTAA AATTTTAGAC 780 GCAGAAAAAT TCCTAGCATG GGATTTGGAT CATTTTCAAA GCGCTTTAGA AGAAAATAAA 840 TTTATTGAAT GGAAGAATC T GTTTTGGGTT TTAGAAGACA TCGTCCAGCT CCAAGAGCAT 900 GTGGATAAAG ACACCTTAAA AGGTCAGTAG 930 (2, SEQ ID NO. No. 54:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 999 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

144 (ix) SIGN:

(A) NAME / KEY: various characters (B) LOCATION 1 ... 999 (xi) SEQUENCE DESCRIPTION: SEQ. No. 54:

GTGCTATATT TTTTAACCAG TTTATTTATT TGCTCTTTGA TTGTTTTGTG GTCTAAAAAA 60 TCCATGCTCT TTGTGGATAA CGCTAATAAA ATCCAAGGGT TCCATCATGC AAGAACCCCA 120 CGAGCCGGGG GGCTTGGGAT CTTTCTTTCT TTTGCGTTCG CTTGTTATCT TGAACCTTTT 180 GAGATGCCTT TTAAGGGGCC TTTTGTTTTC TTAGGGCTAT CGCTAGTGTT TTTGAGCGGT 240 TTTTTAGAAG ACATTAACCT TTCATTAAGC CCCAAAATAC GCCTTATTTT GCAAGCTGTA 300 GGGGTCGTTT GCATCATTTC ATCAACGCCT TTAGTGG'ľCA GCGATTTTTC GCCCCTTTTT 360 AGCTTGCCTT ATTTCATCGC TTTTTTATTC GCTATTTTTA TGCTGGTGGG TATCAGTAAC 420 GCTATTAATA TCATTGACGG GTTTAACGGG CTTGCATCTG GGATTTGCGC GATCGCGCTT 480 TTAGTCATTC ATTATATAGA CCCTAGCAGT TTGTCTTCTT TGCTCGCTTA CATGGTGCTT 540 GGGTTTATGG TGTTAAATTT CCCTTCAGGA AAGATTTTTT TAGGCGATGG GGGGGCGTAT 600 TTTTTGGGTT TGGTGTGCGG GATTTCTCTC TTGCATTTGA GTTTGGAGCA AAAAATCAGC 660 GTGTTTTTTG GGCTCAATTT AATGCTTTAT CCGGTCATAG AGGTGCTTTT TAGTATCCTT 720 AGGCGCAAAA TAAAACGCCA GAAAGCCACC ATGCCGGATA ATTTGCATTT GCACACCCTT 780 TTATTTAAAT TCTTGCAACA ACGCTCTTTC AATTACCCTA ACCCTTTATG CGCGTTTATC 840 CTTATTCTAT GCAACCTG CC TTTTATTTTA ATAAGCGTTT TGTTTCGCTT GGACGCTTAT 900 GCGCTCATTG TGATTAGCCT AGTCTTTATC GCATGCTATT TAATAGGCTA TGCTTATTTG 960 AATAGGCAAG TTTGCGCTTT AGAAAAAGCGG INFO No. 55:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 816 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 ... 816 (xi, SEQUENCE DESCRIPTION: SEQ ..- 55:

ATGAACATAT TCAAGCGTAT TATTTGCGTA ACCGCTATTG TTTTAGGTTT TTTTAACCTT 60 TTAGACGCCA AACACCACAA AGAAAAAAAA GAAGACCACA AAATCACTCG TGAGCTTAAA 120 GTGGGCGCTA ACCCTGTGCC GCATGCGCAA ATCTTGCAAT CAGTTGTGGA TGATTTGAAA 180 GAGAAAGGGA TCAAATTAGT GATCGTGTCT TTTACGGATT ATGTGTTGCC TAATTTAGCG 240 CTCAATGACG GCTCTTTAGA CGCGAATTAC TTCCAGCACC GCCCTTATTT GGATCGGTTT 300 AATTTGGACA GAAAAATGCA CCTTGTTGGT TTGGCCAATA TCCATGTGGA GCCTTTAAGA 360 TTTTATTCTC AAAAAATCAC AGACATTAAA AACCTTAAAA AAGGCTCAGT GATTGCTGTG 420 CCAAATGATC CGGCCAATCA AGGCAGGGCG TTGATTTTAC TCCATAAACA AGGCCTTATC 480 GCTCTCAAAG ACCCAAGCAA TCTATACGCT ACGGAGTTTG ATATTGTCAA AAATCCTTAC 540 AACATCAAAA TCAAACCCCT AGAAGCTGCG TTATTGCCTA AGGTTTTAGG GGATGTGGAT 600 GGGGCTATCA TAACAGGGAA TTATGCCTTG CAAGCAAAAC TCACCGGAGC CTTATTTTCA 660 GAAGATAAGG ACTCGCCTTA TGCTAATCTT GTAGCCTCTC GTGAGGATAA TGCGCAAGAT 720 GAAGCGATAA AAGCGTTGAT TGAAGCCTTA CAGAGCGAAA AGACCAGGAA ATTCATTTTG 780 GATACCTATA AGGGGGCGAT TATCCCGGCT TTTTAA 816 (2, INFORMATION ABOUT NO: 56:

(i, SEQUENCE CHARACTERISTICS:

145 (A) LENGTH: 951 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 ... 951 (xi) SEQUENCE DESCRIPTION: SEQ. No .-. 56:

ATGCAAGAAT TCAGTTTGTG GTGCGATTTT ATAGAAAGGG ATTTTTTAGA AAACGATTTT TTAAAGCTCA TCAATAAGGG GGCTATTTGC GGGGCGACGA GTAACCCTAG TTTGTTTTGC GAAGCGATCA CAAAAAGCGC GTTTTATCAA GATGAAATCG CTAAACTCAA AGGCAAAAAA GCTAAAGAAA TTTATGAAAC TCTGGCACTA AAGGATATTT TACAAGCCTC TAGCGCGTTA ATGCCTTTGT ATGAAAAAGA CCCTAACAAC GGCTACATCA GCCTAGAAAT TGACCCCTTT TTAGAAGACG ATGCGATTAA AAGCATTGAT GAAGCCAAGC GGTTATTCAA AACATTAAAC CGCCCCAATG TGATGATTAA AGTCCCGGCG AGTGAAAGCG CTTTTGAAGT CATTAGCGCT CTGGCTCAAG CCTCTATCCC CATTAATGTA ACTTTAGTCT TTTCGCCTAA AATTGCCGGT GAAATCGCTC AAATCTTAGC CAAAGAAGCA CGAAAAAGAG CGGTCATTAG CGTGTTTGTC TCACGATTTG ACAAAGAAAT AGACCCACTA GTGCCACAAA ATTTGCAAGC TCAAAGTGGG ATCATGAACG CTACCGAGTG TTATTATCAA ATCAACCAGC ATGCTAATAA GCTAATAAGC ACCCTTTTTG CATCCACCGG CGTTAAATCT AATTCTTTAG CTAAAGATTA CTACATTAAA GCGCTGTGTT TTAAAAACTC TATCAACACA GCCCCCCTAG ACGCCCTAAA CGCTTATTTG CTTGACCCAA ACACCGAGTG TCAAACCCCT TTAAAAATCA CAGAAATTGA AGCGTTCAAA AAAGAATTAA AAACGCACAA TATTGATTTA GAAAACACCG CCCAAAAACT CCTTAAAGAA GGCTTGATAG CGTTCAAACA ATCCTTTGAA AAGCTTTTAA GCAGTTTTTG A (2) SEQ ID NO. No. 57:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 783 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 ... 783 (xi, SEQUENCE DESCRIPTION: SEQ ID NO: 57:

ATGAAAACAA ATGGTCATTT TAAGGATTTT GCATGGAAAA AATGCTTTTT AGGCGCGAGC GTGGTGGCTT TATTAGTGGG GTGTAGCCCG CATATTATTG AAACCAATGA AGTTGCTTTG AAATTGAATT ACCATCCAGC TAGCGAGAAA GTTCAAGCGT TAGATGAAAA GATTTTACTT TTAAGGCCAG CTTTCCAATA CAGCGATAAT ATTGCTAAAG AGTATGAAAA CAAATTCAAG AATCAAACCA CGCTTAAAGT TGAAGAGATC TTGCAAAATC AGGGCTATAA GGTTATTAAT GTGGATAGCA GCGATAAAGA CGATTTTTCT TTTGCGCAAA AAAAAGAAGG GTATTTGGCT

120

180

240

300

360

420

480

540

600

660

720

780

840

900

951

120

180

240

300

360

146

GTCGCTATGA ATGGCGAAAT TGTTTTACGC CCCGATCCTA AAAGGACCAT ACAGAAAAAA 420

TCAGAACCCG GGTTATTATT CTCCACTGGT TTGGATAAAA TGGAAAGGGT TTTAATCCCG 480

GCTGGGTTTG TCAAGGTTAC CATACTAGAG CCTATGAGTG GGGAATCTTT GGATTCTTTT 540

ACGATGGATT TGAGCGAGTT GGACATCCAA GAAAAATTCT TAAAAACCAC CCATTCAAGC 600

CATAGCGGAG GGTTAGTTAG CACTATGGTT AAGGGGACCC. ATAATTCTAA TGACGCAATT 660

AAGAGCGCTT TGAATAAGAT TTTTGCAAGT ATCATGCAAG AAATGGATAA GAAACTCACT 720

CAAAGGAATT TAGAATCTTA TCAAAAAGAC GCCAAGCiAAT TAAAAAACAA GAGAAACCGA 780

TAA 783 (2) INFORMATION ABOUT SEQ. No. 58:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 4149 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 SIGN: (A) NAME / KEY: different characters (B) PLACEMENT 1 ... 4149

(xi) SEQUENCE DESCRIPTION: SEQ. No. 58:

TTGAATTTTA ATAACCTTAC GGCTAATGGG GCGTTAAATT TTAATGGTTA TGCGCCCTCT 60 TTAACTAAGG CTTTAATGAA TGTCAGCGGG CAGTTTGTTT TAGGGAATAA TGGGGATATT 120 AATTTATCTG ACATCAATAT CTTTGACAAC ATCACAAAAT CTGTAACTTA CAACATCTTA 180 AACGCTCAAA AAGGGATTAC TGGCATTAGT GGGGCTAATG GCTATGAAAA AATCCTTTTT 240 TATGGCATGA AAATCCAAAA CGCTACCTAT AGCGATAATA ACAACATCCA AACTTGGTCG 300 TTTATAAACC CTCTCAATTC TTCTCAAATC ATTCAAGAGA GCATTAAAAA TGGGGATCTA 360 ACCATAGAAG TTTTAAATAA CCCTAACTCG GCTTCCAACA CTATTTTTAA TATCGCTCCT 420 GAGCTTTATA ATTACCAAGA TTCTAAGCAA AATCCTACCG GCTATAGCTA TGATTATAGC 480 GACAATCAAG CAGGCACTTA TTACTTGACA AGCAACATTA AAGGTCTTTT CACCCCTAAA 540 GGCTCTCÄAA CGCCTCAAAC CCCAGGCACT TATAGCCCAT TTAACCAGCC TTTGAATAGT 600 TTGAATATCT ACÄATAAGGG TTTTTCTAGC GAGAATTTAA AAACGCTTTT AGGGATCCTT 660 TCTCAAAATT CCGCCACCTT AAAAGAAATG ATTGAATCCA ACCAACTAGA CAATATCACT 720 AACATTAATG AAGTGTTGCA ACTCTTAGAT AAGATTAAAA TCACCCAAGC GCAAAAGCAA 780 GCGCTCCTAG AAACGATCAA CCATTTGACT GACAACATCA ATCAAACCTT TAATAACGGG 840 AATCTCGTTA TAGGCGCT AC CCAAGATAAT GTTACAAACT CTACTAGCTC TATATGGTTT 900 GGGGGCAATG GCTATAGCAG CCCTTGCGCG CTAGATAGCG CCACTTGTTC TTCTTTTAGA 960 AACACTTACT TGGGGCAATT ATTAGGCTCA ACTTCCCCTT ATTTAGGCTA CATTAACGCT 1020 GATTTTAAAG CTAAAAGCAT TTATATTACC GGGACAATTG GAAGTAGTAA CGCTTTTGAA 1080 AGCGGAGGGA GCGCGGATGT AACCTTTCAA AGCGCTAATA ACTTAGTGTT GAATAAAGCT 1140 AACATAGAAG CTCAAGCCAC AGACAATATC TTTAATCTTT TGGGTCAAGA AGGGATTGAT 1200 AAAATCTTTA ATCAGGGGAA TTTAGCGAAT GTTCTTAGTC AAATGGCTAT GGAAAAAATC 1260 AAGCAAGCCG GCGGTTTAGG GAACTTTATA GAAAACGCTC TAAGCCCTTT GAGTAAGGAA 1320 TTACCCGCTA GCTTGCAAGA TGAAACCTTA GGCCAACTTA TAGGTCAAAA TAACTTAGAT 1380 GATTTATTGA ATAATAGTGG AGTCATGAAT GAAATCCAAA ACATTATCAG TCAAAAACTA 1440 AGCATTTTTG GCAATTTTGT TACCCCATCC ATCATAGAAA ACTACCTTGC TAAGCAGTCT 1500 TTAAAAAGCA TGCTAGACGA TAAAGGGCTT TTGAATTTTA TCGGTGGGTA TATAGACGCT 1560 TCTGAATTAA GCTCTATTTT AGGCGTGATT TTAAAGGATA TTACTAACCC CCCTACAAGC 1620 CTGCAÄAAAG ACATTGGTGT GGTAGCGAAC GACTTGTTGA ACGAGTTTTT AGGACAAGAT 1680 GTTGTCAAAA AGCTAGAAAG TCAA GGCTTG GTGAGTAATA TCATCAATAA TGTTATTTCT 1740 CAAGGCGGGT TGAGCGGCGT TTATAATCAA GGTTTAGGGA GCGTGTTGCC GCCCTCTTTA 1800 CAAAACGCGC TCAAAGAAAA CGATTTAGGC ACTCTTTTAT CGCCTAGAGG CTTGCATGAT 1860 TTTTGGCAAA AAGGGTATTT TAACTTTTTA AGCAATGliCT ATGTTTTTGT CAATAACAGC 1920 TCTTTTAGTA ACGCTACTGG GGGTAGTTTG AATTTTGTCG CCAACAAGTC TATTATCTTT 1980 AATGGCGATA ATACGATTGA CTTTAGCAAG TATCAAGGCG CATTGATTTT TGCTTCTAAT 2040

147

GGTGTTTCTA

GGTTTGAATA

ACAACCAAAA

GTGCACGCTA

TCTCAAGTAA

CAAGCTAATA

ATTGATGGTA

AATGTCATGG

AGTCATGCTA

ATCCAATTCA

GCCATTTATT

AAGCTTTATG

ACCTATAACG

TCTCAAAATC

AATGATCCTA

GGCGTTCAAA

AATAAAATCT

TCCACAAAAG

AACCCTAATT

ATGAGTCGTT

CGCTTAGAAG

ATTTTAAAAT

GGGGCTAGTT

AGGTTTATTA

GCAAACATCA

ATCAAAAGAA

ATCAACTCCT

ACGACTGACG

TTTAAACCCC

ATGGATGATC

CTÄACGATCA

GTGATTGCGG

TTCATCGGTA

ATTATCACAG

GCTAGGTTTG

GCTTTTTAA

ATATCAATAT

ATGTGAGCGT

ACAGCTCTCC

ATAATTTCAC

CAAATAATAG

ATTTAACGAT

ATTTCACCTT

GGAATTTTAA

TTATCAATAC

ACGCTTCTTC

ACGGGTATAA

CGCTCATTGA

GGCAAGCCGT

AATACATTTA

TCAATAACCC

GCGTGGATAG

TTGAAACTAA

ATTTAACCAC

TTAAAAATGA

TAGCCAAGCT

CCCTTAAAAA

ACTCTCAAAG

TCATTAGTGG

AGGGCGTGAT

CTCAATCAGG

GCGAGCTAAC

ATGACCCCCT

CTAAAATCAA

AAGTAGGCTT

CTATTTACAA

ATTTTGCCCT

ATGTGGGCAG

ATAACACCCT

GCGGGGAGAT

GGCTTGATTA

CACCACCCTA

TCAAAAAGGA

TGCAAACTCT

TTTCTTAGGC

CGTTATAGGC

CACCAACGCT

AAACCAACAA

TAGCTATGGC

TCAAGGCACA

AAAAGAAGTG

CAACCAAATC

TATTAATGGC

GAGCGTTAAA

CACTTCCATT

ACAAGCCCCC

CATCGATCAA

AGGAAGCCCT

GATCGCTGGA

CGCCACTAAT

CTCTGACACT

CAAGCGATTC

GAATAGAGTT

AGGTACTGGA

TGTGGGAGGT

CTCTAGCAAT

CATGAGCTTG

ACTCTCAATC

TTATGGCTAT

AAGCTATTAT

CCAATTCAGA

AGAAAGTCGG

AGACTTATTC

AAGCTATAGA

AAGATTGTTC

TAAAGATATT

AACGCCACTA

GAAATTTGTA

AGCGTAACCC

ACAATCATCT

ACGCTCAATC

TTTAACAACG

GCGACTTTAA

GATTTGGTGT

GCGACGATCA

GGTACTTACA

ACAGGAGGCA

AAGCACATGG

GATGGCGGTT

CTTTATAATA

ACTTTAAAAC

GCTGGGGGAA

TTATTCGCTC

GATATTGCTA

ATTTTACAGA

TCAACTTTCG

GCTGATGCGA

AAAAATAATG

ACTTTATATG

TATGCCGCTT

GTCAATGTGG

AATGAGACTT

ATCAATCAGT

GATTTCATGT

TACATTGGTT

GCCAATGCTG

CATTATTTCA

ATTAATTCTA

GATGGTGGCA

AAAACCTTTT

AATATTACCG

ATGGCTTAAG

TCAATTTAGC

CCACTAATGA

CTAATGGGGC

TCAATGAAAA

CCTCTAACTC

GCACTAACGC

TTAACCTCAG

TGGCCAATAA

CGCTGATTGA

GTAGCCTGGA

TGATGACTGA

TAGTTGTAGG

AAGTGAAAAT

AATATATCGC

ATCAAGCGAT

CCTATTATCT

ACACTTTAGA

TCAACACCTA

CCCGTTCTGA

TCCCTAACGC

TGTGGGCGAC

GTATCAATGT

ATGGGTATAG

GCGTTTATAG

GGGGATACAA

CTTACAGATA

TTAAAGATAA

TGTCTGGTTT

ACCCTAATAA

ATAAAAACTC

TGGGGGATAA

GATACAACAC

ATGTGAATGC

GAAATATTGG

CCTTAATGCG

CAATTGCCCT

GTCTTTAAGC

TATTGATTTG

TGCGACCTTG

TACGGCTAAT

TAGTGGTTTG

TCATTCAGTT

TAACCCTTTG

TAGCGCTAAA

TAATTACCTT

CAACGGCTTA

CTTTAAGGAC

CGCTGTTTCT

TCAAATTCAG

TAATTGGCTC

AGAGAGCCAC

AGTCATCGCT

CACGCAGCAA

TTTCTTAGAA

TATGGATGTG

AGGAGTTGGA

AGGGTATGAT

CGGGTTCCAT

CCGAGCGTTT

TAAAACTTTC

CGACACTTGG

AAGCGTTATT

AAGGGGCATT

AAAATCCGTT

TTATTATTTT

AATGGTGCGT

TTTTGCTAGC

GGGCATAGGG

TATGCGCTAT

2100

2160

2220

2280

2340

2400

2460

2520

2580

2640

2700

2760

2820

2880

2940

3000

3060

3120

3180

3240

3300

3360

3420

3480

3540

3600

3660

3720

3780

3840

3900

3960

4020

4080

4140

4149 (2) INFORMATION ABOUT SEQ. No. 59:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 789 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 ... 789 (xi) SEQUENCE DESCRIPTION: SEQ. No. 59:

ATGAAAAAAA TTGGTTTGAG GAAGTGAGCG CTGAAGAGAT ATGAAAATCA ACCACACGAA GCAAGAGAGG ATTTAGAGGT TATTCTTTAG GGGGCGTGGC CTAGAAAATC AAAACGCTAG

CTTGTGTTTG GTTTTGAGTT TGCGGATATT TTCTACAAAC GGGGTTTTGC GCTAAAGGCG GCCACTACTC AATGAAAAAG GATGGACGAT AAAAGCAAGG TTGGACAATG GTGATGCTCA

TGGGTTTTTT AAAAGCCCAT TCAACGCCAA AGAGCCTAAA TGTTCCTCCC TAACCCGCAA AAATCCCTGC GTCTGTAAGG TTAGGGGAAT GGCGTTAAAA ATACAGAAAT CAATTTTGCC

120

180

240

300

360

148

AAAAACCCTG AAGAATTCGC CCAATTTTTT GAAATGAGAC TTCCTAAAAA TGGCAAGGTA 420 GATGAAGCAA GAATCAAAAA GCTTTACGAA GAAGTCCCCT CTTATAGGAA TTTTGCCGCC 480 TATATGAAAA CGATAGGGAT TAGCTCAAGC GTGGCTAATA CGCCTTATTA TAGCGTGCAT 540 GCGTTCAAGT TTAAAGATAA GAAAGAAAAA TTATTCÍCCTG CGAGGTGGAA ATTTGTGCCT 600 AAAGAGGGCG TTAAATACTT AAATCCTCAA GAATTAAAGC AAAAAGATTC AAATTATCTG 660 CTCTCTTCAT TCCAACAACA CCTTAAAAAT AAACCCATAG AATACCAAAT GTATTTGGTG 720 TTTGCGAATC AAAATGATGC CACCAACGAC ACGACCGCGC TTTGGAAAGG CAGCATAAGG 780 AATTATTAG 789 (2) INFORMATION ABOUT SEQ. ¢. 60:

{i, SEQUENCE CHARACTERISTICS:

(A) LENGTH: 741 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 ... 741

(xi, SEQUENCE DESCRIPTION: SEQ ID NO: 60:

ATGAAACAAT TTAAAAAGAA ACCAAAAAAG ATAAAACGAT CGCATCAAAA TCAAAAAACA 60 ATCTTAAAGC GTCCTTTATG GCTTATGCCT TTACTGATTG GCGGGTTTGC TAGTGGGGTG 120 TATGCGGATG GAACAGACAT TTTGGGGCTT AGTTGGGGGG AAAAAAGCCA AAAGGTATGC 180 GTGCATCGTC CATGGTATGC TATATGGAGT TGCGATAAAT GGGAGGAAAA AACACAACAA 240 TTTACAGGAA ACCAACTCAT CACAAAAACT TGGGCAGGGG GTAATGCGGC TAACTACTAC 300 CACTCTCAAA ACAACCAAGA CATCACAGCC ΑΑΤΤΤΑΑΛΛΑ ATGATAACGG CACTTATTTT 360 TTAAGCGGTC TGTATAACTA CACCGGAGGG GAATATAATG GGGGGAATTT AGACATTGAA 420 TTAGGCAGTA ACGCTACTTT TAATCTAGGT GCGAGTAGTG GGAATAGCTT CACTTCTTGG 480 TATCCTAATG GGCATACTGA TGTTACTTTT AGCGCTGGGA CTATCAATGT GAATAACAGC 540 GTAGAAGTGG GCAATCGTGT GGGATCGGGA GCTGGCACGC ACACCGGCAC AGCCACTTTA 600 AACTTGAACG CTAATAAGGT TACTATCAAT TCCAATATCA GCGCGTATAA AACTTCGCAA 660 GTGAATGTAG GCAATGCTAA CAGCGTTATT ACCATTAATT CGGTTTCTTT AAATGGGGAA TACTTGCAGT TCTTTAGCTA 720 G 741 (2) INFORMATION ON SEQ. No. 61:

(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) SIGN: (A, NAME / Key: different characters (B, PLACEMENT 1 ... 738

149 (xi) SEQUENCE DESCRIPTION: SEQ. No. 61:

ATGATAAAAA AGACCCTTGC ATCGGTTTTA TTAGGATTGA GTTTGATGAG TGTGTTAAAT 60 GCCAAAGAAT GCGTTTCGCC CATAACAAGA AGCGTTAAGT ATCATCAGCA AAGTGCTGAG 120 ATCAGAGCCT TGCAATTACA AAGTTACAAA ATGGCGAAAA TGGCGCTAGA CAATAACCTT 180 AAGCTCGTTA AAGACAAAAA GCCAGCCGTC ATCTTGGATT TAGATGAAAC CGTTTTGAAC 240 ACTTTTGATT ATGCGGGCTA TTTAGTCAAA AACTGCATTA AATACACCCC AGAAACTTGG 300 GATAAATTTG AAAAAGAAGG CTCTCTTACG CTCATTCCTG GAGCGCTAGA CTTTTTAGAA 360 TACGCTÄATT CTAAGGGCGT TAAGATTTTT TACATTTCTA ACCGCACCCA AAAAAATAAG 420 GCATTCACTT TAAAAACGCT CAAAAGCTTT AAGCTCCCCC AAGTGAGTGA AGAATCCGTT 480 TTGTTAAAGG AAAAAGGCAA GCCTAAAGCC GTTAGGCGGG AGTTAGTCGC TAAGGATTAT 540 GCGATTGTTT TACAAGTGGG CGACACTTTG CATGATTTTG ACGCCATTTT TGCTAAAGAC 600 GCTAAAAACA GCCAAGAACA ACAAGCCAAA GTCTTGCAAA ACGCTCAAAA AľTCGGCACA 660 GAATGGATCA TTTTACCCAA CTCTCTTTAT GGCACATGGG AAGATGGGCC TATAAAAGCA TGGCAAAATA AAAAATAA 720 738 (2) INFORMATION ON SEQ. No. 62:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 867 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 ... 867

(xi) SEQUENCE DESCRIPTION: SEQ. No. 62:

TTGTGGTGTT TAAAAACCCC TATCATAGGG CATGGCATGA AGAAAAAAGC AAAAGTCTTT 60 TGGTGTTGTT TTAAAATGAT TCGTTGGTTG TATTTGGCGG TCTTTTTTTT GTTGAGCGTA 120 TCAGACGCTA AAGAAATCGC TATGCAACGA TTTGACAAAC AAAACCATAA GATTTTTGAA 180 ATCCTTGCGG ATAAAGTGAG CGCCAAAGAC AATGTGATAA CCGCCTCAGG GAATGCGATC 240 CTATTGAATT ATGACGTGTA TATTCTAGCG GATAAGGTGC GTTATGACAC CAAGACTAAA 300 GAAGCGTTAT TAGAAGGCAA TATTAAGGTT TATAGGGGCG AGGGCTTGCT CGTTAAAACC 360 GATTATGTGA AATTGAGTTT GAACGAAAAA TATGAGATCA TTTTCCCCTT TTATGTCCAA 420 GACAGCGTGA GCGGGATTTG GGTGAGCGCG GATATTGCTA GCGGGAAGGA TCAAAAATAT 480 AAGATTAAAA ACATGAGCGC TTCAGGGTGC AGCATTGACA ACCCCATTTG GCATGTCAAT 540 GCGACTTCAG GCTCATTTAA CATGCAAAAA TCGCATTTGT CAATGTGGAA TCCTAAGATT 600 TATGTCGGCG ATATTCCTGT ATTGTATTTG CCCTATATTT TCATGTCCAC GAGCAATAAA 660 AGAACTACCG GGTTTTTATA CCCTGAGTTT GGCACTTCCA ACTTAGACGG CTTTATTTAT 720 TTGCAACCCT TTTATTTAGC CCCCAAAAAC TCATGGGATA TGACCTTTAC CCCACAAATC 780 CGTTACAAAA GGGGTTTTGG CTTGAATTTT GAAGCGCGCT ACATCAACTC TAAGACGCAG 840 GTTTTTATTC AATGCGCGCT ATTTTAG 867 (2) INFORMATION ABOUT SEQ. No. 63:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 387 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular (ii) MOLECULAR TYPE: DNA (genomic,

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

(A) ORGANISM: Helicobacter pylori (ix)

(A) NAME / KEY: various characters (B) LOCATION 1 ... 387 (xi) SEQUENCE DESCRIPTION: SEQ. No. 63:

TTGATGTTTA AAAAAATGTG TTTGAGCCTG CTAATGATAA GCGGTGTTTG TGTGGGGGCA 60 AAGGATTTGG ATTTCAAGCT GGATTATCGC GCGACTGGGG GGAAATTCAT AACCGGTGGT GATTAAAAAC 180 CTTATTGTCA ATAGGGGAAA TTCATGCGAA GCGACTAAAA AAGTAGAACC CAAATTTGGC 240 GATAAGTTTA AAAAAGAAAA ACTCTTTGAT CATGAATTAA AATACTCGCA ACAGATATTT 300 TACCGCCTGG ATTGCAAGCC TAACCAATTG TTAGAAGTTA AAATCATCAC GGACAAGGGC 360 GAATATTACC ATAAATTTTC CAAATAG 387 (2) INFORMATION ON SEQ. No. 64:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 510 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 ... 510 (xi) SEQUENCE DESCRIPTION: SEQ. No. 64:

ATGCAAGCGT TAAAATCATT GCTTGAAGTG ATTACAAAAC TCCAGAATCT AGGCGGCTAT 60 TTGATGCATA TAGCTATTTT CATCATTTTT ATTTGGATTG GAGGGCTTAA GTTTGTGCCT 120 TACGAAGCTG AAGGGATCGC CCCTTTTGTG GCCAACTCCC CTTTCTTTTC TTTCATGTAT 180 AAATTTGAAA AACCTGCATA CAAACAACAC AAAATGTCTG AATCCCAATC CATGCAAGAA 240 GAAATGCAAG ATAACCCTAA AATCGTTGAA AACAAAGAAT GGCATAAAGA AAACCGCACT 300 TATTTAGTGG CTGAAGGTTT AGGGATTACG ATCATGATCC TAGGCATTTT GGTGCTTTTG 360 GGGCTTTGGA TGCCTTTAAT GGGCGTAGTT GGGGGCTTGC TTGTCGCTGG AATGACGATC 420 ACCACCCTAT TCTTTTTTAT TCACAACGCC AGAAGTGTTT GTCAATCAGC ATTTCCCATG 480 GCTTTCTGGG GCTGGAAGGC TAGTGGTTAA 510 (2) INFORMATION ABOUT SEQ. No. 65:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 1464 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular (ii) MOLECULAR TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO

151

(iv) ANTI-SENSE: NO (Vi) ORIGINAL SOURCE: (A) ORGANISM: Helicobacter pylori (Ix) SIGN: (A) NAME / KEY: (B) LOCATION different characters 1 ... 1464 (Xi) SEQUENCE DESCRIPTION: SEQ. No. 65:

ATGATTGAAT

ATCGCTTTTA

GATAGCGCTG

CGCCGCCTTA

CAAATCAAAG

TTGAGGAATT

ATCAGAAAAA

ATCTTAAAAC

ATCCTTCAAA

CTATCGCTTT

GTTAAAATCT

TTTAAAAAGC

ACTGATTTGA

GAGGGGAAAT

CAAAAGGCGA

AACTACACCA

AAACTCACCG

ATCGTGGTGC

AGCGCTCTTA

AAAGAAAAGC

GGCACTATCA

CGCCAGGAAA

GAGCAAAATT

AATAACACTA

AAGATAGTCA

GGATGCAAAA

TTGCCGCCGG

CCAAAGTGGG

AAGACGCCTA

CCATGCATTT

TCGCTTTAGA

CGAACGTTTT

AAAGCCATTA

AAATCAGCGC

GGGCAAAATT

CTCTCAATGA

CCACAAGCTT

AAGAGTTGGA

TACAGGATTT

ATGAAAAAGC

CGCAAGATTT

CTCTCÄAGCC

AGCTTGTCTC

AAACCCGTCT

TTAAGGATTT

GTGAACTTAA

AAAAAGGGTT

TCAATCACCC

AAACGGATTT

AATACATTCA

TCATAGAAAG

AATGATAGGT

ACAGATTAAG

TGCTGAGTCT

AGAAAAAAGC

TTTAGGGCTT

TCAAAAAGAT

CCGCCCCAAG

TCTATTCCCC

GCAAGACAAA

AGAAGAGATG

TAAAACACGC

GGAATACTAC

TAAAAGCGTT

CTTAAGGAGC

TGAAAAAAAC

CCTTGAAGTC

TCAAATTAAA

GACTCAAGAA

TAAAGGGAAA

CCAAGAAGAG

TGTAACCATA

CTTTAGTGCA

TTTTGATAAA

ATAA

TATTTAGTGG

TGGGGGCAAT

ATTTCTCAAG

ATCCCTGATT

GCGCTAGATT

GGTGCTACCA

GGCGTTTTTG

CATTTTGAAG

AAAACCACCA

TTAGACATTC

AAAAAATATT

TCTTTATATT

CATAAAAACA

CAAGAGCAAG

TATATCGCTC

AACTCCCCCT

CTAAAACCAG

GACGAATTGC

ÄAAACCCTTA

AGCGTGGGTT

AGCGCGAAGT

GGTAATAAAG

GAAGAAAACC

GCGTTGATAG

TTACGATATG

ACAGCTTTTC

AAGAATTAGC

TTAAAGÄACT

CGCTCATCAA

AGCAAGAAGT

ATGAAGAATT

AAAGCGTTGA

CCCCTTTGGA

TTATCCTAAA

ATGAAAACCA

TTGACGCTAG

AGGTGTCTTA

TCAAGCATGA

TAAAAAAGGG

ATACTGCTGA

AGCCTTTTAA

AAAATTTTGA

TGGCGTTGCA

ATGTAAGCCC

TTATCAACAC

TGGTGCTTTA

AATACATGCA

AAGAATTGAA

GATAAGCACG

TTTAGATAGC

CCAAGAATAC

CACCGAAGAT

TCAAGCTTTA

GGCCAAAGAG

GTATAAAAAT

AAGGCTTTTA

GCAATCCAGT

TCCTAATGAT

TAGAAAGGAT

TTTAGAAAAA

TTTGGACAAA

TTTAAACATG

GAACGCACAA

AATCACGCAA

AGATGGTTTT

TGAAGCCAAA

AACTTTAGCT

TAATTTTGGA

CCTTTTTAAC

TCAAATCACA

GCGTTTAGTC

AAAACGCTAT

120

180

240

300

360

420

480

540

600

660

720

780

840

900

960

1020

1080

1140

1200

1260

1320

1380

1440

1464 (2) INFORMATION ABOUT SEQ. No. 66:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 429 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 ... 429 (xi) SEQUENCE DESCRIPTION: SEQ. No. 66:

ATGAAAACGA

TTTAACGCTC

ATGGCGCTAA

GAAACCCTAG

AAGTTTGACG

ATGTGGGGCA

ACTTTTATAA

CGCTTAACGC

ATAGCGTGGG

AGCAAAAAGT

ACATAAGTTT

TTCAAAATCT

AATTAAATTA

TGACCAAAAC

GCTTGTTTCT

GGCCATACTC

AGGGAGTTTC

TCTCATGAGC

CTATTTGCTT

ACGGATATAA

AGAGATCAGC

AATGACTATA

CAACCTAATG

CAAATGATGA

GGTGTCTTAT

AAGATATTAG

TAAAAATAGA

ATGATAAGAA

ATAATCTAGG

GCAATTACGG

CATTGGCATG

TCCTGAAGAT

GATCCCTAAA

TGTTAATATC

TATCAATGCG

TCCAAACAAT

120

180

240

300

360

152

TCTTTCATGT ATGGCTATGC GCCAACATAC TCAGATTCAT CGTTTTTACC ACCGATCTTA 420 GGGTATTAA 429 (2) SEQ ID NO. No. 67:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 627 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 pyluii SIGN: (A) NAME / KEY: different characters (B) PLACEMENT 1 ... 627

(xi) SEQUENCE DESCRIPTION: SEQ. No. 67:

TTGATCAACA ATAATAATAA CAATAAAAAA CTGAGACGCT TTTTTTTGAA AGTTCTCTTA 60 AGTCTCGTTG TTTTCAGTTC GTATGGGTCA GCAAATGACG ATAAAGAAGC CAAAAAAGAA 120 GCGCTAGAAA AAGAAAAAAA CACTCCCAAT GGGCTTGTTT ATACGAATTT AGATTTTGAT 180 AGTTTTAAAG CGACTATCAA AAATTTGAAA GACAAGAAAG TAACTTTCAA AGAAGTCAAT 240 CCCGATATTA TCAAAGATGA AGTTTTTGAC TTCGTGATTG TCAATAGAGT CCTTAAAAAA 300 ATAAAGGATT TGAAGCATTA CGATCCAGTT ATTGAAAAAA TCTTTGATGA AAAGGGTAAA 360 GAAATGGGAT TGAATGTAGA ATTACAGATC AATCCTGAAG TGAAAGACTT TTTTACTTTC 420 AAAAGCATCA GCACGACCAA CAAACAACGC TGCTTTCTAT CATTGCACGG AGAAACAAGA 480 GAAATTTTAT GCGATGATAA GCTATATAAT GTTTTATTGG CCGTATTCAA TTCTTATGAT 540 CCTAATGATC TTTTGAAACA ATT No. 68:

(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. No. 68:

ATGGCAGGCA CACAAGCTAT ATATGAATCA TCTTCTGCAG GATTCTTATC GCÄAGTCTCC 60 TCAATCATCT CAAGCACAAG TGGTGTCGCA GGGCCATTTG CAGGAATAGT AGCGGGCGCT 120 ATGACAGCAG CGATTATTCC TATTGTTGTG GGATTTACTA ATCCGCAAAT GACCGCTATC 180 ATGACCCAAT ACAATCAAAG CATCGCTGAA GCTGTAAGCG TGCCTATGAA AGCCGCTAAC 240 CAACAATACA ACCAATTGTA TCAAGGTTTT AACGATCAAA GCATGGCTGT GGGGAACAAT 300

153 atcttaaata tcagcaaatt AACAGGGGAA TTTAACGCGC AAGGCAACAC GCAAAGCGCG 360

CAAATTAGTG CTGTCAATAG TCAGATTGCA AGCATTTTAG CGAGTAACAC TACCCCTAAA 420

AATCCTAGCG CTATTGAAGC TTATGCGACG AATCAAATCG CTGTTCCTAG CGTGCCAACA 480

ACGGTTGAAA TGATGAGCGG TATATTAGGC AATATTACAA GCGCAGCACC AAAATACGCC 540

CTAGCTCTAC AAGAGCAACT GCGTTCTCAA GCAAGCAACA GCTCAATGAA TGATACAGCC 600

GATTCCCTTG ATAGCTGTAC CGCTTTAGGC GCACTTGTTG GCTCATCAAA AGTGTTTTTC 660

AGTTGCATGC AAATTTCTAT GACTCCTATG AGTGTTTCTA TGCCCACTGT TATGCCAAAT 720 ACCAGCGGTT GCCACTAA 738 (2) SEQ ID NO. No. 69:

(i, SEQUENCE CHARACTERISTICS:

(A) LENGTH: 1104 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 ... 1104 (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 69:

ATGATTAAAA GCGTAGAGAT TGAAAATTAC AAAAATTTTG AGCACCTTAA AATGGAAAAT 60 TTTAAACTCA TCAACTTTTT TACCGGTCAA AACGATGCGG GTAAAACCAA TCTTTTAGAA 120 GCTCTTTATA CCAACACAGG CCTTTGTGAT CCTACTGCCA ATCAAGTCAG TCTTCCTCCT 180 GAACATGCCG TGAATATTAG TGAATTCAGA AAAATCAAAC TCGATGCCGA CAACCTAAAA 240 ACCTTTTTTT ATCAAGGAAA CACCGCTAAT CCCATTAGTA TCCGCACTGA ATTTGAACAT 300 GCTACTATCC CTCTTACTAT CCAATACCCC ACACAAACCA GTTACAGCAA AGACATCAAT 360 TTGAATAGCG ATGATGCTCA TATGACAAAC CTTATAAACA CAACAATAAC GAAGCCACAG 420 CTCCAATTTT CCTACAATCC ATCCCTTTCC CCCATGACAA TGACTTATGA ATTTGAAAGG 480 CAAAACCTAG GTTTAATCCA TTCTAATTTA GATAAAATCG CTCAAACCTA TAAAGAAAAT 540 GCGATGTTTA TTCCTATAGA ATTATCTATT GTTAATTCTC TTAAAGCATT GGAAAATTTA 600 CAATTAGCAA GCÄAAGAAAA AGAATTGATT GAAATCCTAC AATGTTTCAA CCCTAATATT 660 TTAAATGCTA ATACAATAAG AAAGTCTGTC TATATCCAAA TCAAAGATGA AAACACACCG 720 CTAGAAGAAA GTCCCAÄAAG GCTTTTAAAT TTGTTTGGTT GGGGTTTTAT CAAATTCTTT 780 ATTATGGTGA GCATTCTTAT AGACAATCGT GTCAAGTATC TTTTTATTGA TGAAATAGAA 840 AGCGGTTTGC ACCATACA AA AATGCAAGAG TTTTTAAAAG CTCTGTTTAA GTTAGCTCAA 900 AAATTACAGA TTCAAATTTT TGCCACCACG CACAATAAGG AATTTTTATT AAACGCCATC 960 AACACGATAT CCGATAATGA AACGGGAGTT TTTAAAGACA TAGCCTTGTT TGAGCTTGAA 1020 AAAGAAAGCG CTTCTGGCTT TATCAGACAC AGCTATTCTA TGCTAGAAAA AGCGCTTTAT 1080 AGGGGTATGG AGGTTAGAGG Ctga 1104 (2) INFORMATION ON SEQ. No. 70:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 1230 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

154

(vi) ORIGINAL SOURCE: Helicobacter pylori (A) ORGANISM: (Ix, SIGN: (A) NAME / KEY: (B) LOCATION different characters 1 .. .1230 (Xi) SEQUENCE DESCRIPTION: SEQ. No ..- 70:

ATGTCCTTGA TTAGAGTGAA TGGGGAAGCT TTTAAACTCT CTTTGGAAAG TTTAGAAGAA GATCCTTTTG AAACTAAAGA AACGCTAGAA ACGCTAGAAA CGCTTATCAA ACAAACGAGC GTTGTTTTAT TGGCCGCTGG GGAGTCTAAG CGTTTTTCTC GTGCGATTAA AAAGCAGTGG CTACGCTCTC ACCACACCCC CTTATGGCTC AGCGTGTATG AAAGCTTTAA AGAAGCCCTA GACTTTAAGG AAGTCATTCT AGTTGTAAGC GAATTGGATT ATGTTTATAT CCAACGCCAT TACCCCAAAA TCAAGCTTGT AAAAGGCGGG GCATCAAGGC AAGAATCCGT GCGTAACGCT TTGAAAGTAA TTGATAGCAC TTACACGATC ACCAGCGATG TGGCTAGGGG TTTAGCGAAT ATGGAAGCGC TTAAAAGCTT GTTTTTAACC CTCCAACAAA CGAGCCATTA TTGCATCGCC CCTTACTTGC CTTGCTATGA CACAGCGATC TATTATAACG AGGCTTTAGA TAGAGAAGCG ATCAAACTCA TTCAAACCCC GCAATTAAGC CACACCAAAA CGCTCCAATC AGCCCTAAAC CAAGGGGGTT TTAAAGATGA AAGCAGCGCG ATTTTACAAG CTTTCCCTAA CTCTGTGAGC TATATTGAAG GCAGTAAGGA TTTGCACAAA CTCACCACAA GCGGCGATTT AAAGTTTTTT ACGCCTTTTT TTAACCCAGC AAAGGACACT TTTATAGGCA TGGGTTTTGA TACGCATGCG TTCATTAAAG ATAAGCCTAT GGTTTTAGGG GGGGTTGTTT TGGATTGCGA GTTTGGGTTA AAGGCTCATA GCGATGGCGA TGCTTTATTG CATGCGGTTA TTGATGCGAT TTTAGGAGCG ATTAAAGGGG GGGATATTGG CGAATGGTTC CCTGATAATG ACCCCAAATA CAAAAACGCC TCTTCTAAAG AGCTTTTAAA AATCGTGTTG GATTTTTCTC AAAGCATTGG GTTTGAATTG CTTGAAATGG GAGCGACCAT CTTTAGCGAA ATCCCTAAAA TCACTCCTTA CAAACCGGCG ATTTTAGAGA ATTTGAGCCA ACTTTTGGGT TTAGAAAAAT CTCAAATCAG CTTGAAAGCC ACTACAATGG AAAAAATGGG GTTCATTGGC AAACAAGAAG GGCTGTTAGT CCAAGCGCAT GTGAGCATGC GTTATAAACA AAAACTTTAA (2) INFORMATION ON SEQ. No. 71:

(i, SEQUENCE CHARACTERISTICS:

(A) LENGTH: 813 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 ... 813 (xi, SEQUENCE DESCRIPTION: SEQ ID NO: 71:

ATGAAAAAGT TTGTAGCTTT AGGGCTTCTA TCCGCGGTTT TAAGCTCTTC GTTGTTAGCC GAAGGTGATG GTGTTTATAT AGGGACTAAT TATCAGCTTG GACAAGCCCG TTTGAATAGC AATATTTATA ATACAGGGGA TTGCACAGGG AGTGTTGTAG GTTGCCCCCC AGGTCTTACC GCTAATAAGC ATAATCCAGG AGGCACCAAT ATCAATTGGC ACTCCAAATA CGCTAATGGG GCTTTGAATG GTTTTGGGTT GAATGTGGGT TATAAGAAAT TCTTCCAATT CAAGTCGCTA GATATGACAA GCAAGTGGTT TGGTTTTAGA GTGTATGGGC TTTTTGATTA CGGGCATGCC GATTTAGGTA AACAAGTTTA TGCACCTAAT AAAATCCAGT TGGATATGGT CTCTTGGGGT GTGGGGAGCG ATTTGTTAGC TGATATTATT GATAÄAGACA ACGCTTCTTT TGGTATTTTT GGTGGGGTCG CTATCGGCGG TAACACTTGG AAAAGCTCTG CAGCAAACTA TTGGAAAGAG CAAATCATTG AAGCCAAAGG TCCTGATGTT TGTACCCCTA CTTATTGTAA CCCTAATGCC CCTTATAGCA CCAACACTTC AACCGTCGCT TTGTGTGT

120

180

240

300

360

420

480

540

600

660

720

780

840

900

960

1020

1080

1140

1200

1230

120

180

240

300

360

420

480

540

600

660

720

155

AAATTTTTGA GCGCGGGTCC TAACGCTACT AACCTTTATT ACCATTTGAA ACGGGATTAT 780 TCGCTTTATT TGGGGTATAA CTACACTTTT TAA 813 (2) SEQ ID NO. No. 72:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 1317 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 ... 1317 (xi) SEQUENCE DESCRIPTION: SEQ. No. 72:

ATGGCTTACA AACCTAACAA AAAGAAGTTA AAAGAATTAA GAGAGCAACC GAATTTATTT 60

AGCATCTTAG ATAAGGGCGA TGTTGCAACA AACAATCCTG TTGAAGAGTC AGACAAGGCC 120

AATAAAATAC AAGAGCCACT CCCTTATGTC GTGAAAACGC AAATCAATAA AGCAAGCATG 180

ATTTCTAGAG ATCCTATTGA ATGGGCAAAG TATTTAAGCT TTGAAAAACG AGTCTATAAG 240

GATAATAGTA AÄGAAGATGT CAATTTCTTT GCCAATGGTG AGATAAAAGA AAGTTCTCGT 300

GTTTATGAAG CGAATAAAGA AGGGTTTGAA AGGCGCATCA CTAAAAGATA CGATCTGATT 360

GATAGAAATA TTGATAGAAA TAGAGAATTT TTTATAAAAG AAATTGAAAT TCTAACCCAC 420

ACAAACAGCT TAAAAGAATT · GAAAGAGCAA GGGTTAGAAA TCCAATTGAC CCACCATAAT 4 80

GAAACGCATA AGAAAGCCTT AGAAAATGGC AATGAAATCG TTAAAGAATA CGACCATCTT 540

AAAGATATTT ACCAAGAAGT AGAAAGAACA AAAGATGGTG GATTGGTAAG AGAAATAATC 600

CCCAGTATTT CTAGCGCTGA GTATTTCAAG CTTTACAACA AACTGCCTTT TGAATCAATA 660

AACAATGAAA ATACCAAACT GAATACTAAC GACAATGAAG AAGTTAAAAA ACTAGAATTT 720

GAATTAGCTA AAGAAGTGCA TATTTTAATC CTAGAGCAAC AATTGCTTTC AGCAACAAAT 780

TATTATTCTT GGATAGATAA AGATGATAAT GCGAATTTTG CTTGGAAAAT GCATAGGCTT 840

ATCAATGAAA ATAAACTCAA AGAAAACCAT CTCAGCGCCA ATAACGCTAA TAAGATTAAG 900

CAATTTTTCT TTAATAATGG TTCTATTTTA GGCTGGACTA AAGAAGAACA AAGCGCTATA 960

CAAGAAAACA GAGATTATTC TTTAAGAAGC GCTCTTTTAA GTTTAGAAGA AATCGCTCAA 1020

GCAAAAATTG AATTGCAAAA ATACTATGAA AGCGTTTATG TTAATGGTGA TGGGAATAAA 1080

AGAGAAATCA AGCCTTTTAA AGAAATTTTA AGAGACACCA ACAATTTTGA AAAAGCTTAT 1140

AAGGAGCGTT ATGACAAATT GGTAAGCTTG AGTGCAGCAA TCATTCAAGC TAAAGAGGGT 1200

GGTAATGAGC GACCAAATTC TAGTGCAAAT AACAATAACC CTATTAAAAA TACAATAGAG 1260

ACTAATACTT CTAACAATAT TATTCAAAAT AATGATAATA TAATCATCCA AATTTAA 1317 (2) INFORMATION ABOUT SEQ. No. 73:

(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

156 (ix) SIGN:

(A) NAME / KEY: various characters (B) LOCATION 1 ... 648 (xi) SEQUENCE DESCRIPTION: SEQ. No. 73:

ATGCAAGCGT TAAAATCATT GCTTGAAGTG ATTACAAAAC TCCAGAATCT AGGCGGCTAT TTGATGCATA TAGCTATTTT CATCATTTTT ATTTGGATTG GAGGGCTTAA GTTTGTGCCT TACGAAGCTG AAGGGATCGC CCCTTTTGTG GCCAACTCCC CTTTCTTTTC TTTCATGTAT AAATTTGAAA AACCTGCATA CAAACAACAC AAAATGTCTG AATCCCAATC CATGCAAGAA GAAATGCAAG ATAACCCTAA AATCGTTGAA AACAAAGAAT GGCATAAAGA AAACCGCACT TATTTAGTGG CTGAAGGTTT AGGGATTACG ATCÄTGATC'C TAGGCATTTT GGTGCTTTTG GGGCTTTGGA TGCCTTTAAT GGGCGTAGTT GGGGGCTTCC TTGTCGCTGG AATGACGATC ACCACCCTAT CTTTTTTATT CACAACGCCA GAAGTGTTTG TCAATCAGCA TTTCCCATGG CTTTCTGGGG CTGGAAGGCT AGTGGTTAAA GACTTGCCGT TATTTGCTGG AGGCTTGTTT GTGGCCGGAT TTGATGCGAA ACGCTATTTG GAGGGTAAAG GGTTTTGCTT GATGGACCGAC TCATCGGTTCT No. 74:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 186 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 ... 186 (xi) SEQUENCE DESCRIPTION: SEQ. No. 74:

120

180

240

300

360

420

480

540

600

648

Met Ile Lys Arg Ile Ala Cys Ile Leu Ser Leu Ser Ala Ser Leu Ala 1 5 10 15 Leu Ala Gly Glu wall same time Gly Phe Phe Met Gly Ala Gly Tyr gin gin 20 25 30 Gly Arg Tyr Gly for Tyr same time Ser same time Tyr Ser Asp Trp Arg His Gly 35 40 45 same time Asp Leu Tyr Gly Leu same time Phe Lys Leu Gly Phe wall Gly Phe Ala 50 55 60 same time Lys Trp Phe Gly Ala Arg wall Tyr Gly Phe Leu Asp Trp Phe same time 65 70 75 80 Thr Ser Gly Thr Glu His Thr Lys Thr same time Leu Leu Thr Tyr Gly Gly 85 90 95 Gly Gly Asp Leu Ile wall same time Leu Ile for Leu Asp Lys Phe Ala Leu 100 105 110 Gly Leu Ile Gly Gly wall gin Leu Ala Gly same time Thr Trp Met Phe for 115 120 125 Tyr Asp wall same time gin Thr Arg Phe gin Phe Leu Trp same time Leu Gly Gly 130 135 140 Arg Met Arg wall Gly Asp Arg Ser Ala Phe Glu Ala Gly wall Lys Phe 145 150 155 160 for Met wall same time gin Gly Ser Lys Asp wall Gly Leu Ile Arg Tyr Tyr 165 170 175 Ser Trp Tyr wall Asp Tyr wall Phe Thr Phe 180 185

(2, SEQ ID NO: 75:

(i) SEQUENCE CHARACTERISTICS:

157 (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)

(A) NAME / KEY: various characters (B) LOCATION 1 ... 116 (xi, SEQUENCE DESCRIPTION: SEQ ID NO: 75:

Leu Met Arg Ile Ile Ile Arg Leu Leu Ser Phe Lys Met same time Ala Phe 1 5 10 15 Leu Lys Leu Ala Leu Ala Ser Leu Met Gly Gly Leu Trp Tyr Ala Phe 20 25 30 same time Gly Glu Gly Ser Glu Ile wall Ala Ile Gly Ile Phe wall Leu Ile 35 40 45 Leu Phe wall Phe Phe Ile Arg for wall Ser Phe gin Asp for Glu Lys 50 55 60 Arg Glu Glu Tyr Ile Glu Arg Leu Lys Lys same time His Glu Arg Lys Met 65 70 75 80 Ile Leu gin Asp Lys gin Lys Glu Glu gin Met Arg Leu Tyr gin Ala 85 90 95 Lys Lys Glu Arg Glu Ser Arg gin Lys gin Asp Leu Lys Glu gin Met 100 105 110 Lys Lys Tyr Ser 115

(2) INFORMATION ABOUT SEQ. No. 76:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 345 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 ... 345

(xi, SEQUENCE DESCRIPTION: SEQ ID NO: 76:

Met wall Lys His Tyr Leu Phe Met Ala wall Ser gin wall Phe Phe Ser 1 5 10 15 Phe Phe Leu wall Leu Phe Phe Ile Ser Ser Ile wall Leu Leu Ile Ser 20 25 30 Ile Ala Ser wall Thr Leu wall Ile Lys wall Ser Phe Leu Asp Leu wall 35 40 45 gin Leu Phe Leu Tyr Ser Leu for Gly Thr Ile Phe Phe Ile Leu for 50 55 60 Ile Thr Phe Phe Ala Ala Cys Ala Leu Gly Leu Ser Arg Leu Ser Tyr 65 70 75 80 Asp His Glu Leu Leu wall Phe Phe Ser Leu Gly wall Ser for Lys Lys 85 90 95

158

Met Thr Lys Ala 100 Phe Val Pro Leu Ser Leu I.nu Val Ser Ala Leu 105 110 Leu Ala Phe Ser Leu Ile Leu Ile for Thr :; '- r Lys Ser Ala Tyr Tyr 115 120 125 Gly Phe Leu Arg gin Lys Lys Asp Lys Ile :: Λ ρ Ile same time Ile Arg Ala 130 135 140 Gly Glu Phe Gly gin Lys Leu Gly Asp Trp Iil'U wall Tyr wall Asp Lys 145 150 1! »5 160 Thr Glu same time same time Ser Tyr Asp same time Leu wall I.cu Phe Ser same time Lys Ser 165 170 175 Leu Ser gin Glu Ser Phe Ile Leu Ala gin I.ys Gly same time Ile same time same time 180 185 190 gin same time Gly wall Phe Glu Leu same time Leu Tyr A: ·, n Gly His Ala Tyr Phe 195 200 205 Thr gin Gly Asp Lys Met Arg Lys wall Asp LLI '; Glu Glu Leu His Leu 210 215 220 Arg same time Lys Leu Lys Ser Phe same time Ser same time A :: p Ala Ala Tyr Leu gin 225 230 ? < ^r , 240 Gly Thr Asp Tyr Leu Gly Tyr Trp Lys Lys A l.i Phe Gly Lys same time Ala 245 250 255 same time Lys same time gin Lys Arg Arg Phe Ser gin Al.i Ile Leu wall Ser Leu 260 265 270 Phe for Leu Ala Ser wall Phe Leu Ile for Leu Phe Gly Ile Ala same time 275 280 285 for Arg Phe Lys Thr same time Trp Ser Tyr Phe Tyr wall Leu Gly Ala wall 290 295 300 Gly wall Tyr Phe Leu Met wall His wall Ile Ser Thr Asp Leu Phe Leu 305 310 315 320 Met Thr Phe Phe Phe for Phe Ile Trp Ala Pho Ile Ser Tyr Leu Leu 325 330 335 Phe Arg Lys Phe Ile Leu Lys Arg Tyr

340 345 (2, SEQ ID NO: 77:

(i, SEQUENCE CHARACTERISTICS:

(A) LENGTH: 276 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: miscellaneous: letters (B) LOCATION ... 276 (Xi. SEQUENCE DESCRIPTION: SEQ. No. 77: Met Lys Lys Lys Ala Lys Val Phe Trp Cys Cys Phe Lys Met Ile Arg 1 5 10 15 Trp Leu Leu Ala Val Phe Phe Leu Leu Ser wall Ser Asp Ala Lys 20 25 30 Glu Ile Ala Gin Arg Phe Asp Lys gin same time His Lys Ile Phe Glu 35 40 45 Ile Leu Ala Asp Lys Val Ser Ala Lys Asp same time wall Ile Thr Ala Ser 50 55 60 Gly same time Ala ile Leu Leu Asn Tyr Asp wall Tyr Ile Leu Ala Asp Lys 65 70 75 80 wall Arg Lys Thr Lys Glu Ala Leu Leu Glu Gly same time Ile 85 90 95 Lys wall Tyr Arg Gly Glu Gly Leu Leu wall I.ys Thr Asp Tyr wall Lys

159

100 105 110 Leu Ser Leu same time Glu Lys Tyr Glu Ile Ile Phe for Phe Tyr wall gin 115 120 125 Asp Ser wall Ser Gly Ile Trp wall Ser Ala Asp Ile Ala Ser Gly Lys 130 135 140 Asp gin Lys Tyr Lys Ile Lys same time Met Ser Ala Ser Gly Cys Ser Ile 145 150 155 160 Asp same time for Ile Trp His wall same time Ala Thr Ser Gly Ser Phe same time Met 165 170 175 gin Lys Ser His Leu Ser Met Trp same time for Lys Ile Tyr wall Gly Asp 180 185 190 Ile for wall Leu Tyr Leu for Tyr Ile Phe Met Ser Thr Ser same time Lys 195 200 205 Arg Thr Thr Gly Phe Leu Tyr for Glu Phe Gly Thr Ser same time Leu Asp 210 215 220 Gly Phe Ile Tyr Leu gin for Phe Tyr Leu Ala for Lys same time Ser Trp 225 230 235 240 Asp Met Thr Phe Thr for gin Ile Arg Tyr Lys Arg Gly Phe Gly Leu 245 250 255 same time Phe Glu Ala Arg Tyr Ile same time Ser Lys Thr gin wall Phe Ile gin 260 265 270 Cys Ala Leu Phe 275 (2) INFORMATION 0 SEQ. No. 78:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 224 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 ... 224

(xi) SEQUENCE DESCRIPTION: SEQ. No. 78:

Met Ile Arg Leu Lys Gly Leu same time Lys Thr Leu Lys Thr Ser Leu Leu 1 5 10 15 Ala Gly wall Leu Leu Gly Ala Thr Ala for Leu Met Ala Lys for Leu 20 25 30 Leu Ser Asp Glu Asp Leu Leu Lys Arg wall Lys Leu His same time Ile Lys 35 40 45 Glu Asp Thr Leu Thr Ser Cys same time Ala Lys wall Asp Gly Ser gin Tyr 50 55 60 Leu same time Ser Gly Trp same time Leu Ser Lys Glu Phe for gin Glu Tyr Arg 65 70 75 80 Glu Lys Ile Phe Glu Cys wall Glu Glu Glu Lys His Lys gin Ala Leu 85 90 95 same time Leu Ile same time Lys Glu Asp Thr Lys Asp Lys Glu Glu Leu Ala Lys 100 105 110 Lys Ile Lys Glu Ile Lys Glu Lys Ala Lys wall Leu Arg gin Lys Phe 115 120 125 Met Ala Phe Glu Met Lys Glu His Ser Lys Glu Phe for same time Lys Lys 130 135 140 gin Leu gin Thr Met Leu Glu same time Ala Phe Asp same time Gly Ala Glu Ser 145 150 155 160 Phe Ile Asp Asp Trp His Glu Arg Phe Gly Gly Ile Ser Arg Glu same time 165 170 175

160

Thr Tyr Lys Ala Leu Gly White Lys Glu Tyr Ser Asp Glu Gly Lys Ile 180 185 190 Leu For Leu Ala Lys Glu Val ile Leu Asp Ys:; η lys Lys lys Leu 195 200 205 Lys Lys Ala Leu Met Leu Asp Asn Pro Tyr Leu Leu Trp Leu wall 210 215 220

(2) INFORMATION ABOUT SEQ. No. 79:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 429 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) LOCATION 1 ... 429

(xi) SEQUENCE DESCRIPTION: SEQ. No. 79:

Met for Tyr Ala Leu Arg Lys Arg Phe Phe Lys Arg Leu Leu Leu Phe 1 5 10 15 Phe Leu Ile wall Cys Met Ile same time Leu His Ala Lys Ser Tyr Leu Phe 20 25 30 Ser for Leu for for Ala His gin gin Ile Ile Lys Thr Glu for Cys 35 40 45 Ser Leu Glu Cys Leu Lys Asp Leu Met Leu gin same time gin Ile Phe Ser 50 55 60 Phe wall Ser gin Tyr Asp Asp same time same time gin Asp Glu Ser Leu Lys Thr 65 70 75 80 Tyr Tyr Lys Asp Ile Leu same time Lys Leu same time for wall Phe Ile Ala Ser 85 90 95 gin Thr for Ala Lys Glu Ser Tyr Glu for Lys Ile Glu Leu Ala Ile 100 105 110 Leu Leu for Lys Lys wall wall Gly Arg Tyr Ala Ile Leu wall Met same time 115 120 125 Thr Leu Leu Ala Tyr Leu same time Thr Arg same time same time Asp Phe same time Ile gin 130 135 140 wall Phe Asp Ser Asp Glu Glu Ser for Glu Lys Leu Glu Glu Thr Tyr 145 150 155 160 Lys Glu Ile Glu Lys Glu Lys Phe for Phe Ile Ile Ala Leu Leu Thr 165 170 175 Lys Glu Gly wall Glu same time Leu Leu gin same time Thr Thr Ile same time Thr for 180 185 190 Thr Tyr wall for Thr wall same time Lys Thr gin Leu Glu same time His Thr Glu 195 200 205 Leu Ser Leu Ser Glu Arg Leu Tyr Phe Gly Gly Ile Asp Tyr Lys Glu 210 215 220 gin Leu Gly Met Leu Ala Thr Phe Ile Ser for same time Ser for wall Ile 225 230 235 240 Glu Tyr Asp Asp Asp Gly Leu Ile Gly Glu Arg Leu Arg gin Ile Thr 245 250 255 Glu Ser Leu same time wall Glu wall Lys His gin Glu same time Ile Ser Tyr Lys 260 265 270 gin Ala Thr Ser Phe Ser Lys same time Phe Arg Lys His Asp Ala Phe Phe 275 280 285 Lys same time Ser Thr Leu Ile Leu same time Thr for Thr Thr Lys Ser Gly Leu 290 295 300 Ile Leu Ser gin Ile Gly Leu Leu Glu Tyr Lys for Leu Lys Ile Leu

161

305 310 315 320 Ser Thr gin Ile same time Phe same time for Ser Leu Leu Leu Leu Thr gin for 325 330 335 Lys Asp Arg Lys same time Leu Phe Ile wall same time Ala Leu gin same time Ser Asp 340 345 350 Glu Thr Leu Ile Glu Tyr Ala Ser Leu Leu Glu Ser Asp Leu Arg His 355 360 365 Asp Trp wall same time Tyr Ser Ser Ala Ile Gly Leu Glu Met Phe Leu same time 370 375 380 Thr Leu Asp for His Phe Lys Lys Ser Phe gin Glu Ser Leu Glu Asp 385 390 395 400 same time gin wall Arg Tyr His same time gin Ile Tyr gin Ala Leu Gly Tyr Ser 405 410 415 Phe Glu for Ile Lys same time Glu Ser Glu Thr Lys Lys Glu 420 425

(2) INFORMATION ABOUT SEQ. No. 80:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 455 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 ... 455 (xi) SEQUENCE DESCRIPTION: SEQ. No. 80:

wall Leu Lys Phe gin Lys Leu for Leu Leu Phe wall Ser Ile Leu Tyr 1 5 10 15 same time gin Ser for Leu Leu Ala Phe Asp Tyr Lys Phe Ser Gly wall Ala 20 25 30 Glu Ser wall Ser Lys wall Gly Phe same time His Ser Lys Leu same time Ser Lys 35 40 45 Glu Gly Ile Phe for Thr Ala Thr Phe wall Thr Ala Thr Ile Lys Leu 50 55 60 gin wall Asp Ser same time Leu Leu for Lys same time Ile Glu Lys His Ser Leu 65 70 75 80 Lys Ile Gly wall Gly Gly Ile Leu Gly Ala Leu Ala Tyr Asp Ser Thr 85 90 95 Lys Thr Leu Ile Asp gin Ala Thr His gin Ile Tyr Gly Ser Glu Leu 100 105 110 Phe Tyr Leu Ile Gly Arg Trp Trp Gly Phe Leu Gly same time Ala for Trp 115 120 125 Lys Asp Ser Leu Ile Glu Ser Asp Ala His Thr Arg same time Tyr wall Leu 130 135 140 Tyr same time Ser Tyr Leu Phe Tyr Ser Tyr Gly Asp Lys Phe His Leu Lys 145 150 155 160 Leu Gly Arg Tyr Leu Ser same time Met Asp Phe Met Ser Ser Tyr Thr gin 165 170 175 Gly Phe Glu Leu Asp Tyr Lys Ile same time Ser Lys Ile Ala Leu Lys Trp 180 185 190 Phe Ser Ser Phe Gly Arg Ala Leu Ala Phe Gly gin Trp Ile Arg Asp 195 200 205 Trp Tyr Ala for Ile wall Thr Glu Asp Gly Arg Lys Glu wall Tyr Asp 210 215 220 Gly Ile His Ala Ala gin Leu Tyr Phe Ser Ser Lys His wall gin wall 225 230 235 240

162

Met For Phe Ala Tyr Phe Ser Pro Lys White Tyr Gly Ala Pro Gly Val 245 250 255 Lys Ile His Ile Asp Ser same time for Lys Phe would. ·? Gly Leu Gly Leu Arg 260 265 270 Ala gin Thr Thr Ile same time wall Ile Phe for V.il Tyr Ala Lys Asp Leu 275 280 285 Tyr Asp wall Tyr Trp Arg same time Ser Lys Ile C.ly Glu Trp Gly Ala Ser 290 295 300 Leu Leu Ile His gin Arg Phe Asp Tyr same time Glu Phe same time Phe Gly Phe 305 310 315 320 Gly Tyr Tyr gin same time Phe Gly same time Ala same time ΛΙ.ι Arg Ile Gly Trp Tyr 325 330 335 Gly same time for Ile for Phe same time Tyr Arg same time Λ;: η Ser wall Tyr Gly Gly 340 345 350 wall Phe Ser same time Ala Ile Thr Ala Asp Ala V.l i Ser Gly Tyr wall Phe 355 360 365 Gly Gly Gly wall Tyr Arg Gly Phe Leu Trp Gly Ile Leu Gly Arg Tyr 370 375 380 Thr Tyr Ala Thr Arg Ala Ser Glu Arg Ser 1 li < same time Leu same time Leu Gly 385 390 3'b ') 400 Tyr Lys Trp Gly Ser Phe Ala Arg wall Asp V.il same time Leu Glu Tyr Tyr 405 410 415 wall wall Ser Met His same time Gly Tyr Arg Leu Asp Tyr Leu Thr Gly for 420 425 430 Phe same time Lys Ala Phe Lys Ala Asp Ala gin Asp Arg Ser same time Leu Met 435 440 445 wall Ser Met Lys Phe Phe Phe

450 455 (2) INFORMATION ABOUT SEQ. No. 81:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 282 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) LOCATION ... 282 (Xi) SEQUENCE DESCRIPTION: SEQ. NO.: L 31: Met Gly Cys Ser Phe White Phe Lys Lys wall Arg wall Tyr Ser Lys Met 1 5 10 15 Leu wall Gly Leu Ser Ser wall Leu Ile Gly Cys Ala Met same time 20 25 30 for Ser Ala Glu Thr Lys Lys for same time Asp Ala Lys same time gin gin for 35 40 45 wall gin Thr His Glu Arg Met Thr Thr Ser Ser Glu His wall Thr for 50 55 60 Leu Asp Phe Asn Tyr Pro wall His Ile wall gin Ala for gin same time His 65 70 75 80 His wall Val Gly White Leu Met for Arg Ile gin wall Ser Asp same time Leu 85 90 95 Lys for Tyr ile Asp Lys Phe gin Asp Ala Leu Ile same time gin Ile gin 100 105 110 Thr Ile Phe Glu Lys Arg Gly Tyr gin wall Leu Arg Phe gin Asp Glu 115 120 125 Lys Ala Asu Val Gin Asp Lys Lys Lys Ile Phe Ser wall Leu Asp

163

130 135 140 Leu Lys Gly Trp wall Gly Ile Leu Glu Asp Leu Lys Met same time Leu Lys 145 150 155 160 Asp for same time Ser for same time Leu Asp Thr Leu wall Asp gin Ser Ser Gly 165 170 175 Ser wall Trp Phe same time Phe Tyr Glu for Glu Ser same time Arg wall wall His 180 185 190 Asp Phe Ala wall Glu wall Gly Thr Phe gin Ala Ile Thr Tyr Thr Tyr 195 200 205 Thr Ser Thr same time same time Ala Ser Gly Gly Phe same time Ser Ser Lys Ser wall 210 215 220 Ile His Glu same time Leu Asp Lys same time Arg Glu Asp Ala Ile His Lys Ile 225 230 235 240 Leu same time Arg Met Tyr Ala wall wall Met Lys Lys Ala wall Thr Glu Leu 245 250 255 Thr Lys Glu same time Ile Ala Lys Tyr Arg Asp Ala Ile Asp Arg Met Lys 260 265 270 Gly Phe Lys Ser Ser Met for gin Lys Lys 275 280

(2, SEQ ID NO: 82:

(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: 82:

Met Lys Leu Arg Ala Ser wall Leu Ile Gly wall Ala Ile Leu Cys Leu 1 5 10 15 Ile Leu Ser Ala Cys Ser same time Tyr Ala Lys Lys wall wall Lys gin Lys 20 25 30 same time His wall Tyr Thr for wall Tyr same time Glu Leu Ile Glu Lys Tyr Ser 35 40 45 Glu Ile for Leu same time Asp Lys Leu Lys Asp Thr for Phe Met wall gin 50 55 60 wall Lys Leu for same time Tyr Lys Asp Tyr Leu Leu Asp same time Lys gin wall 65 70 75 80 wall Leu Thr Phe Lys Leu wall His His Ser Lys Lys Ile Thr Leu Ile 85 90 95 Gly Asp Ala same time Lys Ile Leu gin Tyr Lys same time Tyr Phe gin Ala same time 100 105 110 Gly Ala Arg Ser Asp Ile Asp Phe Tyr Leu gin for Thr Leu same time gin 115 120 125 Lys Gly wall wall Met Ile Ala Ser same time Tyr same time Asp same time for same time same time 130 135 140 Lys Glu Lys for gin Thr Phe Asp wall Leu gin Gly Ser gin for Met 145 150 155 160 Leu Gly Ala same time Thr Lys same time Leu His Gly Tyr Asp wall Ser Gly Ala 165 170 175 same time same time Lys gin wall Ile same time Glu wall Ala Arg Glu Lys Ala gin Leu 180 185 190 Glu Lys Ile same time gin Tyr Tyr Lys Thr Leu Leu gin Asp Lys Glu gin 195 200 205

164

Glu Tyr Thr Thr Arg Lys Asn Asn 210 215 220 Ser same time Arg Ala Gly Tyr gin Met Arg gin Λ .-. Η wall Ile Ser Ser Glu 225 230 2 15 240 Ile Phe Lys same time Gly same time Leu same time Met gin A1, ι Lys Glu Glu Glu wall 245 250 255 Arg Glu Lys Leu gin Glu Glu Arg Glu same time (ϊ 1 u Tyr Leu Arg same time gin 260 265 270 Ile Arg Ser Leu Leu Ser Gly Lys 275 280

(2) INFORMATION ABOUT SEQ. No. 83:

(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)

(A) NAME / KEY: various characters (B) LOCATION 1 ... 393 (xi) SEQUENCE DESCRIPTION: SEQ. No. 83:

Met Arg Lys Leu Phe Ile for Leu Leu Leu Phe Ser Ala Leu Glu Ala 1 5 10 15 same time Glu Lys same time Gly Phe Phe Ile Glu Ala Gly Phe Glu Thr Gly Leu 20 25 30 Leu Glu Gly Thr gin Thr gin Glu Lys Arg His Thr Thr Thr Lys same time 35 40 45 Thr Tyr Ala Thr Tyr same time Tyr Leu for Thr Asp Thr Ile Leu Lys Arg 50 55 60 Ala Ala same time Leu Phe Thr same time Ala Glu Ala Ile Ser Lys Leu Lys Phe 65 70 75 80 Ser Ser Leu Ser for wall Arg wall Leu Tyr Met Tyr same time Gly gin Leu 85 90 95 Thr Ile Glu same time Phe Leu for Tyr same time Leu same time same time wall Lys Leu Ser 100 105 110 Phe Thr Asp Ala gin Gly same time wall Ile Asp Leu Gly wall Ile Glu Thr 115 120 125 Ile for Lys His Ser Lys Ile wall Leu for Gly Glu Ala Phe Asp Ser 130 135 140 Leu Lys Ile Asp for Tyr Thr Leu Phe Leu for Lys Ile Glu Ala Thr 145 150 155 160 Ser Thr Ser Ile Ser Asp Ala same time Thr gin Arg wall Phe Glu Thr Leu 165 170 175 same time Lys Ile Lys Thr same time Leu wall wall same time Tyr Arg same time Glu same time Lys 180 185 190 Phe Lys Asp His Glu same time His Trp Glu Ala Phe Thr for gin Thr Ala 195 200 205 Glu Glu Phe Thr same time Leu Met Leu same time Met Ile Ala wall Leu Asp Ser 210 215 220 gin Ser Trp Gly Asp Ala Ile Leu same time Ala for Phe Glu Phe Thr same time 225 230 235 240 Ser for Thr Asp Cys Asp same time Asp for Ser Lys Cys wall same time for Gly 245 250 255 Thr same time Gly Leu wall same time Ser Lys wall Asp gin Lys Tyr wall Leu same time 260 265 270 Lys gin Asp Ile wall same time Lys Phe Lys same time Lys Ala Asp Leu Asp wall

165

275 280 285 Ile wall Leu Lys Asp Ser Gly wall wall Gly Leu Gly Ser Asp Ile Thr 290 295 300 for Ser same time same time Asp Asp Gly Lys His Tyr Gly gin Leu Gly wall wall 305 310 315 320 Ala Ser Ala Leu Asp for Lys Lys Leu Phe Gly Asp same time Leu Lys Thr 325 330 335 Ile same time Leu Glu Asp Leu Arg Thr Ile Leu His Glu Phe Ser His Thr 340 345 350 Lys Gly Tyr Gly His same time Gly same time Met Thr Tyr gin Arg wall for wall 355 360 365 Thr Lys Asp Gly gin wall Glu Lys Asp Ser same time Gly Lys for Lys Asp 370 375 380 Ser Asp Gly Leu for Tyr same time wall Cys 385 390 (2) INFORMATION 0 SEQ. NO. 8 < 1:

(i, SEQUENCE CHARACTERISTICS:

(A) LENGTH: 270 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 (B7 'LOCATION 1 ... 270 (Xi) SEQUENCE DESCRIPTION: SEQ. No. 84: Met Lys Lys Phe Val Leu Ser G 1 5 10 15 Ser Leu Leu Ala Glu Gly Asp Gly Val Tyr White Gly Thr Asn Tyr Gin 20 25 30 Leu Gly Gin Ala Arg Leu Asn Ser Asn White Tyr Asn Thr Gly Asp Cys 34 40 45 Thr Gly Ser Val Val Gly Cys For Gly Leu Thr Ala Asn Lys His 50 55 60 same time for Gly Gly Thr Asn White Asn Trp His Ser Lys Tyr Ala Asn Gly 65 70 Ala Leu Asn Gly Phe. Gly Leu Asn Val Gly 85 Phe Lys Ser Leu Asp Met Thr 100 105 110 Gly Leu Phe Asp Tyr Gly His 115 120 125 for same time Lys White Gin Leu Asp Met Val Ser Trp Gly Val Gly Ser Asp 130 135 140 Leu Leu Ala Asp White Asp Lys Asp Asn Ala Ser Phe Gly White Phe 145 150 155 160 Gly Gly Val Ala White Gly Gly Asn Thr Trp Lys Ser Ala Ala Asn 165 170 175 Tyr Trp Lys Glu Gin White Glu Ala Lys Gly Pro Asp Val Cys Thr 180 185 190 for Thr Tyr Cys Asn For Asr Ala For Tyr Ser Thr Asn Thr Ser Thr 195 200 205 wall Ala Phe Gin Val Trp Leu Asn 210 215 220 Lys His Asn Gly Val Glu Phe Gly Val Arg Val For Leu Leu Clay Asn

(+420) 225 230 235 240

166

Lys Phe Leu Ser As G Asn Ala Thr Asn Leu Tyr His Leu 245 250 255

Lys Arg Asp Tyr Ser Leu Tyr Leu Gly Tyr Asn Tyr Thr Phe 260 265 270 (2) INFORMATION ABOUT SEQ. No. 85:

(i, SEQUENCE CHARACTERISTICS:

(A, LENGTH: 140 amino acids (B, TYPE: amino acid (D, TOPOLOGY: linear) (ii) MOLECULA TYPE: protein (iii) HYPOTHETICAL: YES (vi, ORIGINAL

(A, ORGANISM: Helicobacter pylori (ix)

(A, NAME / KEY: various characters (B) LOCATION 1 ... 140 (xi, SEQUENCE DESCRIPTION: SEQ ID NO: 85:

Met His for Ile Met Phe Ala Tyr Ile Ala same time Ala I.cu Ala gin Ala 1 5 10 15 Arg Lys Ile same time Gly Thr Leu Cys Met Ala Phe gin Lys Ile Ser gin 20 25 30 wall Lys Glu Leu Gly Ile Asp Lys Ala Lys Ser Leu Ile Gly same time Leu 35 40 45 Ser gin wall Ile Ile Tyr for Thr Lys Asp Thr Asp Glu Leu Ile Glu 50 55 60 Cys Gly wall for Leu Ser Asp Ser Glu Ile same time Phe Leu His same time Thr 65 70 75 80 Asp Met Arg Ala Arg gin wall Leu wall Lys same time Ile wall Thr same time Ala 85 90 95 Ser Ala Phe Ile Glu Ile Asp Leu Lys Lys Ile Cys I.ys same time Tyr Phe 100 105 110 Ile Phe Leu Ile Ala Met Leu wall Ile Glu Lys Ser Ser Met Ile Leu 115 120 125 Lys Lys gin Thr Lys Lys Leu Ile Arg Lys Ser Ile 130 135 140

(2) INFORMATION ABOUT SEQ. No. 86:

(i, SEQUENCE CHARACTERISTICS:

(A) LENGTH: 256 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 ... 256 (xi, SEQUENCE DESCRIPTION: SEQ ID NO: 86:

Met Leu Gly Ser Lys Lys Lys Ala Val Phe

167

Ala Leu Cys Leu Cys Gly Gly Leu Met Ala Glu Gin Asp For Lys Glu 20 25 30 Leu Ile Phe Ser Gly Ile Thr Ile Tyr Thr Asp Lys same time Phe Thr Arg 35 40 45 Ala Lys Lys Tyr Phe Glu Lys Ala Cys Lys Ser same time Asp Ala Asp Gly 50 55 60 Cys Ala Ile Leu Arg Glu wall Tyr Ser Ser Gly Lys Ala Ile Ala Arg 65 70 75 80 Glu same time Ala Arg Glu Ser Ile Glu Lys Ala Leu Glu His Thr Ala Thr 85 90 95 Ala Lys wall Cys Lys Leu same time Asp Ala Glu Lys Cys Lys Asp Leu Ala 100 105 110 Glu Phe Tyr Phe same time wall same time Asp Leu Lys same time Ala Leu Glu Tyr Tyr 115 120 125 Ser Lys Ser Cys Lys Leu same time same time wall Glu Gly Cys Met Leu Ser Ala 130 135 140 Thr Phe Tyr same time Asp Met Ile Lys Gly Leu Lys Lys Asp Lys Lys Asp 145 150 155 160 Leu Glu Tyr Tyr Ser Lys Ala Cys Glu Leu same time same time Gly Gly Gly Cys 165 170 175 Ser Lys Leu Gly Gly Asp Tyr Phe Phe Gly Glu Gly wall Thr Lys Asp 180 185 190 Phe Lys Lys Ala Phe Glu Tyr Ser Ala Lys Ala Cys Glu Leu same time Asp 195 200 205 Ala Lys Gly Cys Tyr Ala Leu Ala Ala Phe Tyr same time Glu Gly Lys Gly 210 215 220 wall Ala Lys Asp Glu Lys gin Thr Thr Glu same time Leu Glu Lys Ser Cys 225 230 235 240 Lys Leu Gly Leu Lys Glu Ala Cys Asp Ile Leu Lys Glu gin Lys gin

245 250 255 (2) INFORMATION ABOUT SEQ. No. 87:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 242 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear

(ii, MOLECULA TYPE: protein Met (iii, HYPOTHETICAL: YES (vi, ORIGINAL SOURCE: (A) ORGANISM: Helicobacter pylori (ix) SIGN: (A) NAME / KEY: different characters (B) LOCATION 1 ... 242 (xi) SEQUENCE DESCRIPTION: SEQ. No. 87: Lys Lys Phe Phe Ser Gin Ser Leu Leu Ala Leu White Clay Ser Met 1 same time 5 10 15 Ala Gly Ser Gly Met Asp Gly Asn Gly Tyr 20 25 30 Leu Gin Gly Gin Ala Gin His His Asp Asp Asn Ser Gin Lys gin 34 40 45 Ala Thr Asn Ala Thr Lys Gly Phe Asp Ala Leu Leu Gly Tyr gin 50 55 60 Phe Phe Glu Lys His Phe Gly Phu Phe Phe 65 Asp 70 Tyr Ala His Ala Asn Ser Lys Leu Lys Asn For Asn Tyr Asn Ser 85 Glu Ala Ala Gin Val Ala Ser Gin White Leu Gly Lys Gin White same time 100 105 110 Arg Leu Thr Asn Ala Ala Pro Arg Thr Phe Glu Pro Asn Met

168

115 120 125 Leu Thr Tyr Gly Gly Ala Met Asp wall Met V.il same time wall Ile same time same time 130 135 140 Gly Ile Met Ser Leu Gly Ala Phe Gly Gly 1 lo gin Leu Ala Gly same time 145 150 1! .5 160 Ser Trp Leu Met Ala Thr for Ser Phe Glu G1 y Ile Leu wall Glu gin 165 170 175 Ala Leu wall Ser Lys Lys Ala Thr Ser Phe r; i n Phe Leu Phe same time wall 180 185 190 Gly Ala Arg Leu Arg Ile Leu Lys His Ser Ser Ile Glu Ala Gly wall 195 200 205 Lys Phe for Met Leu Lys Lys same time for Tyr 1 Ie Thr Ala Lys same time Leu 210 215 220 Asp Ile Gly Phe Arg Arg wall Tyr Ser Trp Tyr wall same time Tyr wall Phe 225 230 2 15 240

Thr Phe (2) SEQ ID NO. No. 88:

(i, SEQUENCE CHARACTERISTICS:

(A) LENGTH: 26 * 7 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 / Kloc: different characters (B, PLACEMENT 1 ... 267

(xi) SEQUENCE DESCRIPTION: SEQ. C.:88:

Met same time Tyr for same time Leu for same time Ser Ala Leu Glu Ile Ser Glu gin 1 5 10 15 for Glu wall Lys Glu Ile Thr same time Glu Leu Leu Lys gin Leu gin same time 20 25 30 Ala Leu Arg Ser same time Ala His Phe Ser Glu gin wall Glu Leu Ser Leu 35 40 45 Lys Cys Ile wall Arg Ile Leu Glu wall Leu Leu Ser Leu Asp Phe Phe 50 55 60 Lys same time Ala same time Glu Ile Asp Ser Ser Leu Arg same time Ser Ile Glu Trp 65 70 75 80 Leu Thr same time Ala Gly Glu Ser Leu Lys Leu Lys Met Lys Glu Tyr Glu 85 90 95 Arg Phe Phe Ser Glu Phe same time Thr Ser Met His Ala same time Glu gin Glu 100 105 110 wall Thr same time Thr Leu same time Ala same time Ala Glu same time Ile Lys Ser Glu Ile 115 120 125 Lys Lys Leu Glu same time gin Leu Ile Glu Thr Thr Thr Arg Leu Leu Thr 130 135 140 Ser Tyr gin Ile Phe Leu same time gin Ala Arg Asp same time Ala same time same time gin 145 150 155 160 Ile Thr Lys same time Lys Thr gin Ser Leu Glu Ala Ile Thr gin Ala Lys 165 170 175 same time same time Ala same time same time Glu Ile Ser same time same time gin Thr gin Ala Ile Thr 180 185 190 same time Ile Thr Glu Ala Lys Thr same time Ala same time same time Glu Ile Ser same time same time 195 200 205 gin Thr gin Ala Ile Thr same time Ile same time Glu Ala Lys Glu Ser Ala Thr 210 215 220

169

Thr Gin Asn Ala Asn Lys Gin Glu Ala Asn Asn Thr Gin

(+420) 225 230 235 240

Glu Lys Thr Glu Ala Thr Ser Glu White Thr Glu Ala Lys Lys Thr Asp

245

His Tyr Gin Asn ile Asp Phe Phe Glu Phe Glu

260 265 (2) INFORMATION ABOUT SEQ. No. 89:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 544 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 ... 544 (xi) SEQUENCE DESCRIPTION: SEQ. No. 89:

wall Ile Glu Thr Ile for Lys His Ser Lys Ile wall Leu for Gly Glu 1 5 10 15 Ala Phe Asp Ser Leu Lys Glu Ala Phe Asp Lys Ile Asp for Tyr Thr 20 25 30 Phe Phe Phe for Lys Phe Glu Ala Thr Ser Thr Ser Ile Ser Asp Thr 35 40 45 same time Thr gin Arg wall Phe Glu Thr Leu same time same time Ile Lys Thr same time Leu 50 55 60 Ile Met Lys Tyr Ser same time Glu same time for same time same time Phe same time Thr Cys for 65 70 75 80 Tyr same time same time same time Gly same time Thr Lys same time Asp Cys Trp gin same time Phe Thr 85 90 95 for gin Thr Ala Glu Glu Phe Thr same time Leu Met Leu same time Met Ile Ala 100 105 110 wall Leu Asp Ser gin Ser Trp Gly Asp Ala Ile Leu same time Ala for Phe 115 120 125 Glu Phe Thr same time Ser Ser Thr Asp Cys Asp Ser Asp for Ser Lys Cys 130 135 140 wall same time for Gly wall same time Gly Arg wall Asp Thr Lys wall Asp gin gin 145 150 155 160 Tyr Ile Leu same time Lys gin Gly Ile Ile same time same time Phe Arg Lys Lys Ile 165 170 175 Glu Ile Asp Ala wall wall Leu Lys same time Ser Gly wall wall Gly Leu Ala 180 185 190 same time Gly Tyr Gly same time Asp Gly Glu Tyr Gly Thr Leu Gly wall Glu Ala 195 200 205 Tyr Ala Leu Asp for Lys Lys Leu Phe Gly same time Asp Leu Lys Thr Ile 210 215 220 same time Leu Glu Asp Leu Arg Thr Ile Leu His Glu Phe Ser His Thr Lys 225 230 235 240 Gly Tyr Gly His same time Gly same time Met Thr Tyr gin Arg wall for wall Thr 245 250 255 Lys Asp Gly gin wall Glu Lys Asp Ser same time Gly Lys for Lys Asp Ser 260 265 270 Asp Gly Leu for Tyr same time wall Cys Ser Leu Tyr Gly Gly Ser same time gin 275 280 285 for Ala Phe for Ser same time Tyr for same time Ser Ile Tyr His same time Cys Ala 290 295 300 Asp wall for Ala Gly Phe Leu Gly wall Thr Ala Ala wall Trp gin gin

170

305 310 315 320

Leu Asn Gin Asn Ala Leu For Ile Asn Tyr Ala Asn Leu Gly Ser 325 330 335 gin Thr same time Tyr same time Leu same time Ala Ser Leu A: n Thr gin Asp Leu Ala 340 345 350 same time Ser Met Leu Ser Thr Ile gin Lys Thr 1 lll! wall Thr Ser Ser wall 355 360 365 Thr same time His His Phe Ser same time Ala Ser gin Si r Phe Arg Ser for Ile 370 375 380 Leu Gly wall same time Ala Lys Ile Gly Tyr gin same time Tyr Phe same time Asp Phe 385 390 1Ί5 400 Ile Gly Leu Ala Tyr Tyr Gly Ile Ile Lys Tyr same time Tyr Ala Lys Ala 405 410 415 wall same time gin Lys wall gin gin Leu Ser Tyr Gly Gly Gly Ile Asp Leu 420 425 430 Leu Leu Asp Phe Ile Thr Thr Tyr Ser same time ·, I.v.: same time Ser for Thr Gly 435 440 445 Ile gin Thr Lys Arg same time Phe Ser Ser Ser I'liľ Gly Ile Phe Gly Gly 450 455 4 60 Leu Arg Gly Leu Tyr same time Ser Tyr Tyr wall Leu same time Lys wall Lys Gly 4 65 470 175 480 Ser Gly same time Leu Asp wall Ala Thr Gly Leu same time Tyr Arg Tyr Lys His 485 4 90 495 Ser Lys Tyr Ser wall Gly Ile Ser Ile for I.ľii Ile gin Arg Lys Ala 500 505 510 Ser wall wall Ser Ser Gly Gly Asp Tyr Thr same time Ser Phe wall Phe same time 515 520 525 Glu Gly Ala Ser His Phe Lys wall Phe Phe same time Tyr Gly Gly Cys Phe

530 535 540 (2, SEQ ID NO: 90:

(i, SEQUENCE CHARACTERISTICS:

(A) LENGTH: 356 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: various: letters (B) POSITION 1, ... 356 (Xi) SEQUENCE DESCRIPTION: SEQ. No. :! 90: Leu Met Lys Ser leu Leu Phe Met Ile Phe wall wall Cys gin Leu 1 5 10 15 Glu Gly Lys Lys Phe Ser Gin Asp same time Phe Lys wall Asp Tyr same time Tyr 20 25 30 Tyr Leu Arg Lys Gin Asp Leu His Ile Ile Lys Thr gin same time Asp Leu 35 40 45 Ser same time Ala Trp Tyr Leu Pro for gin Lys Ala for Lys Glu His Ser 50 55 60 Trp wall Asp Phe Ala Lys Tyr Leu same time Met Met Asp Tyr Leu Gly 65 70 75 80 Thr Tyr Phe Leu For Phe Tyr His Ser Phe Thr for Ile Phe gin Trp 85 90 95 Tyr His Asn Pro Asn Pro Tyr gin Arg same time Glu Phe Lys Phe gin 100 105 110 Ile Ser Phe Arg Val Phe Arg His Tie Leu Trp Thr Lys Gly 115 120 125

171

Thr Leu Tyr Leu Ala Tyr Thr Gin Thr Asn Trp Phe Gin White Tyr Asn 135 140 Asp for gin Ser Ala for Met Arg Met Ile same time Phe Met for Glu Leu 145 150 155 160 Ile Tyr wall Tyr for Ile same time Phe Lys for Phe Gly Gly Lys Ile Gly 165 170 175 same time Phe Ser Glu Ile Trp Ile Gly Trp gin His Ile Ser same time Gly wall 180 185 190 Gly Gly Ala gin Cys Tyr gin for Phe same time Lys Glu Gly same time for Glu 195 200 205 same time gin Phe for Gly gin for wall Ile wall Lys Asp Tyr same time Gly gin 210 215 220 Lys Asp wall Arg Trp Gly Gly Cys Xaa Ser wall Xaa Xaa Gly same time Xaa 225 230 235 240 Leu Cys Phe wall Leu wall Trp Glu Lys Gly Gly Leu Lys Ile Met wall 245 250 255 Ala Tyr Trp for Tyr wall for Tyr Asp gin Ser same time for gin Leu Ile 260 265 270 Asp Tyr Met Gly Tyr Gly same time Ala Lys Ile Asp Tyr Arg Arg Gly Arg 275 280 285 His His Phe Glu Leu gin Leu Tyr Asp Ile Phe Thr gin Tyr Trp Arg 290 295 300 Tyr Asp Arg Trp His Gly Ala Phe Arg Leu Gly Tyr Thr Tyr Arg Ile 305 310 315 320 same time for Phe wall Gly Ile Tyr Ala gin Trp Phe same time Gly Tyr Gly Asp 325 330 335 Gly Leu Tyr Glu Tyr Asp wall Phe Ser same time Arg Ile Gly wall Gly Ile 340 345 350 Arg Leu same time for 355 (2) INFORMATION 0 SEQ. NO. 91

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 675 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 ... 675

(Xi) SEQUENCE DESCRIPTION: SEQ. NO.:! 91: Leu Ser Lys Gly Leu Ser Ile Gly same time Lys Ile Ile Leu Cys wall Ala 1 5 10 15 Leu Ile wall Ile wall Cys wall Ser Ile Leu Gly wall Ser Leu same time Ser 20 25 30 Arg wall Lys Glu Ile Leu Lys Glu Ser Ala Leu His Ser Met gin Asp 35 40 45 Ser Leu His Phe Lys wall Lys Glu wall gin Ser wall Leu Glu same time Thr 50 55 60 Tyr Thr Ser Met Gly Ile wall Lys Glu Met Leu for Glu Asp Thr Lys 65 70 75 80 Arg Glu Ile Lys Ile gin Leu Leu Lys same time Phe Ile Leu Ala same time Ser 85 90 95 His wall Ala Gly wall Ser Met Phe Phe Lys Asp Arg Glu Asp Leu Arg 100 105 110 Leu Thr Leu Leu Arg Asp same time Asp Thr Ile Lys Leu Met Glu same time for

172

115 120 125 Ser Leu Gly Ser same time for Leu Ala gin Lys Ala Met Lys same time Lys Glu 130 135 140 Ile Ser Lys Ser Leu for Tyr Tyr Arg Lys mit for same time Gly Ala Glu 145 150 1!> 5 160 wall Tyr Gly wall Asp Ile Leu Leu for Leu Plio Lys Glu same time Thr gin 165 170 175 Glu wall wall Gly wall Leu Met Ile Phe Phe sow Ile Asp Ser Phe Ser 180 185 190 same time Glu Ile Thr Lys same time Arg Ser Asp Leu Phe Leu Ile Gly wall Lys 195 200 205 Gly Lys wall Leu Leu Ser Ala same time Lys Ser Iifii gin Asp Lys Ser Ile 210 215 220 Thr Glu Ile Tyr Lys Ser wall for Lys Ala Thr same time Glu wall Met Ala 225 230 240 Ile Leu Glu same time Gly Ser Lys Ala Thr Leu Clu Tyr Leu Asp for Phe 245 250 255 Ser His Lys Glu same time Phe Leu Ala wall Glu Thr Phe Lys Met Leu Gly 260 265 270 Lys Thr Glu Ser Lys Asp same time Leu same time Trp Met Ile Ala Leu Ile Ile 275 280 285 Glu Lys Asp Lys wall Tyr Glu gin wall Gly Ser wall Arg Phe wall wall 290 295 300 wall Ala Ala Ser Ala Ile Met wall Leu Ala Leu Ile Ile Ala Ile Thr 305 310 315 320 Leu Leu Met Arg Ala Ile wall Ser same time Arg Leu Glu wall wall Ser Ser 325 330 335 Thr Leu Ser His Phe Phe Lys Leu Leu same time same time gin Ala His Ser Ser 340 345 350 Asp Ile Lys Leu wall Glu Ala Arg Ser same time Asp Glu Leu Gly Arg Met 355 360 365 gin Thr Ala Ile same time Lys same time Ile Leu gin Thr gin Lys Thr Met gin 370 375 380 Glu Asp Arg gin Ala wall gin Asp Thr Ile Lys wall wall Ser Asp wall 385 390 395 400 Lys Ala Gly same time Phe Ala wall Arg Ile Thr Ala Glu for Ala Ser for 405 410 415 Asp Leu Lys Glu Leu Arg Asp Ala Leu same time Gly Ile Met Asp Tyr Leu 420 425 430 gin Glu Ser wall Gly Thr His Met for Ser Ile Phe Lys Ile Phe Glu 435 440 445 Ser Tyr Ser Gly Leu Asp Phe Arg Gly Arg Ile gin same time Ala Ser Gly 450 455 460 Arg wall Glu Leu wall Thr same time Ala Leu Gly gin Glu Ile gin Lys Met 465 470 475 480 Leu Glu Thr Ser Ser same time Phe Ala Lys Asp Leu Ala same time Asp Ser Ala 485 490 495 same time Leu Lys Glu Cys wall gin same time Leu Glu I.ys Ala Ser same time Ser gin 500 505 510 His Lys Ser Leu Met Glu Thr Ser Lys Thr Ile Glu same time Ile Thr Thr 515 520 525 Ser Ile gin Gly wall Ser Ser gin Ser Glu Ala Met Ile Glu gin Gly 530 535 540 Lys Asp Ile Lys Ser Ile wall Glu Ile Ile Arg Asp Ile Ala Asp gin 545 550 555 560 Thr same time Leu Leu Ala Leu same time Ala Ala Ile Glu Ala Ala Arg Ala Gly 565 570 575 Glu His Gly Arg Gly Phe Ala wall wall Ala Asp Glu wall Arg Lys Leu 580 585 590 Ala Glu Arg Thr gin Lys Ser Leu Ser Glu Ile Glu Ala same time Ile same time 595 600 605 Ile Leu wall gin Ser Ile Ser Asp Thr Ser Glu Ser Ile Lys same time gin 610 615 620 wall Lys Glu wall Glu Glu Ile same time Ala Ser Ile Glu Ala Leu Arg Ser 625 630 635 640 wall Thr Glu Gly same time Leu Lys Ile Ala Ser Asp Ser Leu Glu Ile Ser

173

645 650 655

Gin Glu Asp Lys Val Ser Asn Asp Leu Glu Asp Val Asn Lys

660 665 670

Lys Gin Phe 675 (2) SEQ ID NO. No. 92:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 271 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 ... 271 (xi) SEQUENCE DESCRIPTION: SEQ. No. 92:

Met same time Ile Phe Lys Arg Ile Ile Cys wall Thr Ala Ile wall Leu Gly 1 5 10 15 Phe Phe same time Leu Leu Asp Ala Lys His His Lys Glu Lys Lys Glu Asp 20 25 30 His Lys Ile Thr Arg Glu Leu Lys wall Gly Ala same time for wall for His 35 40 45 Ala gin Ile Leu gin Ser wall wall Asp Asp Leu Lys Glu Lys Gly Ile 50 55 60 Lys Leu wall Ile wall Ser Phe Thr Asp Tyr wall Leu for same time Leu Ala 65 70 75 80 Leu same time Asp Gly Ser Leu Asp Ala same time Tyr Phe gin His Arg for Tyr 85 90 95 Leu Asp Arg Phe same time Leu Asp Arg Lys Met His Leu wall Gly Leu Ala 100 105 110 same time Ile His wall Glu for Leu Arg Phe Tyr Ser gin Lys Ile Thr Asp 115 120 125 Ile Lys same time Leu Lys Lys Gly Ser wall Ile Ala wall for same time Asp for 130 135 140 Ala same time gin Gly Arg Ala Leu Ile Leu Leu His Lys gin Gly Leu Ile 145 150 155 160 Ala Leu Lys Asp for Ser same time Leu Tyr Ala Thr Glu Phe Asp Ile wall 165 170 175 Lys same time for Tyr same time Ile Lys Ile Lys for Leu Glu Ala Ala Leu Leu 160 185 190 for Lys wall Leu Gly Asp wall Asp Gly Ala Ile Ile Thr Gly same time Tyr 195 200 205 Ala Leu gin Ala Lys Leu Thr Gly Ala Leu Phe Ser Glu Asp Lys Asp 210 215 220 Ser for Tyr Ala same time Leu wall Ala Ser Arg Glu Asp same time Ala gin Asp 225 230 235 240 Glu Ala Ile Lys Ala Leu Ile Glu Ala Leu gin Ser Glu Lys Thr Arg 245 250 255 Lys Phe Ile Leu Asp Thr Tyr Lys Gly Ala Ile Ile for Ala Phe 260 265 270

(2) INFORMATION ABOUT SEQ. No. 93:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 161 amino acids (B) TYPE: amino acid

174 (D, TOPOLOGY: linear (ii, MOLECULA TYPE: protein (iii, HYPOTHETICAL: YES (vi)) ORIGINAL SOURCE:

(A, ORGANISM: Helicobacter pyJori (ix)

(A) NAME / KEY: various characters (B) LOCATION 1 ... 161 (xi) SEQUENCE DESCRIPTION: SEQ. No. 93:

Met Phe Phe Lys Thr Tyr gin Lys Leu Leu Cl y Ala Ser Cys Leu Ala 1 5 10 15 Leu Tyr Leu wall Gly Cys Gly same time Gly Gly C! S Gly Glu Ser for wall 20 25 30 Glu Met Ile Ala same time Ser Glu Gly Thr Phe C1 n Ile Asp Ser Lys Ala 35 40 45 Asp Ser Ile Thr Ile gin Gly wall Lys Leu A :: n Arg Gly same time Cys Ala 50 55 60 wall same time Phe wall for wall Ser Glu Thr Phe gin Met Gly wall Leu Ser 65 70 75 80 gin wall Thr for Ile Ser Ile gin Asp Phe Lys Asp Met Ala Ser Thr 85 90 95 Tyr Lys Ile Phe Asp gin Lys Lys Gly Leu Ala same time Ile Ala same time Lys 100 105 110 Ile Ser gin Leu Glu gin Lys Gly wall Met Met Glu for gin Thr Leu 115 120 125 same time Phe Gly Glu Ser Leu Lys Gly Ile Ser gin Gly Cys same time Ile Ile 130 135 140 Glu Ala Glu Ile gin Thr Asp Lys Gly Ala Trp Thr Phe same time Phe Asp 145 150 155 160

Lys (2) INFORMATION ABOUT SEQ. No. 94:

(i, SEQUENCE CHARACTERISTICS:

(A) LENGTH: 337 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 ... 337 (xi) SEQUENCE DESCRIPTION: SEQ. No. 94:

Met Ile Arg Leu Lys Gly Leu same time Lys Thr Leu Lys Thr Ser Leu Leu 1 5 10 15 Ala Gly wall Leu Leu Gly Ala Thr Ala for Leu Met Ala Lys for Leu 20 25 30 Leu Ser Asp Glu Asp Leu Leu Lys Arg wall Lys Leu His same time Ile Lys 35 40 45 Glu Asp Thr Leu Thr Ser Cys same time Ala Lys wall Asp Gly Ser gin Tyr 50 55 60

175

Leu same time Ser Gly Trp same time Leu Ser Lys Glu Phe for gin Glu Tyr Arg 65 70 75 80 Glu Lys Ile Phe Glu Cys wall Glu Glu Glu Lys His Lys gin Ala Leu 85 90 95 same time Leu Ile same time Lys Glu Asp Thr Glu Asp Lys Glu Glu Leu Ala Lys 100 105 110 Lys Ile Lys Glu Ile Lys Glu Lys Ala Lys wall Leu Arg gin Lys Phe 115 120 125 Met Ala Phe Glu Met Lys Glu His Ser Lys Glu Phe for same time Lys Lys 130 135 140 gin Leu gin Thr Met Leu Glu same time Ala Phe Asp same time Gly Ala Glu Ser 145 150 155 160 Phe Ile Asp Asp Trp His Glu Arg Phe Gly Gly Ile Ser Arg Glu same time 165 170 175 Thr Tyr Lys Ala Leu Gly Ile Lys Glu Tyr Ser Asp Glu Gly Lys Ile 180 185 190 Leu Ala Phe Gly Glu Arg Ser Tyr Ile Arg gin Tyr Lys Lys Asp Phe 195 200 205 Glu Glu Ser Thr Tyr Asp Thr Arg gin Thr Leu Ser Ala Met Ala same time 210 215 220 Met Ser Gly Glu same time Asp Tyr Lys Ile Thr Trp Leu Lys for Lys Tyr 225 230 235 240 gin Leu His Ser Ser same time same time Ile Lys for Leu Met Ser same time Thr Glu 245 250 255 Leu Leu same time Met Ile Glu Leu Thr same time Ile Lys Lys Glu Tyr wall Met 260 265 270 Gly Cys same time Met Glu Ile Asp Gly Ser Lys Tyr for Ile His Lys Asp 275 280 285 Trp Gly Phe Phe Gly Lys Ala Lys wall for Glu Thr Trp Arg same time Lys 290 295 300 Ile Trp Glu Cys Ile Lys same time Lys wall Lys Ser Tyr Asp same time Thr Thr 305 310 315 320 Ala Glu Ile Gly Ile wall Trp Lys Lys same time Thr Tyr Ser Ile Ser His 325 330 335

His (2) SEQ ID NO. No. 95:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 416 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 ... 416

(xi) SEQUENCE DESCRIPTION: SEQ. No. 95:

Met Lys Lys Leu wall Phe Ser Met Leu Leu Cys Cys Lys Ser wall Phe 1 5 10 15 Ala Glu Gly Glu Thr for Leu Ile wall same time Asp for Glu Thr His wall 20 25 30 Ser gin Ala Thr Ile Ile Gly Lys Met wall Asp Ser Ile Lys Arg Tyr 35 40 45 Glu Glu Ile Ile Ser Lys Ala gin Ala gin wall same time gin Leu gin Lys 50 55 60 wall same time same time Met Ile same time Thr Thr same time Ser Leu Ile Ser Ser Ser Ala

176

65 70 75 80 Ile Thr Leu Ala same time for Met gin wall Leu gin same time Ala gin Tyr gin 85 90 95 Ile Glu Ser Ile Arg Tyr same time Tyr Glu same time Leu Lys gin Ser Ile Glu 100 105 110 same time Trp same time Ala gin same time Leu Leu Arg same time Lys Tyr Leu gin gin gin 115 120 125 Cys for Trp Leu same time wall same time Ala Leu Thr same time same time Lys Ile wall same time 130 135 140 Leu Lys Asp Leu same time same time Leu Ile Thr Lys same time Gly Glu gin Thr gin 145 150 155 160 Thr Ala Arg Asp wall gin same time Leu Ile gin Ser Ile Ser Gly Ser Gly 165 170 175 Tyr Gly same time Met gin Ser Leu Ala Gly Glu Leu Ser Gly Arg Ala Trp 180 185 190 Gly Glu Met Leu Cys Lys Met wall same time Asp Ser same time Tyr Glu Ser Glu 195 200 205 gin Ala Leu Leu Ala Thr Gly same time same time for Glu Glu gin Lys Arg Arg 210 215 220 Phe Leu Leu Arg wall Lys Lys Lys wall same time Asp Asri I.ys gin Leu Lys 225 230 235 240 Asp Lys Leu Asp for Phe Leu Lys Arg Leu Asp wall Leu gin Thr Glu 245 250 255 Phe Gly wall Thr Asp for Thr Ala same time His same time Lys gin Gly Ile His 260 265 270 Tyr Cys Thr Glu same time Lys Glu Thr Gly Lys Cys Asp for Ile Lys same time 275 280 285 wall Phe Arg Thr Thr Arg Leu Asp same time Glu Leu Glu gin Glu Ile gin 290 295 300 Thr Leu Thr Leu Asp Leu Ile Lys Ala Ser same time Lys Asp Ala gin Ser 305 310 315 320 gin Ala Tyr Ala same time Phe same time gin Arg Ile Lys Leu Leu Thr Leu Lys 325 330 335 Tyr Leu Lys Glu Ile Thr same time gin Met Leu Phe Leu same time gin Thr Met 340 345 350 Ala Met gin Ser Glu Ile Met Thr Asp Asp Tyr Phe Arg gin same time same time 355 360 .165 Asp Gly Phe Gly Glu Lys Glu same time His Ile Asp Lys gin Leu Thr gin 370 375 380 Lys Arg Ile same time Glu Arg Glu Arg Ala Arg Ile Tyr Phe gin same time for 385 390 395 400 same time wall Lys Phe Asp gin Phe Gly Phe for Ile Phe Ser Ile Trp Asp 405 410 415

(2) INFORMATION ABOUT SEQ. No. 96:

(i, SEQUENCE CHARACTERISTICS:

(A) LENGTH: 376 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 ... 376 (xi) SEQUENCE DESCRIPTION: SEQ. No. 96:

Lys Gly Ala Lys Gly Ala Val Val Phly Ala Gly Phe Ala 15 10 15

177

Thr Thr Thr Thr Phe 20 Ser Leu ile Tyr His Gin 25 Lys Pro Lys Ala for Leu same time same time gin for Ser Leu Leu same time Asp Asp Glu wall Lys Tyr for 35 40 45 Leu gin Asp Tyr Thr Phe Thr gin same time for gin for Thr same time Thr Glu 50 55 60 Ser Ser Lys Asp Ala Thr Ile Lys Ala Leu gin Glu gin Leu Lys Ala 65 70 75 80 Ala Leu Lys Ala Leu same time Ser Lys Glu Met same time Tyr Ser Lys Glu Glu 85 90 95 Thr Phe Thr Ser for for Met Asp for Lys Thr Thr for for Lys Lys 100 105 110 Asp Phe Ser for Lys gin Leu Asp Leu Leu Ala Ser Arg Ile Thr for 115 120 125 Phe Lys gin Ser for Lys same time Tyr Glu Glu same time Leu Ile Phe for wall 130 135 140 Asp same time for same time Gly Ile Asp Ser Phe Thr same time Leu Lys Glu Lys Asp 145 150 155 160 Ile Ala Thr same time Glu same time Lys Leu Leu Arg Thr Ile Thr Ala Asp Lys 165 170 175 Met Ile for Ala Phe Leu Ile Thr for Ile Ser Ser gin Ile Ala Gly 180 185 190 Lys wall Ile Ala gin wall Glu Ser Asp Ile Phe Ala Ser Met Gly Lys 195 200 205 Ala wall Leu Ile for Lys Gly Ser Lys wall Ile Gly Tyr Tyr Ser same time 210 215 220 same time same time Lys Met Gly Glu Tyr Arg Leu Asp Ile wall Trp Ser Arg Ile 225 230 235 240 Ile Thr for His Gly Ile same time Ile Met Leu Thr same time Ala Lys Gly Ala 245 250 255 Asp Ile Lys Gly Tyr same time Gly Leu wall Gly Glu Leu Ile Glu Arg same time 260 265 270 Phe gin Arg Tyr Gly wall for Leu Leu Leu Ser Thr Leu Thr same time Gly 275 280 285 Leu Leu Ile Gly Ile Thr Ser Ala Leu same time same time Arg Gly same time Lys Glu 290 295 300 Glu wall Thr same time Phe Phe Gly Asp Tyr Leu Leu Leu gin Leu Met Arg 305 310 315 320 gin Ser Gly Met Gly Ile same time gin wall wall same time gin Ile Leu Arg Asp 325 330 335 Lys Ser Lys Ile Ala for Ile wall wall Ile Arg Glu Gly Ser Arg wall 340 345 350 Phe Ile Ser for same time Thr Asp Ile Phe Phe for Ile for Arg Glu same time 355 360 365 Glu wall Ile Ala Glu Phe Leu Lys 370 375

(2) INFORMATION ABOUT SEQ. No. 97:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 916 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 ... 916 (xi) SEQUENCE DESCRIPTION: SEQ. No. 97:

178

wall Asp Leu Arg Ile gin Ser Lys Glu wall Ser His same time Leu Lys Glu 1 5 10 15 Leu Ser Lys Thr Leu Ile Ser Tyr for Phe G1 u Lys His wall Glu Ala 20 25 30 Leu Gly Glu gin Cys Ser same time Phe wall Ser J le for Ile same time same time Asp 35 40 45 Asp Tyr Ser same time Ile Cys Thr Phe wall Ser A :: p Phe Ile same time Leu Ile 50 55 60 Ala Ser Tyr same time Leu Leu Glu Ser Phe Leu Λί-.ρ Phe Tyr Lys Asp Lys 65 70 7! I 80 Leu Lys Leu Ser Glu Leu wall Thr Glu Tyr Ala same time wall Thr same time same time 85 90 95 Leu Leu Phe Lys Lys Leu Ile Lys His Leu Ser Gly same time same time gin Leu 100 105 110 wall Lys same time Phe Tyr gin Cys Ile Arg Glu 11 »! Ile Lys Tyr same time Ala 115 120 125 for same time Lys Glu Tyr Lys for same time gin Phe I'lic Ile Ile Gly Lys Gly 130 135 140 Lys gin Lys gin Leu Ala Lys Ile Tyr Ser H i .‘i Leu Lys Glu Leu Ser 145 150 1!>!> 160 Ala Ser Glu Ile Lys for gin Asp Met Glu Asp Ile Leu Lys Lys Leu 165 170 175 Glu Glu Leu Asp Lys Ile Phe Lys Thr Thr Asp Phe Thr Lys Phe Thr

180 185 190

For Lys Thr Glu White Lys Asp White Lys Glu White Asp Glu White Lys Tyr 195 200 205

Asn Glu Asn Phys Lys Arg Gin Phe Asn Glu Asph Glu Ser Asn 210 215 220 White Glu Lys His Asp Glu White Lys Lys Asp Phe Arg Asn Lys Glu 225 230 235 240

Ser Leu clay Arg Glu clay Glu Asn His Cys Lys Asn Ser 245 250 255 Glu Glu Glu for Glu Tyr Lys Ile same time Asp Leu Leu Lys same time Ile gin 260 265 270 gin Ile Cys Lys same time Tyr Ile Glu Ser His Ala wall same time Asp wall Ser 275 280 285 Lys Asp Ile Lys Ser Met Met Cys gin Phe Tyr Leu Lys gin Ile Asp 290 295 300 Leu Leu wall same time Ser Glu Ile wall Arg Tyr Arg Tyr Ser same time Leu Phe 305 310 315 320 Glu for Ile gin Arg Ser Leu Trp Glu Ser Ile Lys Ile Leu Asp same time 325 330 335 Glu Ser Gly Ile Tyr Leu Phe for Lys same time Ile Gly Glu Ile Lys Asp 340 345 350 Lys Phe Glu Ala same time Lys Glu Lys Phe Lys gin Ser Lys same time wall Ser 355 360 365 Glu Phe Ala Glu Tyr Cys Arg Glu Cys same time for Tyr Thr Ala Phe same time 370 375 380 Phe His Leu same time Ile same time same time Gly Leu Ser His gin Phe Glu Lys Phe 385 390 395 400 wall for Ile Met Lys Glu Tyr Lys Glu for Lys Ile Thr Asp same time Asp 405 410 415 Leu Glu Ala Ile Ser Thr Lys Glu Thr Gly Leu Ala Ser gin Leu Ser 420 425 430 Gly His Trp Phe Phe gin Leu Ser Leu Phe same time Lys Thr same time Phe same time 435 440 445 for same time Lys Ile Trp Ile for Leu Glu Phe same time Lys Arg Ser Lys Ile 450 455 460 Lys Phe Asp Lys Asp Leu Glu Ile Tyr Phe Asp Ser His Glu Ser Phe 465 470 475 480 same time Ile Ser Lys Lys Tyr Leu gin Glu Ile Asp gin Glu Ser Leu Lys 485 490 495 Lys Ile Lys gin Ser Lys Asp Phe Phe Ser Ile gin Lys Ile Glu Ser 500 505 510 Lys His Asp same time same time Asp Ile Leu gin Leu Glu Phe Phe Glu same time Asp

179

Thr Ser 515 Phe Leu same time 530 Met gin Leu 545 Leu Leu Ala Ile Ile Arg wall Arg His Glu Ile 580 Lys same time Glu 595 for Ile Phe 610 same time Phe Met 625 Phe same time His same time Ser wall for Ala His Lys same time 660 His wall Asp 675 Thr Asp Glu 690 Gly Ser wall 705 Ser Lys Asp Ser Gly gin His wall Glu Gly Ile 740 Thr Arg Tyr 755 Lys Glu Ile 770 Ser Gly Leu 785 Lys Leu Cys Glu Arg Lys Cys wall Ala same time Glu 820 Glu Cys Asp 835 Arg His Arg 850 same time Lys Tyr 865 Lys Thr Arg Leu Lys Arg same time Phe Leu Ile Lys 900 same time 915

Phe Ala Lys 520 Gly Lys Ile 535 Asp Ser wall 550 gin Asp Ser 565 His same time same time Lys Leu Glu wall Tyr Ile Leu Ser 600 gin Phe Gly 615 Phe Leu Ile 630 Ile Tyr wall 645 Arg Lys Glu Phe wall Thr Phe wall His Leu Asp 680 Glu Ile Lys 695 same time His Asp 710 Ala Leu Asp 725 Phe His same time for Asp Tyr Cys Tyr Tyr Lys Asp 760 same time Lys same time 775 Asp Ser Leu 790 Asp same time His 805 Phe same time gin gin Met His Asp for Phe Lys gin 840 Ile Ala Lys 855 same time Lys Leu 870 Tyr Gly Gly 885 Leu Lys Leu Phe

Ser Phe Ala Glu Leu Ile Thr 540 Lys for gin 555 Asp Ser Leu 570 for Arg Glu 585 Asp Cys Arg Lys gin Ser Thr Gly Tyr same time wall 620 Gly Met Asp 635 Glu for Arg 650 Lys Phe Leu 665 Leu Ala Thr His Ile Arg Ile wall Phe same time Tyr 700 for Lys Ile 715 Lys Arg gin 730 Lys His Arg 745 Leu Ser Ala Phe for Ile for Phe same time Asp Met 780 Lys for Ile 795 wall Leu Ala 810 Thr Ser Glu 825 Ile Thr Ile Leu Glu Asp Cys Phe gin Met Glu 860 Leu Glu Asp 875 Ala Ile Lys 890 Trp Ile Ala

905

525 White Leu Glu Tyr

Glu Phe Asn Lys 560

Tyr Gin Leu Lys 576

Lys Tyr Thr Glu 590

Ser His Asp 605

Phe Gin Trp Ala

Ser His Phe Ser 640

Ala Thr His Leu 655

Lys Glu Tyr Ala 670

Asp Pro Phe Leu 686

Glu Lys Glu Thr

Leu Asn Asn Ala 720

Ser Leu Gly Val 735 White Phe Val 750

Lys Leu Tyr Leu 764

Thr Phe Leu

Glu Thr White Glu 800

Thr Asp Asp Asp 815

Arg Phe Lys Arg 831

Gin Leu Ser Asp 845

Ser Ala Asn Asp

Ser Met Ala Phe 879

Glu Lys Gin Thr 896

Trp Ala Thr Asn 910 (2, SEQ ID NO: 98:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 176 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULA TYPE: protein (iii, HYPOTHETICAL: YES (vi, ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori

180 (ix) SIGN:

(A) NAME / KEY: various characters (B, LOCATION 1 ... 176 (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 98:

Met Thr Ala Met Met Arg Tyr Phe His Ile Tyr Ala Thr Thr Phe Phe 1 5 10 15 Phe for Leu Ala Leu Leu Phe Ala wall Ser Gly Leu Ser Leu Leu Phe 20 25 30 Lys Ala Arg gin Asp Thr Gly Ala Lys Ile Lys Glu Trp wall Leu Glu 35 40 15 Lys Ser Leu Lys Lys Glu Glu Arg Leu Asp Phe Leu l.ys Gly Phe Ile 50 55 60 Lys Glu same time His Ile Ala Met for Lys Lys Ile Glu LRO Arg Glu Tyr 65 70 75 80 Arg Gly Ala Leu wall Ile Gly Thr for Leu Tyr Glu Ile same time Leu Glu 85 90 95 Thr Lys Gly Thr gin Thr Lys Ile Lys Thr Ile Glu Arg Gly Phe Leu 100 105 110 Gly Ala Leu Ile Met Leu His Lys Ala Lys wall Gly Ile wall Phe gin 115 120 125 Ala Leu Leu Gly Ile Phe Cys wall Phe Leu Leu Leu Phe Tyr Leu Ser 130 135 140 Ala Phe Leu Met wall Ala Phe Lys Asp Thr Lys Arg Met Phe Ile Ser 145 150 155 160 wall Leu Ile Gly Ser wall wall Phe Phe Gly Ala Ile Tyr Trp Ser Leu

165 170 175 (2, SEQ ID NO: 99:

(i, SEQUENCE CHARACTERISTICS:

(A) LENGTH: 222 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) LOCATION. ... 222 (Xi. SEQUENCE DESCRIPTION: SEQ. No. :! 99: Met Phe Lys Asn Ala Leu same time Ile gin Asp Phe Ser Phe Lys same time His 1 5 10 15 Thr Ser Thr Ala ile ile Gly Thr same time Gly Ala Gly Lys Ser Thr Leu 20 25 30 Ile same time Thr White Leu Gly Ile Arg Ser Asp Tyr same time Phe Lys Ala gin 35 40 45 same time same time Asn For Pro Tyr His Asp same time wall Ile for gin Arg Lys gin 50 55 60 Leu Gly Val Val Ser Asn Leu Phe same time Tyr for for Gly Leu same time Ala 65 70 75 80 same time Asp Leu Phe Tyr gin Phe Phe His Lys same time Cys Thr Leu 85 90 95 Asp Leu Phe Glu Lys Asn Leu Leu same time Lys Thr Tyr Glu His Leu Ser 100 105 110 Asp Gly Gin Lys Gin Arg Leu Lys Ile Asp Leu Ala Leu Ser His His 115 120 125 for gin Leu Val ile Met Asp Glu for Glu Thr Ser l.eu Glu gin same time

181

130 135 140 Ala Leu Ile Arg Leu Ser same time Leu Ile Ser Leu Arg same time Thr gin 145 150 155 Leu Thr Ser Ile Ile Ala Thr His Asp for Ile wall Leu Asp Ser 165 170 175 Glu Trp wall Leu Leu Leu Lys same time Gly same time Ile Ala gin Tyr Lys 180 185 190 Leu same time Ser Ile Leu Lys Ser wall Ala Lys Thr Phe same time Phe Lys 195 200 205 Lys for Thr Thr Lys Asp Leu Leu Ala Leu Leu Lys Asp Ile 210 215 220

gin

160

Cys

for

Glu (2) INFORMATION ABOUT SEQ. NO. 100:

(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 / Kloc: different characters (B) PLACEMENT 1 ... 406

(xi) SEQUENCE DESCRIPTION: SEQ. NO. 100:

Met Tyr Ala Ala His for Ile Lys for Ile Lys Ala for Lys Leu Lys 1 5 10 15 Ser gin Phe Leu Arg Arg wall Phe wall Gly Ala Ser Ile Arg Arg Trp 20 25 30 same time Asp gin Ala cys for Leu Glu Phe wall Glu Leu Asp Lys gin Ala 35 40 45 His Lys Ala Met Ile Ala Tyr Leu Leu Ala Lys Asp Leu Lys Asp Arg 50 55 60 Gly Lys Asp Leu Asp Leu Asp Leu Leu Ile Lys Tyr Phe Cys Phe Glu 65 70 75 80 Phe Leu Glu Arg Leu wall Leu Thr Asp Ile Lys for for Ile Phe Tyr 85 90 95 Ala Leu gin gin Thr His Ser Lys Glu Leu Ala Ser Tyr wall Ala gin 100 105 110 Ser Leu gin Asp Glu Ile Ser Ala Tyr Phe Ser Leu Glu Glu Leu Lys 115 120 125 Glu Tyr Leu Ser His Arg for gin Ile Leu Glu Thr gin Ile Leu Glu 130 135 140 Ser Ala His Phe Tyr Ala Ser Lys Trp Glu Phe Asp Ile Ile Tyr His 145 150 155 160 Phe same time for same time Met Tyr Gly wall Lys Glu Ile Lys Asp Lys Ile Asp 165 170 175 Lys gin Leu His same time same time Asp His Leu Phe Glu Gly Leu Phe Gly Glu 180 185 190 Lys Glu Asp Leu Lys Lys Leu wall Ser Met Phe Gly gin Leu Arg Phe 195 200 205 gin Lys Arg Trp Ser gin Thr for Arg wall for gin Thr Ser wall Leu 210 215 220 Gly His Thr Leu Cys wall Ala Ile Met Gly Tyr Leu Leu Ser Phe Asp 225 230 235 240 Leu Lys Ala Cys Lys Ser Met Arg Ile same time His Phe Leu Gly Gly Leu 245 250 255 Phe His Asp Leu for Glu Ile Leu Thr Arg Asp Ile Ile Thr for Ile 260 265 270

182

Lys Gin Ser Val Ala Gly Leu Asp His Cys White Lys Glu Ile Glu Lys 275 280 285 Lys Glu Met gin same time Lys wall Tyr Ser Phe wall Ser Lil ' Gly wall gin 290 295 300 Glu Asp Leu Lys Tyr Phe Thr Glu same time Glu Phe Lys same time Arg Tyr Lys 305 310 315 320 Asp Lys Ser His gin Ile wall Phe Thr Lys Asp Ala Clu Glu Leu Phe 325 330 335 Thr Leu Tyr same time Ser Asp Glu Tyr Leu Gly wall Cys Gly Glu Leu Leu 340 345 350 Lys wall Cys Asp His Leu Ser Ala Phe Leu Glu Ala gin Ile Ser Leu 355 360 165 Ser His Gly Ile Ser Ser Tyr Asp Leu Ile gin Gly Ala Lys same time Leu 370 375 380 Leu Glu Leu Arg Ser gin Thr Glu Leu Leu asd Leu A :: p Leu Gly Lys 385 390 39 * 5 400 Leu Phe Arg Asp Phe Lys 405

(2) INFORMATION ABOUT SEQ. NO. 101:

(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 SIGN: (A, NAME / KEY: different characters (B, PLACEMENT 1 ... 335

(xi, SEQUENCE DESCRIPTION: SEQ. 0: 101:

wall Leu Trp wall Leu Tyr Phe Leu Thr Ser Leu Phe Ile Cys Ser Leu 1 5 10 15 Ile wall Leu Trp Ser Lys Lys Ser Met Leu Phe wall Asp same time Ala same time 20 25 30 Lys Ile gin Gly Phe His His Ala Arg Thr for Arg Ala Gly Gly Leu 35 40 45 Gly Ile Phe Leu Ser Phe Ala Leu Ala Cys Tyr Leu Glu for Phe Glu 50 55 60 Met for Phe Lys Gly for Phe wall Phe Leu Gly Leu Ser Leu wall Phe 65 70 75 80 Leu Ser Gly Phe Leu Glu Asp Ile same time Leu Ser Leu Ser for Lys Ile 85 90 95 Arg Leu Ile Leu gin Ala wall Gly wall wall Cys Ile Ile Ser Ser Thr 100 105 110 for Leu wall wall Ser Asp Phe Ser for Leu Phe Ser Leu for Tyr Phe 115 120 125 Ile Ala Phe Leu Phe Ala Ile Phe Met Leu wall Gly Ile Ser same time Ala 130 135 140 Ile same time Ile Ile Asp Gly Phe same time Gly Leu Ala Ser Gly Ile Cys Ala 145 150 155 160 Ile Ala Leu Leu wall Ile His Tyr Ile Asp for Ser Ser Leu Ser Cys 165 170 175 Leu Leu Ala Tyr Met wall Leu Gly Phe Met wall Leu same time Phe for Ser 180 185 190 Gly Lys Ile Phe Leu Gly Asp Gly Gly Ala Tyr Phe Leu Gly Leu wall 195 200 205 Cys Gly Ile Ser Leu Leu His Leu Ser Leu Glu gin Lys Ile Ser wall

183

210 215 220 Phe Phe Gly Leu same time Leu 'Met Leu Tyr for wall Ile Glu wall Leu Phe 225 230 235 240 Ser Ile Leu Arg Arg Lys Ile Lys Arg gin Lys Ala Thr Met for Asp 245 250 255 same time Leu His Leu His Thr Leu Leu Phe Lys Phe Leu gin gin Arg Ser 260 265 270 Phe same time Tyr for same time for Leu Cys Ala Phe Ile Leu Ile Leu Cys same time 275 280 285 Leu for Phe Ile Leu Ile Ser wall Leu Phe Arg Leu Asp Ala Tyr Ala 290 295 300 Leu Ile wall Ile Ser Leu wall Phe Ile Ala Cys Tyr Leu Ile Gly Tyr 305 310 315 320 Ala Tyr Leu same time Arg gin wall Cys Ala Leu Glu Lys Arg Ala Phe 325 330 335

(2, SEQ ID NO: 102:

(i, SEQUENCE CHARACTERISTICS:

(A) LENGTH: 96 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 ... 96 (xi) SEQUENCE DESCRIPTION: SEQ. NO.: 102:

Met Lys Lys wall Ile wall Ala Leu Gly wall Leu Ala Phe Ala same time wall 1 5 10 15 Leu Met Ala Thr Asp wall Lys Ala Leu wall Lys Gly Cys Ala Ala Cys 20 25 30 His Gly wall Lys Phe Glu Lys Lys Ala Leu Gly Lys Ser Lys Ile wall 35 40 45 same time Met Met Ser Glu Lys Glu Ile Glu Glu Asp Leu Met Ala Phe Lys 50 55 60 Ser Gly Ala same time Lys same time for wall Met Thr Ala gin Ala Lys Lys Leu 65 70 75 80 Ser Asp Glu Asp Ile Lys Ala Leu Ala Lys Tyr Ile for Thr Leu Lys 85 90 95

(2) INFORMATION ABOUT SEQ. NO. 103:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 156 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: various characters (B) LOCATION 1 ... 156

184 (xi) SEQUENCE DESCRIPTION: SEQ. NO. 103:

Met Arg Asp Phe 1 same time Ala wall Phe 20 Ala Ile Ser 35 Gly Leu Leu 50 Gly Ala wall 65 Glu Leu Ile Arg Glu Asp Glu Lys Thr Arg Tyr 100 Lys Ala Leu 115 Leu Ser gin 130 same time Glu Tyr 145 Ile gin same time

Asn Asn White Gin 5 Glu Lys Leu Asp Ala Ser Gly wall 40 Phe Gly Leu 55 Lys Ala for 70 Phe Leu His 85 Glu for Leu Phe Leu same time gin Lys Gly Leu Ile 120 Leu same time Asp 135 Ile Lys same time 150 Arg Arg

Thr Arg 10 Glu Phu Leu Lys wall 25 Gly Lys Ser Glu Ser same time Ala 60 Asp Thr Glu 75 Glu wall Ile 90 Ser wall Thr 105 Ser Leu Ser Lys Arg Leu Ser Leu Met Leu Ser 140 Leu Ala for 155 Phe

Val Arg Gin 15

Ρ: Gl Gl Leu Ser 30 '

Leu il Ala Ser 15

Ser Asn Glu

Tyr Gly White Phe 80! I e Lvs Lys Glu 95

l.ys Asn Thr Leu

Arg :: η Asp Arg Phe l.! 5

l.eu Leu Asp Gly (2) SEQ ID NO. NO. 104:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 118 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 ... 118 (xi) SEQUENCE DESCRIPTION: SEQ. NO. 104:

wall Met Leu Met Ala Ile Phe Thr for Tyr Ile Leu Ile Leu Lys Met 1 5 10 15 Met Lys Lys Ser Met Ser Leu Phe Ala same time Met Gly Leu Glu gin Ile 20 25 30 Phe Cys same time Arg Asp Ile Lys Asp Leu same time Asp Phe wall Phe Gly Ile 35 40 45 Glu wall Gly Leu Asp Ser same time Ala Arg Lys same time Arg Ser Arg Lys Ala 50 55 60 Met Glu same time His Leu Ile Gly Leu Phe wall gin Ala gin Leu same time Phe 65 70 75 80 Lys Glu gin wall Asp Ile Arg Glu Phe Glu Asp Leu Arg gin Ala Phe 85 90 95 Gly same time Asp Thr Lys Lys Phe Asp Phe wall Ile Phe Ser Lys Glu Lys 100 105 110 Thr Tyr Phe His Arg Ser 115

(2) INFORMATION ABOUT SEQ. NO. 105:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 355 amino acids (B) TYPE: amino acid

185 (D) TOPOLOGY: linear (ii) MOLECULA TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori SIGN: (A) NAME / KEY: different characters (B) PLACEMENT 1 ... 355

(xi) SEQUENCE DESCRIPTION: SEQ. NO. 105:

Met same time Ile Lys Ile Leu Lys Ile Leu wall Gly Gly Leu Phe Phe Leu 1 5 10 15 Ser Leu same time Ala His Leu Trp Gly Lys gin Asp same time Ser Phe Leu Gly 20 25 30 Ile Gly Glu Arg Ala Tyr Lys Ser Gly same time Tyr Ser Lys Ala Ala Ser 35 40 45 Tyr Phe Lys Lys Ala Cys same time Asp Gly wall Ser Glu Gly Cys Thr gin 50 55 60 Leu Gly Ile Ile Tyr Glu same time Gly gin Gly Thr Arg Ile Asp Tyr Lys 65 70 75 80 Lys Ala Leu Glu Tyr Tyr Lys Thr Ala Cys gin Ala Asp Asp Arg Glu 85 90 95 Gly Cys Phe Gly Leu Gly Gly Leu Tyr Asp Glu Gly Leu Gly Thr Ala 100 105 110 gin same time Tyr gin Glu Ala Ile Asp Ala Tyr Ala Lys Ala Cys wall Leu 115 120 125 Lys His for Glu Ser Cys Tyr same time Leu Gly Ile Ile Tyr Asp Arg Lys 130 135 140 Ile Lys Gly same time Ala Ala gin Ala wall Thr Tyr Tyr gin Lys Ser Cys 145 150 155 160 same time Phe Asp Met Ala Lys Gly Cys Tyr Ile Leu Gly Thr Ala Tyr Glu 165 170 175 Lys Gly Phe Leu Glu wall Lys gin Ser same time His Lys Ala wall Ile Tyr 180 185 190 Tyr Leu Lys Ala Cys Arg Leu same time Glu Gly gin Ala Cys Arg Ala Leu 195 200 205 Gly Ser Leu Phe Glu same time Gly Asp Ala Gly Leu Asp Glu Asp Phe Glu 210 215 220 wall Ala Phe Asp Tyr Leu gin Lys Ala Cys Ala Leu same time same time Ser Gly 225 230 235 240 Gly Cys Ala Ser Leu Gly Ser Met Tyr Met Leu Gly Arg Tyr wall Lys 245 250 255 Lys Asp for gin Lys Ala Phe same time Tyr Phe Lys gin Ala Cys Asp Met 260 265 270 Gly Ser Ala wall Ser Cys Ser Arg Met Gly Phe Met Tyr Ser gin Gly 275 280 285 Asp Thr wall Ser Lys Asp Leu Arg Lys Ala Leu Asp same time Tyr Glu Arg 290 295 300 Gly Cys Asp Met Gly Asp Glu wall Gly Cys Phe Ala Leu Ala Gly Met 305 310 315 320 Tyr Tyr same time Met Lys Asp Lys Glu same time Ala Ile Met Ile Tyr Asp Lys 325 330 335 Gly Cys Lys Leu Gly Met Lys gin Ala Cys Glu same time Leu Thr Lys Leu 340 345 350

Arg Gly Tyr 355 (2) SEQ ID NO. NO. 106:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 193 amino acids

186 (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 ... 193 (xi) SEQUENCE DESCRIPTION: SEQ. NO. 106:

Met Lys Glu Lys same time Phe Trp for Leu Gly Ile Met :; <* R wall Leu Ile 1 5 10 15 Phe Gly Leu Gly Ile wall wall Phe Leu wall wall PHF. · Ala Leu Lys same time 20 25 30 Ser for Lys same time Asp Leu wall Tyr Phe Lys Gly His A: $ n Glu wall Asp 35 40 45 Leu same time Phe same time Ala Met Leu Lys Thr Tyr Glu same time The Lys Ser same time 50 55 60 Tyr Arg Phe Ser wall Gly Leu Lys for Leu Thr Glu Ser for Lys Thr 65 70 75 80 for Ile Leu for Tyr Phe Ser Lys Gly Thr His Gly Asp Lys Lys Ile 85 90 95 gin Glu same time Leu Leu same time same time Ala Leu Ile Leu Glu Lys Ser same time Thr 100 105 110 Leu Tyr Ala gin Leu gin for Leu Lys for Ala Leu Asp Ser for same time 115 120 125 Ile gin wall Tyr Leu Ala Phe Tyr for Ser gin Ser gin for Arg Leu 130 135 140 Leu Gly Thr Leu Asp Cys Lys same time Ala Cys Glu for Leu Lys Phe Asp 145 150 155 160 Leu Leu Glu Gly Asp Lys wall Gly Arg Tyr Lys Ile Leu Phe Lys Phe 165 170 175 wall Phe Lys same time Lys Glu Glu Leu Ile Leu Glu gin Leu Ala Phe Phe 180 185 190

Lys (2) INFORMATION ABOUT SEQ. NO. 107:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 289 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 ... 289

(Xi) DESCRIPTION; SEQUENCE: SEQ. NO .: 107: Leu Gly Asn Met Cys Ser Lys Lys Ile Arg same time Leu Ile Leu Cys 1 5 10 15 Phe Gly Phe ile Leu Ser Leu Cys Ala Glu Glu same time Ile Thr Lys Glu

187

20 25 30 same time Met Thr Glu Thr same time Thr Thr Glu Glu same time Thr for Lys Asp Ala 35 40 45 for Ile Leu Leu Glu Glu Lys Arg Ala gin Thr Leu Glu Leu Lys Glu 50 55 60 Glu same time Glu wall Ala Lys Lys Ile Asp Glu Lys Ser Leu Leu Glu Glu 65 70 75 80 Ile His Lys Lys Lys Arg gin Leu Tyr Met Leu Lys Gly Glu Leu His 85 90 95 Glu Lys same time Glu Ser Ile Leu Phe gin gin Met Ala Lys same time Lys Ser 100 105 110 Gly Phe Phe Ile Gly wall Ile Leu Gly Asp Ile Gly Ile same time Ala same time 115 120 125 for Tyr Glu Lys Phe Glu Leu Leu Ser same time Ile gin Ala Ser for Leu 130 135 140 Leu Tyr Gly Leu Arg Ser Gly Tyr gin Lys Tyr Phe Ala same time Gly Ile 145 150 155 160 Ser Ala Leu Arg Phe Tyr Gly Glu Tyr Leu Gly Gly Ala XET Lys Gly 165 170 15 Phe Lys Ser Asp Ser Leu Ala Ser Tyr gin Thr Ala Ser Leu same time Ile 180 185 190 Asp Leu Leu Met Asp Lys for Ile Asp Lys Glu Lys Arg Phe Ala Leu 195 200 205 Gly Ile Phe Gly Gly wall Gly wall Gly Trp same time Gly Met Tyr gin same time 210 215 220 Leu Lys Glu Ile Arg Gly Tyr Ser gin for same time Ala Phe Gly Leu wall 225 230 235 240 Leu same time Leu Gly wall Ser Met Thr Leu same time Leu Lys His Arg Phe Glu 245 250 255 Leu Ala Leu Lys Met for for Leu Lys Glu Thr Ser gin Thr Phe Leu 260 265 270 Tyr Tyr Phe Lys Ser Thr same time Ile Tyr Tyr Ile Ser Tyr same time Tyr Leu 275 280 285 Leu

(2) INFORMATION 0 SEQ. NO. 108: (I) SEQUENCE CHARACTERISTICS: (A) LENGTH: 668 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (Ii. MOLECULA TYPE: protein (Iii) HYPOTHETICAL: YES (See, ORIGINAL SOURCE: (A) ORGANISM: Helicobacter pylori (Ix, SIGN: (A) NAME / KEY: different characters (B) LOCATION 1 ... 668 (Xi. SEQUENCE DESCRIPTION: SEQ. No. :: L08: Met Arg Lys Leu Phe White For Leu Leu Leu Phe Ser Ala Leu Glu Ala 1 5 10 15 same time Glu Lys Asn Gly Phe Phe White Glu Ala Gly Phe Glu Thr Gly Leu 20 25 30 Leu Glu Gly Thr Gin Arg His Thr Thr Thr Lys same time 35 40 45 Thr Tyr Ala Thr Tyr Asn Tyr Leu Thr Asp Thr Ile Leu Lys Arg 50 55 60 Ala Ala Asn Leu Phe Thr Asn Ala Glu Ala Ile Ser Lys Leu Lys Phe 65 70 75 80

188

Ser Ser Leu Ser for wall Arg wall Leu Tyr Met Tyr same time Gly gin Leu 85 90 95 Thr Ile Glu same time Phe Leu for Tyr same time Leu same time same time wall Lys Leu Ser 100 105 110 Phe Thr Asp Ala gin Gly same time Thr Ile Asp Leu Gly V.il Ile Glu Thr 115 120 125 Ile for Lys His Ser Lys Ile wall Leu for Gly Glu Ala Phe Asp Ser 130 135 140 Leu Lys Glu Ala Phe Asp Lys Ile Asp for Tyr Thr Leu Phe Leu for 145 150 155 160 Lys Phe Glu Ala Thr Ser Thr Ser Ile Ser Asp Thr same time Thr gin Arg 165 170 175 wall Phe Glu Thr Leu same time same time Ile Lys Thr same time Leu Ilo Met Lys Tyr 180 185 190 Ser same time Glu same time for same time same time Phe same time Thr Cys for Tyr same time same time same time 195 200 20 f. Gly same time Thr Lys same time Asp Cys Trp gin same time Phe Thr Pi o gin Thr Ala 210 215 220 Glu Glu Phe Thr same time Leu Met Leu same time Met Ile Ala wall Leu Asp Ser 225 230 235 240 gin Ser Trp Gly Asp Ala Ile Leu same time Ala for Phe Glu Phe Thr same time 245 250 255 Ser Ser Thr Asp Cys Asp Ser Asp for Ser Lys Cys wall same time for Gly 260 265 270 wall same time Gly Arg wall Asp Thr Lys wall Asp gin gin Tyr Ile Leu same time 275 280 285 Lys gin Gly Ile Ile same time same time Phe Arg Lys Lys Ile Glu Ile Asp Ala 290 295 300 wall wall Leu Lys same time Ser Gly wall wall Gly Leu Ala same time Gly Tyr Gly 305 310 315 320 same time Asp Gly Glu Tyr Gly Thr Leu Gly wall Glu Ala Tyr Ala Leu Asp 325 330 335 for Lys Lys Leu Phe Gly same time Asp Leu Lys Thr Ile same time Leu Glu Asp 340 345 350 Leu Arg Thr Ile Leu His Glu Phe Ser His Thr Lys Gly Tyr Gly His 355 360 365 same time Gly same time Met Thr Tyr gin Arg wall for wall Thr Lys Asp Gly gin 370 375 380 wall Glu Lys Asp Ser same time Gly Lys for Lys Asp Ser Asp Gly Leu for 385 390 395 400 Tyr same time wall Cys Ser Leu Tyr Gly Gly Ser same time gin for Ala Phe for 405 410 415 Ser same time Tyr for same time Ser Ile Tyr His same time Cys Ala Asp wall for Ala 420 425 430 Gly Phe Leu Gly wall Thr Ala Ala wall Trp gin gin Leu Ile same time gin 435 440 445 same time Ala Leu for Ile same time Tyr Ala same time Leu Gly Ser gin Thr same time Tyr 450 455 460 same time Leu same time Ala Ser Leu same time Thr gin Asp Leu Ala same time Ser Met Leu 4 65 470 475 480 Ser Thr Ile gin Lys Thr Phe wall Thr Ser Ser wall Thr same time His His 485 490 495 Phe Ser same time Ala Ser gin Ser Phe Arg Ser for Ile Leu Gly wall same time 500 505 510 Ala Lys Ile Gly Tyr gin same time Tyr Phe same time Asp Phe Ile Gly Leu Ala 515 520 525 Tyr Tyr Gly Ile Ile Lys Tyr same time Tyr Ala Lys Ala wall same time gin Lys 530 535 540 wall gin gin Leu Ser Tyr Gly Gly Gly Ile Asp Leu Leu Leu Asp Phe 545 550 555 560 Ile Thr Thr Tyr Ser same time Lys same time Ser for Thr Gly Ile gin Thr Lys 565 570 575 Arg same time Phe Ser Ser Ser Phe Gly Ile Phe Gly Gly Leu Arg Gly Leu 580 585 590 Tyr same time Ser Tyr Tyr wall Leu same time Lys wall Lys Gly Ser Gly same time Leu

595

600

605

189

Asp Val Ala Thr Gly Leu same time Tyr Arg Tyr Lys His Ser Lys Tyr Ser 610 615 620 wall Gly ile Ser Ile for Leu Ile gin Arg Lys Ala Ser wall wall Ser 625 630 635 640 Ser Gly Gly Asp Tyr Thr same time Ser Phe wall Phe same time Glu Gly Ala Ser 645 650 655 His Phe Lys wall Phe Phe same time Tyr Gly Trp wall Phe 660 665

(2) INFORMATION ABOUT SEQ. NO. 109:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 63 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 ... 63 (xi) SEQUENCE DESCRIPTION: SEQ. NO. 109:

Met same time Thr Glu Ile Leu Thr Ile Met Leu wall wall Ser wall Leu Met 1 5 10 15 Gly Leu wall Gly Leu Ile Ala Phe Leu Trp Gly wall Lys Ser Gly gin 20 25 30 Phe Asp Asp Glu Lys Arg Met Leu Glu Ser wall Leu Tyr Asp Ser Ala 35 40 45 Ser Asp Leu same time Glu Ala Ile Leu gin Glu Lys Arg gin Lys same time 50 55 60

(2) INFORMATION ABOUT SEQ. NO. 110:

(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)

(A) NAME / KEY: various characters (B) LOCATION 1 ... 406 (xi) SEQUENCE DESCRIPTION: SEQ. NO. 110:

Met wall Phe Phe His Lys Lys Ile Ile Leu same time Phe Ile Tyr Ser Leu 1 5 10 15 Met wall Ala Phe Leu Phe His Leu Ser Tyr Gly wall Leu Leu Lys Ala 20 25 30 Asp Gly Met Ala Lys Lys gin Thr Leu Leu wall Gly Glu Arg Leu wall 35 40 45 Trp Asp Lys Leu Thr Leu Leu Gly Phe Leu Glu Lys same time His Ile for 50 55 60

190

gin Lys Leu Tyr Tyr Asn Le Ser Ser Gin Asp Lys Glu Leu Ser Ala 65 70 75 80 Glu Ile gin Ser same time wall Thr Tyr Tyr Thr Leu Arq Asp Ala same time same time 85 90 95 Thr Leu Ile gin Ala Leu Ile for Ile Ser gin Asp l.eu gin Ile His 100 105 110 Ile Tyr Lys Lys Gly Glu Asp Tyr Phe Leu Asp Phu 1 le for Ile wall 115 120 125 Phe Thr Arg Lys Glu Arg Thr Leu Leu Leu Ser Leu gin Thr Ser for 130 135 140 Tyr gin Asp Ile wall Lys Ala Thr same time Asp for Leu Leu Ala same time gin 145 150 155 160 Leu Met same time Ala Tyr Lys Lys Ser wall for Phe Ly :: Arq Leu wall Lys 165 170 175 same time Asp Lys Ile Ala Ile wall Tyr Thr Arg Asp Tyr Ai g wall Gly gin 180 185 190 Ala Phe Gly gin for Thr Ile Lys Met Ala Met wall Í'.IT Ser Arg Leu 195 200 : Ί:? Ι His gin Tyr Tyr Leu Phe Ser His Ser same time Gly Arg you: Tyr Asp Ser 210 215 220 Lys Ala gin Glu wall Ala Gly Phe Leu Leu Glu Thr LRO wall Lys Tyr 225 230 235 240 Thr Arg Ile Ser Ser for Phe Ser Tyr Gly Arg Phe His for wall Leu 245 250 255 Lys wall Lys Arg for His Tyr Gly wall Asp Tyr Ala aid Lys His Gly 260 265 270 Ser Leu Ile His Ser Ala Ser Asp Gly Arg wall Gly Phe Ile Gly wall 275 280 285 Lys Ala Gly Tyr Gly. Lys wall wall Glu Ile His Leu same time Glu Leu Arg 290 295 300 Leu wall Tyr Ala His Met Ser ' Ala Phe Ala same time Gly Leu Lys Lys Gly 305 310 315 320 Ser Phe wall Lys Lys Gly gin Ile Ile Gly Arg wall Gly Ser Thr Gly 325 330 335 Leu Ser Thr Gly for His Leu His Phe Gly wall Tyr Lys same time Ser Arg 340 345 350 for Ile same time for Leu Gly Tyr Ile Arg Thr Ala Lys Ser Lys Leu His 355 360 365 Gly Lys gin Arg Glu wall Phe Leu Glu Lys Ala gin Tyr Ser Lys gin 370 375 380 Lys Leu Glu Glu Leu Phe Lys Thr His Ser Phe Glu Lys same time Ser Phe 385 390 395 400 Tyr Leu Leu Glu Gly Phe 405 (2) SEQ ID NO. No. 5.:111:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 296 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 ... 296 (xi) SEQUENCE DESCRIPTION: SEQ. NO. 111:

Leu Phe Leu Val Lys Lys White Gly Val Val White Met. Leu Val Cys

191

10 15

Phe Leu Ala Cys Ser Gin Glu Ser Phe White Lys Met Gin Lys Lys Ala

25 30

Gin Glu Asn Asp Gly Ser Lys Arg Pro Ser Tyr Val Asp Ser

40 45

Asp Tyr Glu Val Phe Ser Glu Thr Phe Leu Gin Asn Met Val Tyr

55 60

Gin Pro Glu Glu Arg Asn Ala Phe Phe Gin Leu Thr Lys Asp Glu

70

Asp Asn Ser Phe Asn Pro Glu Asn Ser Val White Leu Leu Asn Glu Pro

90 95

Ser Asp Asn Ser Glu Lys Asn Leu Leu Ser Tyr Pro Asn Asp Pro Asn

100 105 110

Asn Gn Asp Asn Ala Asn Asn Ser Gin Lys Asn Pro Phe Leu Tyr

115 120 125

Lys For Lys Arg Lys Thr Lys Asn For Lys Leu White Glu Tyr Ser Gin

129 135 140

Gin Asp Phe Tyr Pro Leu Lys Asn Gly Asp White Met Ser Lys Glu

145 150 155 160

Gly Asp Gin Trp Leu White Glu White Gin Ser Lys Ala Leu Lys Arg Phe

165 170 175

Leu Lys Asp Gin Asn Asp Lys Asp Arg Gin White Gin Thr Phe Thr Phe

180 185 190

Asn Asp Thr Lys Thr Gin White Ala Gin White Lys Gly Lys White Ser Ser

195 200 205

Tyr Val Thr Thr Thr Asn Asn Gly Ser Leu

210 215 220

Glu Ser Phe Leu Glu Lys Lys Ser Asp Asn Val Tyr Thr Glu

(+420) 225 230 235 240

Asn Lys Ala Leu Asp Thr Met Glu White Ser Lys Cys Gin Met Val Leu

245

Lys Lys His Ser Thr Asp Lys Leu Asp Ser Gin His Lys Ala White Ser

260 265 270 íle Asp Asp Leu Ph Ph Phe Lys Lys Glu

275 280 285

Phe Leu Lys Glu Cys Leu Lys Glu Ser

290 295 (2) INFORMATION 0 SEQ. No .: 112:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 248 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 ... 248 (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 112:

wall Ser Tyr Asp same time Thr Asp Asp Tyr Tyr Phe for Arg same time Gly wall 1 5 10 15 Ile Phe Ser Ser Tyr Ala Thr Met Ser Gly Leu for Ser Ser Gly Thr 20 25 30 Leu same time Ser Trp same time Gly Leu Gly Gly same time wall Arg same time Thr Lys wall 35 40 45 Tyr Gly Lys Phe Ala Ala Tyr His His Leu gin Lys Tyr Leu Leu Ile 50 55 60

192

Asp Leu Ile Ala Arg Phe Lys Thr gin Gly Gly Tyr Ile Phe Arg Tyr 65 70 75 80 same time Thr Asp Asp Tyr Leu for Leu same time Ser Thr Phe Tyr Met Gly Gly 85 90 95 wall Thr Thr wall Arg Gly Phe Arg same time Gly Ser Ile Thr for Lys Asp 100 105 110 Glu Phe Gly Leu Trp Leu Gly Gly Asp Gly Ile Phe Thr Ala Ser Thr 115 120 125 Glu Leu Ser Tyr Gly wall Leu Lys Ala Ala Lys Met Arg Leu Ala Trp 130 135 140 Phe Phe Asp Phe Gly Phe Leu Thr Phe Lys Thr for Thr Arg Gly Ser 145 150 155 160 Phe Phe Tyr same time Ala for Thr Thr Thr Ala same time Phe I.ys Asp Tyr Gly 165 170 175 wall wall Gly Ala Gly Phe Glu Arg Ala Thr Trp Arq A! A Ser Thr Gly 180 185 190 Leu gin Ile Glu Trp Ile Ser for Met Gly for only V.il Leu Ile Phe 195 200 / 05 for Ile Ala Phe Phe same time gin Trp Gly Asp Gly same time G'.y Lys Lys Cys 210 215 220 Lys Gly Leu Cys Phe same time for same time Met same time Asp Tyr '' n r gin His Phe 225 230 235 240 Glu Phe Ser Met Gly Thr Arg Phe 245

(2) INFORMATION ABOUT SEQ. NO. 113:

(1) 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) SIGN: (A) NAME / KEY: different characters (B) PLACEMENT 1 ... 335

(xi) SEQUENCE DESCRIPTION: SEQ. NO. 113:

wall 1 Gin His Phe Asn Phe Leu Tyr Lys Asp Ser Leu Phe Ser Ala Ala 10 15 Leu Phe Thr Phe Ile Ile Ala Leu wall Ile Leu Leu Glu gin Ala Arg 20th 25 30 Ala Tyr Phe Thr Arg Lys Arg same time Lys Lys Phe Leu gin Lys Phe Ala 35 40 45 gin same time gin same time Ala Tyr Ala Ser Ser Glu same time Leu Asp Glu Leu Leu 50 55 60 Lys His Ala Lys Ile Ser Ser Leu Met Phe Leu Ala Arg Ala Tyr Ser 65 70 75 80 Lys Ala Asp wall Glu Met Ser Ile Glu Ile Leu Lys Gly Leu Leu same time 85 90 95 Arg for Leu Lys Asp Glu Glu Lys Ile Ala wall Leu Asp Leu Leu Ala 100 105 110 Lys same time Tyr Phe Ser wall Gly Tyr Leu gin Lys Thr Lys Asp Thr wall 115 120 125 Lys Glu Ile Leu Arg Phe Ser for Arg same time wall Glu Ala Leu Leu Lys 130 135 140 Leu Leu His Ala Tyr Glu Leu Glu Lys Asp Tyr Ser Lys Ala Leu Glu 145 150 155 160 Thr Leu Glu Cys Leu Glu Glu Leu Glu wall for Lys 1 le Glu Thr Ile

193

165 170 175

Lys Asn Tyr Leu Tyr Leu Met His Leu White Glu Asn Lys Glu Asp Ala

180 185 190

Ala Lys White Leu His Val Ser Lys

195 200 205

Ala Leu Asn His Leu Lys Ser His Asp Glu Asn Leu Phe Trp Gin Glu

210 215 220 Asp Asp Thr Thr Glu Arg Leu Glu Asn Val Asp Asp Leu Trp Asp

(+420) 225 230 235 240

Met Asnals For Ala Phe I Leu Glu Lys His Ala Leu Leu Gin Asp

245 250 255 Ala Arg Ser Gin Gly Leu Leu Leu Asp His Lys Pro Cys Gin White

260 265 270

Phe Glu Leu Glu Val Leu Arg Ala Leu Leu His Ser Pro Lys Ala

275 280 285

Ser Leu Thr Phe Glu Tyr Arg Cys Lys His Cys Lys Gin White Phe Pro

290 295 300

Phe Glu Ser His Arg. Cys Pro Val Cys Tyr Gin Leu Ala Phe Met Asp 305 310 315 320

Met Val Leu Lys Ser Ser Lys Lys Thr His Ala Met Gly Val Asp

325 330 335 (2) INFORMATION ABOUT SEQ. NO. 114:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 413 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 ... 413 (xi) SEQUENCE DESCRIPTION: SEQ. NO. 114:

Met Arg Lys Ile Phe Ser Tyr Ile Ser Lys wall Leu Leu Phe Ile Gly 1 5 10 15 wall wall Tyr Ala Glu for Asp Ser Lys wall Glu Ala Leu Glu Gly Arg 20 25 30 Lys gin Glu Ser Ser Leu Asp Lys Lys Ile Arg gin Glu Leu Lys Ser 35 40 45 Lys Glu Leu Lys same time Lys Glu Leu Lys same time Lys Asp Leu Lys same time Lys 50 55 60 Glu Glu Lys Lys Glu Thr Lys Ala Lys Arg Lys for Arg Ala Glu wall 65 70 75 80 His His Gly Asp Ala Lys same time for Thr for Lys Ile Thr for for Lys 85 90 95 Ile Lys Gly Ser Ser Lys Gly wall gin same time gin Gly wall gin same time same time 100 105 110 Ala for Lys for Glu Glu Lys Asp Thr Thr for gin Ala Thr Glu Lys 115 120 125 same time Lys Glu Thr Ser for Ser Ser gin Phe same time Ser Ile Phe Gly same time 130 135 140 for same time same time Ala Thr same time same time Thr Leu Glu Asp Lys wall wall Gly Gly 145 150 155 160 Ile Ser Leu Leu wall same time Gly Ser for Ile Thr Leu Tyr gin Ile gin 165 170 175 Glu Glu gin Glu Lys Ser Lys wall Ser Lys Ala gin Ala Arg Asp Arg 180 185 190

194

Leu Al Ala Glu Lys Asn 200 gin Glu White Glu Arg 205 Leu Lys Ile 195 His wall Asp Asp Asp Lys Leu Asp gin Glu Met Ala Mnt Met Ala gin 210 215 220 gin gin Gly Met Asp Leu Asp His Phe Lys gin Met Leu Met Ala Glu 225 230 235 240 Gly His Tyr Lys Leu Tyr Arg Asp gin Leu Lys Glu His Leu Glu Met 245 250 255 gin Glu Leu Leu Arg same time Ile Leu Leu Thr same time wall Asp Thr Ser Ser 260 265 270 Glu Thr Lys Met Arg Glu Tyr Tyr same time Lys His Lys Clu gin Phe Ser 275 280 ? H5 Ile for Thr Glu Ile Glu Thr wall Arg Tyr Thr Ser Thr same time gin Glu 290 295 300 Asp Leu Glu Arg Ala Met Ala Asp for same time Leu Glu Vul for Gly wall 305 310 315 320 Ser Lys Ala same time Glu Lys Ile Glu Met Lys Thr Leu Ann for gin Ile 325 330 335 Ala gin wall Phe Ile Ser His Glu gin Gly Ser Phe Thr for wall Met 340 345 350 same time Gly Gly Gly Gly gin Phe Ile Thr Phe Tyr Ile Lys Glu Lys Arg 355 360 365 Gly Lys same time Glu wall Ser Phe Ser gin Ala Lys gin Phe Ile Ala gin 370 375 380 Lys Leu wall Glu Glu Ser Lys Asp Lys Ile Leu Glu Glu His Phe Glu 385 390 395 400 Lys Leu Arg wall Lys Ser Arg Ile wall Met Ile Arg Glu

405 410 (2, SEQ ID NO: 115:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 186 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) LOCATION 1 ... 186 (xi, SEQUENCE DESCRIPTION: SEQ ID NO: 115: Metys Lys Args Ala Cyss Leu Ser Leu Ser Ala Ser Leu Ala 15 10 15 Leu Ala Gly Glu Val Asn Gly Phe Met Gly Ala Gly Tyr Gin Gin 20 25 30 Gly Arg Tyr Gly For Tyr Asn Ser 34 40 45 Asn Asp Leu Tyr Gly Leu 50 55 60 Asn Lys Trp Phe Gly Ala Arg Val Tyr Gly Phe Leu Asp Trp Phe Asn 65 70 75 80 Thr Ser Gly Thr Glu His Thr Lys Thr Asn Leu Thr Tyr Gly Gly 85 Gly Gly Asp Leu Clay Val Asn Leu Clay For Leu Asp Lys Phe Ala Leu 100 105 110 Gly Leu White Gly Gly Val Gin Leu Ala Gly Asn Thr Trp Met Phe Pro 115 120 125 Tyr Asp Asn Gin Thr Arg Phe Gin Phu Leu Trp Asn Gly Gly

195

130 135 140 Arg Met Arg wall Gly Asp Arg Ser Ala Phe Glu Ala Gly wall Lys Phe 145 150 155 160 for Met wall same time gin Gly Ser Lys Asp wall Gly Leu Ile Arg Tyr Tyr 165 170 175 Ser Trp Tyr wall Asp Tyr wall Phe Thr Phe 180 185

(2) INFORMATION ABOUT SEQ. NO. 116:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 242 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 .. .242

(xi) SEQUENCE DESCRIPTION: SEQ. NO. 116:

Met Lys Lys Phe Phe 5 Ser Gin Ser Leu Leu Ala Leu Ile 10 Ile Ser 15 Met same time Ala wall Ser Gly Met Asp Gly same time Gly wall Phe Leu Gly Ala Gly 20 25 30 Tyr Leu gin Gly gin Ala gin Met His Ala Asp Ile same time Ser gin Lys 35 40 45 gin Ala Thr same time Ala Thr Ile Lys Gly Phe Asp Ala Leu Leu Gly Tyr 50 55 60 gin Phe Phe Phe Glu Lys His Phe Gly Leu Arg Leu Tyr Gly Phe Phe 65 70 75 80 Asp Tyr Ala His Ala same time Ser Ile Lys Leu Lys same time for same time Tyr same time 85 90 95 Ser Glu Ala Ala gin wall Ala Ser gin Ile Leu Gly Lys gin Glu Ile 100 105 110 same time Arg Leu Thr same time Ile Ala Asp for Arg Thr Phe Glu for same time Met 115 120 125 Leu Thr Tyr Gly Gly Ala Met Asp wall Met wall same time wall Ile same time same time 130 135 140 Gly Ile Met Ser Leu Gly Ala Phe Gly Gly Ile gin Leu Ala Gly same time 145 150 155 160 Ser Trp Leu Met Ala Thr for Ser Phe Glu Gly Ile Leu wall Glu gin 165 170 175 Ala Leu wall Ser Lys Lys Ala Thr Ser Phe gin Phe Leu Phe same time wall 180 185 190 Gly Ala Arg Leu Arg Ile Leu Lys His Ser Ser Ile Glu Ala Gly wall 195 200 205 Lys Phe for Met Leu Lys Lys same time for Tyr Ile Thr Ala Lys same time Leu 210 215 220 Asp Ile Gly Phe Arg Arg wall Tyr Ser Trp Tyr wall same time Tyr wall Phe 225 230 235 240

Thr Phe (2) SEQ ID NO. NO. 117:

(i, SEQUENCE CHARACTERISTICS:

(A) LENGTH: 256 amino acids (B) TYPE: amino acid

196 (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. .256

(xi) SEQUENCE DESCRIPTION: SEQ. NO. 117:

Met Gly Tyr Ala Ser Lys Leu Ala Leu Lys Ile Cys L> '11 wall Gly Leu 1 5 10 15 Cys Leu Phe Ser Thr Leu Gly Ala Glu His Leu Glu g i u Lys Gly same time 20 25 30 Tyr Ile Tyr Lys Gly Glu Glu Ala Tyr same time same time Lys g: u Tyr Glu Arg 35 40 4!) Ala Ala Ser Phe Tyr Lys Ser Ala Ile Lys same time Gly Glu Ser Leu Ala 50 55 60 Tyr Ile Leu Leu Gly Ile Met Tyr Glu same time Gly Arg f. '. s wall for Lys 65 70 75 80 Asp Tyr Lys Lys Ala wall Glu Tyr Phe gin Lys Ala V.iL Asp same time Asp 85 90 95 Ile for Arg Gly Tyr same time same time Leu Gly wall Met Tyr Lys Glu Gly Lys 100 105 110 Gly wall for Lys Asp Glu Lys Lys Ala wall Glu Tyr Phe Arg Ile Ala 115 120 125 Thr Glu Lys Gly Tyr Thr same time Ala Tyr Ile same time Leu Gly Ile Met Tyr 130 135 140 Met Glu Gly Arg Gly wall for Ser same time Tyr Ala Lys Ala Thr Glu Cys 145 150 155 160 Phe Arg Lys Ala Met His Lys Gly same time wall Glu Ala Tyr Ile Leu Leu 165 170 175 Gly Asp Ile Tyr Tyr Ser Gly same time Asp gin Leu Gly Ile Glu for Asp 180 185 190 Lys Asp Lys Ala wall wall Tyr Tyr Lys Met Ala Ala Asp wall Ser Ser 195 200 205 Ser Arg Ala Tyr Glu Gly Leu Ser Glu Ser Tyr Arg Tyr Gly Leu Gly 210 215 220 wall Glu Lys Asp Lys Lys Lys Ala Glu Glu Tyr Met gin Lys Ala Cys 225 230 235 240 Asp Phe Asp Ile Asp Lys same time Cys Lys Lys Lys same time Thr Ser Ser Arg 245 250 255

(2) INFORMATION ABOUT SEQ. NO. 118:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 657 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 ... 657

197 (xi) SEQUENCE DESCRIPTION: SEQ. NO. 118:

Met Arg Lys Leu Phe Ile for Leu Leu Leu Phe Ser Ala Leu Glu Ala 1 5 10 15 same time Glu Lys same time Gly Phe Phe Ile Glu Ala Gly Phe Glu Thr Gly Leu 20 25 30 Leu Glu Gly Thr gin Thr gin Glu Lys Arg His Thr Thr Thr Lys same time 35 40 45 Thr Tyr Ala Thr Tyr same time Tyr Leu for Thr Asp Thr Ile Leu Lys Arg 50 55 60 Ala Ala same time Leu Phe Thr same time Ala Glu Ala Ile Ser Lys Leu Lys Phe 65 70 75 80

Ser Ser Leu Ser Pro Val Ar Val Leu Tyr Met Tyr Asn Gly Gin Leu 85 90 95

Thr ile Glu Asn Phe Leu For Tyr Asn Leu Asn Asn Val Lys Leu Ser 100 105 110

Phe Thr Asp Ala Gin Gly Asn Val White Asp Leu Gly Val White Glu Thr 115 120 125 White Pro Lys His Ser Lys White Val Leu Pro Gly Ala Phe Asp Ser 130 135 140

Leu Lys Ile Asp for Tyr Thr Leu Phe Leu for Lys Ile Glu Ala Thr 145 150 155 160 Ser Thr Ser Ile Ser Asp Ala same time Thr gin Arg wall Phe Glu Thr Leu 165 170 175 same time Lys Ile Lys Thr same time Leu wall wall same time Tyr Arg same time Glu same time Lys 180 185 190 Phe Lys Asp His Glu same time His Trp Glu Ala Phe Thr for gin Thr Ala 195 200 205 Glu Glu Phe Thr same time Leu Met Leu same time Met Ile Ala wall Leu Asp Ser 210 215 220 gin Ser Trp Gly Asp Ala Ile Leu same time Ala for Phe Glu Phe Thr same time 225 230 235 240 Ser for Thr Asp Cys Asp same time Asp for Ser Lys Cys wall same time for Gly 245 250 255 Thr same time Gly Leu wall same time Ser Lys wall Asp gin Lys Tyr wall Leu same time 260 265 270 Lys gin Asp Ile wall same time Lys Phe Lys same time Lys Ala Asp Leu Asp wall 275 280 285 Ile wall Leu Lys Asp Ser Gly wall wall Gly Leu Gly Ser Asp Ile Thr 290 295 300 for Ser same time same time Asp Asp Gly Lys His Tyr Gly gin Leu Gly wall wall 305 310 315 320 Ala Ser Ala Leu Asp for Lys Lys Leu Phe Gly Asp same time Leu Lys Thr 325 330 335 Ile same time Leu Glu Asp Leu Arg Thr Ile Leu His Glu Phe Ser His Thr 340 345 350 Lys Gly Tyr Gly His same time Gly same time Met Thr Tyr gin Arg wall for wall 355 360 365 Thr Lys Asp Gly gin wall Glu Lys Asp Ser same time Gly Lys for Lys Asp 370 375 380 Ser Asp Gly Leu for Tyr same time wall Cys Ser Leu Tyr Gly Gly Ser same time 385 390 395 400 gin for Ala Phe for Ser same time Tyr for same time Ser Ile Tyr His same time Cys 405 410 415 Ala Asp wall for Ala Gly Phe Leu Gly wall Thr Ala Ala wall Trp gin 420 425 430 gin Leu Ile same time gin same time Ala Leu for Ile same time Tyr Ala same time Leu Gly 435 440 445 Ser gin Thr same time Tyr same time Leu same time Ala Ser Leu same time Thr gin Asp Leu 450 455 460 Ala same time Ser Met Leu Ser Thr Ile gin Lys Thr Phe wall Thr Ser Ser 4 65 470 475 480 wall Thr same time His His Phe Ser same time Ala Ser gin Ser Phe Arg Ser for 485 490 495 Ile Leu Gly wall same time Ala Lys Ile Gly Tyr gin same time Tyr Phe same time Asp 500 505 510

198

Phe Gly Leu Ala Tyr Tyr Gly White Lys Tyr Asn Tyr Ala Lys 515 520 525 Ala wall same time gin Lys wall gin gin Leu Ser Tyr Gly G1 y Gly Ile Asp 530 535 540 Leu Leu Leu Asp Phe Ile Thr Thr Tyr Ser same time Lys A :: n Ser for Thr 545 550 555 560 Gly Ile gin Thr Lys Arg same time Phe Ser Ser Ser Phe Gly Ile Phe Gly 565 570 575 Gly Leu Arg Gly Leu Tyr same time Ser Tyr Tyr wall Leu Λ. ·: Η Lys wall Lys 580 585 590 Gly Ser Gly same time Leu Asp wall Ala Thr Gly Leu same time Tyr Arg Tyr Lys 595 600 UJ'l His Ser Lys Tyr Ser wall Gly Ile Ser Ile for Leu Tie gin Arg Lys 610 615 620 Ala Ser wall wall Ser Ser Gly Gly Asp Tyr Thr same time .'i.-R Phe wall Phe 625 630 635 640 same time Glu Gly Ala Ser His Phe Lys wall Phe Phe same time Tyr Gly Trp wall 645 650 655 Phe

(2) INFORMATION 0 SEQ. NO. 119: (I) SEQUENCE CHARACTERISTICS: (A) LENGTH: 167 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: various: letters (B) LOCATION 1 ... 167 (Xi) SEQUENCE DESCRIPTION: SEQ. NO. 119: Met Lys Leu Val Ser Leu Clay Val Ala Leu wall Phe Cys Cys Phe Leu 1 5 10 15 Gly Ala Val Glu Leu For Gly Val Tyr gin Thr gin Glu Phe Leu Tyr 20 25 30 Met Lys Ser Ser Phe Val Glu Phe Phe Glu His same time Gly Lys Phe Tyr 35 40 45 Ala Tyr Gly White Ser Asp Val Asp Gly Ser Lys Ala Lys Lys Asp Lys 50 55 60 Leu same time Pro Asn Pro Lys Leu Arg same time Arg Ser Asp Lys Gly wall wall 65 70 75 80 Phe Leu Ser Asp Leu White Lys Val Gly Glu gin Ser Tyr Lys Gly Gly 85 90 95 Lys Ala Tyr Asn Phe. Tyr Asp Gly Lys Thr Tyr His wall Arg wall Thr 100 105 110 gin same time Ser Asn Gly Asp Leu Glu Phe Thr Ser Ser Tyr Asp Lys Trp 115 120 125 Gly Tyr Val Gly Lys Thr Trp Lys Arg Leu Ser Asp Glu Glu 130 135 140 Ile Lys Asn Leu Lys Phe same time Leu Asp Glu wall Leu Lys 145 150 155 160

Thr Leu Lys Asp Ser Pro Ie 165 (2) INFORMATION 0 SEQ. ¢.: 120:

199 (i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 294 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 ... 294 (xi) SEQUENCE DESCRIPTION: SEQ. NO. 120:

Met Ser same time gin Ala Ser His Leu Asp same time Phe Met same time Ala Lys same time 1 5 10 15 for Lys Ser Phe Phe Asp same time Lys Gly same time Thr Lys Phe Ile Ala Ile 20 25 30 Thr Ser Gly Lys Gly Gly wall Gly Lys Ser same time Ile Ser Ala same time Leu 35 40 45 Ala Tyr Ser Leu Tyr Lys Lys Gly Tyr Lys wall Gly wall Phe Asp Ala 50 55 60 Asp Ile Gly Leu Ala same time Leu Asp wall Ile Phe Gly wall Lys Thr His 65 70 75 80 Lys same time Ile Leu His Ala Leu Lys Gly Glu Ala Lys Leu gin Glu Ile 85 90 95 Ile Cys Glu Ile Glu for Gly Leu Cys Leu Ile for Gly Asp Ser Gly 100 105 110 Glu Glu Ile Leu Lys Tyr Ile Ser Gly Ala Glu Ala Leu Asp Arg Phe 115 120 125 wall Asp Glu Glu Gly wall Leu Ser Ser Leu Asp Tyr Ile wall Ile Asp 130 135 140 Thr Gly Ala Gly Ile Gly Ala Thr Thr gin Ala Phe Leu same time Ala Ser 145 150 155 160 Asp Cys wall wall Ile wall Thr Thr for Asp for Ser Ala Ile Thr Asp 165 170 175 Ala Tyr Ala Cys Ile Lys Ile same time Ser Lys same time Lys Asp Glu Leu Phe 180 185 190 Leu Ile Ala same time Met wall Ala gin for Lys Glu Gly Arg Ala Thr Tyr • 195 200 205 Glu Arg Leu Phe Lys wall Ala Lys same time same time Ile Ala Ser Leu Glu Leu 210 215 220 His Tyr Leu Gly Ala Ile Glu same time Ser Ser Leu Leu Lys Arg Tyr wall 225 230 235 240 Arg Glu Arg Lys Ile Leu Arg Lys Ile Ala for same time Asp Leu Phe Ser 245 250 255 gin Ser Ile Asp gin Ile Ala Ser Leu Leu wall Ser Lys Leu Glu Thr 260 265 270 Gly Thr Leu Glu Ile for Lys Glu Gly Leu Lys Ser Phe Phe Lys Arg 275 280 285 Leu Leu Lys Tyr Leu Gly

290 (2) INFORMATION ABOUT SEQ. NO. 121:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 372 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULA TYPE: protein

200 (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) NAME / KEY: various characters (B) LOCATION 1 ... 372 (xi) SEQUENCE DESCRIPTION: SEQ. NO. 121:

Leu Glu for Ser Arg same time Arg Leu Lys His Ala Ala I'Iip Phe wall Gly 1 5 10 15 Leu Phe Ile wall Leu Phe Leu Ile Ile Met Lys His gin Thr Ser for 20 25 30 Tyr Ala Phe Thr His same time gin Ala Leu wall Thr gin Thr for for Tyr 35 40 I ', Phe Thr gin Leu Thr Ile for Lys for same time Asp Ala Leu Ser Ala His 50 55 60 Ala Ser Ser Leu Ile Ser Leu for same time Asp same time Leu Leu Ser Ala Tyr 65 70 75 80 Phe Ser Gly Thr Lys Glu Gly Ala Arg Asp wall Lys Ilfi Ser Ala same time 85 90 95 Leu Phe Asp Ser Lys Thr same time Arg Trp Ser Glu Ala Phe Ile Leu Leu 100 105 110 Thr Lys Glu Glu Leu Ser His His Ser His Glu Tyr Ile Lys Lys Leu 115 120 125 Gly same time for Leu Leu Phe Leu His Asp same time Lys Ile Leu Leu Phe wall 130 135 140 wall Gly wall Ser Met Gly Gly Trp Ala Thr Ser Lys Ile Tyr gin Phe 145 150 155 160 Glu Ser Ala Leu Glu for Ile His Phe Lys Phe Ala Arg Lys Leu Ser 165 170 175 Leu Ser for Phe Leu same time Leu Ser His Leu wall Arg same time Lys for Leu 180 185 190 same time Thr Thr Asp Gly Gly Phe Met Leu for Leu Tyr His Glu Leu Ala 195 200 205 Thr gin Tyr for Leu Leu Leu Lys Phe Asp gin gin same time same time for Arg 210 215 220 Glu Leu Leu Arg for same time Thr Leu same time His gin Leu gin for Ser Leu 225 230 235 240 Thr for Phe Lys Asp Cys Ala wall Met Ala Phe Arg same time His Ser Phe 245 250 255 Lys Asp Ser Leu Met Leu Glu Thr Cys Lys Thr for Thr Asp Trp gin 260 265 270 Lys for Ile Ser Thr same time Leu Lys same time Leu Asp Asp Ser Leu same time Leu 275 280 285 Leu same time Leu same time Gly Ile Leu Tyr Leu Ile His same time for Ser Asp Leu 290 295 300 Ser Leu Arg Arg Lys Glu Leu Trp Leu Ser Lys Leu Glu same time Ser same time 305 310 315 320 Ser Phe Lys Thr Leu Lys wall Leu Asp Lys Ala same time Glu wall Ser Tyr 325 330 335 for Ser Tyr Ser Leu same time for His Phe Ile Asp Ile wall Tyr Thr Tyr 340 345 350 same time Arg Ser His Ile Lys His Ile Arg Phe same time Met Ala Tyr Leu same time 355 360 365

Ser Leu Leu Lys 370 (2) SEQ ID NO. NO. 122:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 978 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear

201 (ii) MOLECULA TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori SIGN: (A) NAME / KEY: different characters (B) PLACEMENT 1 ... 978

(xi) SEQUENCE DESCRIPTION: SEQ. NO. 122:

Met Lys Lys Arg Lys His wall Ser Lys Lys wall Phe same time wall Ile Ile 1 5 10 15 Leu Phe wall Ala wall Phe Thr Leu Leu wall wall Ile His Lys Thr Leu 20 25 30 Ser same time Gly Ile His Ile gin same time Leu Lys Ile Gly Lys Leu Gly Ile 35 40 45 Ser Glu Leu Tyr Leu Lys Leu same time same time Lys Leu Ser Leu Glu wall Glu 50 55 60 Arg wall Asp Leu Ser Ser Phe Phe His gin Lys for Thr Lys Lys Arg 65 70 75 80 Leu Glu wall Ser Asp Leu Ile Lys same time Ile Arg Tyr Gly Ile Trp Ala 85 90 95 wall Ser Tyr Phe Glu Lys Leu Lys wall Lys Glu Ile Ile Leu Asp Asp 100 105 110 Lys same time Lys Ala same time Ile Phe Phe Asp Gly same time Lys Tyr Glu Leu Glu 115 120 125 Phe for Gly Ile Lys Gly Glu Phe Ser Leu Glu Asp Asp Lys same time Ile 130 135 140 Lys Leu Lys Ile Ile same time Leu Leu Phe Lys Asp wall Lys wall gin wall 145 150 155 160 Asp Gly same time Ala His Tyr Ser for Lys Ala Arg Lys Met Ala Phe same time 165 170 175 Leu Ile wall Lys for Leu wall Glu for Ser Ala Ala Ile Tyr Leu gin 180 185 190 Gly Leu Thr Asp Leu Lys Thr Ile Glu Leu Lys Ile same time Thr Ser for 195 200 205 Met Lys Ser Leu Ala Phe Leu Lys for Leu Phe gin Arg gin Ser gin 210 215 220 Lys same time Leu Lys Thr Trp Ile Phe Asp Lys Ile gin Phe Ala Ser Phe 225 230 235 240 Lys Ile Asp same time Ala Leu Ile Lys Ala same time Phe Thr for Ser Glu Phe 245 250 255 Ile for Ser Leu Leu Glu same time Ser wall wall Lys Ala Thr Leu Ile Lys 260 265 270 for Ser wall wall Phe same time Asp Gly Leu Ser for Ile Lys Met Asp Lys 275 280 285 Thr Glu Leu Ile Phe Lys same time Lys gin Leu Leu Ile gin for gin Lys 290 295 300 Ile Thr Tyr Glu Thr Met Glu Leu Thr Gly Ser Tyr Ala Thr Phe Ser 305 310 315 320 same time Leu Leu Glu Ala for Lys Leu Glu wall Phe Leu Lys Thr Thr for 325 330 335 same time Tyr Tyr Gly Asp Ser Ile Lys Asp Leu Leu Ser Ala Tyr Lys wall 340 345 350 wall Leu for Leu Asp Lys Ile Ser Met for Ser Ser Ala Asp Leu Lys 355 360 365 Leu Thr Leu gin Phe Leu Lys same time Thr Ala for Leu Phe Ser wall gin 370 375 380 Gly Ser wall same time Leu gin Glu Gly Thr Phe Ser Leu Tyr same time Ile for 385 390 395 400 Leu Tyr Thr gin Ser Ala gin Ile same time Leu Asp Ile Ala gin Glu Tyr 405 410 415

202

gin Tyr Ile Tyr Ile Asp Thr Ile His Thr Arg Tyr Ala same time Met Leu 420 425 430 Asp Leu Asp Ala Lys Ile Ala Leu Asp Leu Gly gin Lys same time Leu Ser 435 440 445 Leu Asp Ser Leu wall His Lys Ile gin wall A :: n Thr same time same time same time Ile 450 455 4 60 same time Met Arg Ser Tyr Asp for same time same time Thr gin Glu Asp for gin Thr 4 65 470 475 480 same time Phe Thr Leu Asp Leu Lys Ser Leu His Ser Ile Ile gin Glu Gly 485 490 495 Glu same time Ser Glu wall Phe Arg Arg Lys Ile Ile Asp Thr Ile Lys Ala 500 505 510 gin Ser Glu Asp Lys Phe Thr Lys Asp wall LLN; Tyr Ala Thr Gly Asp 515 520 525 Thr Leu Lys Ser Leu Ser Leu Ser Phe Asp PLII · Ser same time for Asp His 530 535 540 Ile gin Trp Ser wall for gin Leu Leu Leu Glu Gly Glu Phe Lys Asp 545 550 555 560 same time Ala Tyr Thr Phe Lys Ile Lys Asp Leu Lys Lys Ile Lys for Tyr 565 570 575 Ser for Ile Met Asp Tyr Ile Ala Leu Lys Asp Gly Ser Leu Glu wall 580 585 590 Ser Thr Ser Asp Phe wall same time Ile Asp Phe Phe Ala Lys Asp Leu Lys 595 600 605 Ile same time Leu for Ile Tyr Arg Ser Asp Gly ULT His Phe Asp Ser Phe 610 615 620 Ser Leu Phe Gly Ser Ile same time Lys Asp Glu ILT: Ser wall Tyr Thr for 625 630 635 640 Ser Lys Ser Ile Ser Ile Lys wall Lys Gly Asp gin Lys Asp Ile Thr 645 650 655 Leu same time same time Ile Asp Leu Ser Ile Asp Asp Phe Leu Asp Ser Lys Met 660 665 670 for Ala Ile Ala Gly Leu Phe Ser Lys Glu Arg Lys Glu Lys for Ser 675 680 685 Ser Lys Glu Ile gin Asp Glu Asp wall Phe Ile Ser Ala Lys gin Arg 690 695 700 Tyr Glu Lys Ala His Lys Ile Ile for Ile Ser Thr Arg Ile His Ala 705 710 715 720 Lys Asp wall wall Leu Ile Tyr Lys Lys Met for Phe for Leu Glu same time 725 730 735 Leu Asp Ile wall Ala gin Asp Asp Arg wall Lys Ile Asp Gly same time Tyr 740 745 750 Lys same time Ala Met Ile Met Ala Asp Leu wall H j s Gly Ala Leu Tyr Leu 755 760 765 Lys Ala His same time Phe Ser Gly Asp Tyr Ile same time Thr Ile Leu gin Lys 770 775 780 Asp Phe wall Glu Gly Gly Leu Phe Thr Leu Ile Gly Ala Leu Glu Asp 785 790 7'15 800 gin wall Phe same time Gly Glu Leu Lys Phe gin same time Thr Ser Leu Lys same time 805 810 815 Phe Ala Leu Met gin same time Met wall same time Leu Ile same time Thr Ile for Ser 820 825 830 Leu Ile wall Phe Arg same time for His Leu Gly Ala same time Gly Tyr gin Ile 835 840 845 Lys Thr Gly Ser wall wall Phe Gly Ile Thr Lys Glu Tyr Leu Gly Leu 850 855 860 Glu Lys Ile Asp Leu wall Gly Lys Thr Leu Asp Ile Ala Gly same time Gly 865 870 875 880 Ile Ile Glu Leu Asp Lys same time Lys Leu Asp Leu same time Leu Glu wall Ser 885 890 895 Thr Ile Lys Ala Leu Ser same time wall Leu same time Lys Ile for Ile wall Gly 900 905 910 Tyr Leu wall Leu Gly Lys Gly Gly Lys Ile Thr Thr same time wall same time wall 915 920 925 Lys Gly Thr Leu Asp Lys for Lys Thr gin V.il Thr Leu Ala Ser Asp 930 935 940

203

Ile Ile gin Ala for Phe Lys Ile Leu Arg Arg ile Phe Thr for Ile 945 950 955 960 Asp Ile Ile wall Asp Glu wall Lys Lys same time Asp Ser Lys Arg Lys 965 970 975

Leu Lys (2) SEQ ID NO. NO. 123:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 477 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii, MOLECULA TYPE: protein (iii, HYPOTHETICAL: YES (vi) ORIGINAL SOURCE:

(A, ORGANISM: Helicobacter pylori SIGN: (A) NAME / KEY: different characters (B, PLACEMENT 1 ... 477

(xi, SEQUENCE DESCRIPTION: SEQ ID NO: 123:

Met same time Thr Ile Ile Arg Tyr Ala Ser Leu Trp Gly Leu Cys Ile Thr 1 5 10 15 Leu Thr Leu Ala gin Thr for Ser Lys Thr for Asp Glu Ile Lys gin 20 25 30 Ile Leu same time same time Tyr Ser His Lys same time Leu Lys Leu Ile Asp for for 35 40 45 Thr Ser Ser Leu Glu Ala Thr for Gly Phe Leu for Ser for Lys Glu 50 55 60 Thr Ala Thr Thr Ile same time gin Glu Ile Ala Lys Tyr His Glu Lys Ser 65 70 75 80 Asp Lys Ala Ala Leu Gly Leu Tyr Glu Leu Leu Lys Gly Ala Thr Thr 85 90 95 same time Leu Ser Leu gin Ala gin Glu Leu Ser wall Lys gin Ala Met Lys 100 105 110 same time His Thr Ile Ala Lys Ala Met Phe Leu for Thr Leu same time Ala Ser 115 120 125 Tyr same time Phe Lys same time Glu Ala Arg Asp Thr for Glu Tyr Lys His Tyr 130 135 140 same time Thr gin gin Leu gin Ala gin wall Thr Leu same time wall Phe same time Gly 145 150 155 160 Phe Ser same time wall same time same time wall Lys Glu Lys Ser Ala Thr Tyr Arg Ser 165 170 175 Thr wall Ala same time Leu Glu Tyr Ser Arg gin Ser wall Tyr Leu gin wall 180 185 190 wall gin gin Tyr Tyr Glu Tyr Phe same time same time Leu Ala Arg Met Ile Ala 195 200 205 Leu gin Lys Lys Leu Glu gin Ile gin Thr Asp Ile Lys Arg wall Thr 210 215 220 Lys Leu Tyr Asp Lys Gly Leu Thr Thr Ile Asp Asp Leu gin Ser Leu 225 230 235 240 Lys Ala gin Gly same time Leu Ser Glu Tyr Asp Ile Leu Asp Met gin Phe 245 250 255 Ala Leu Glu gin same time Arg Leu Thr Leu Glu Tyr Leu Thr same time Leu Ser 260 265 270 wall Lys same time Leu Lys Lys Thr Thr Ile Asp Ala for same time Leu gin Leu 275 280 285 Arg Glu Arg gin Asp Leu wall Ser Leu Arg Glu gin Ile Ser Ala Leu 290 295 300 Arg Tyr gin same time Lys gin Leu same time Tyr Tyr for Lys Ile Asp wall Phe

204

305 310 315 320 Asp Ser Trp Leu Phe Trp Ile gin Lys for Ala Tyr Ala Thr Gly Arg 325 330 335 Phe Gly same time Phe Tyr for Gly gin gin same time Thr Ala Gly wall Thr Ala 340 345 350 Thr Leu same time Ile Phe Asp Asp Ile Gly Leu Are you Leu gin Lys gin Ser 355 360 365 Ile Met Leu Gly gin Leu Ala same time Glu Lys A :: n Leu Ala Tyr Lys Lys 370 375 380 Leu Glu gin Glu Lys Asp Glu gin Leu Tyr Fι f | Lys Ser Leu Asp Ile 385 390 p, r. 400 Ala Arg Ala Lys Ile Glu Ser Ser Lys Ala íit r Leu Asp Ala Ala same time 405 410 415 Leu Ser Phe Ala same time Ile Lys Arg Lys Tyr Ala same time Leu wall Asp 420 425 430 Phe Thr Thr Tyr Leu Arg Gly Leu Thr Thr Λι q Phe Asp Ala Glu wall 435 440 445 Ala Tyr same time Leu Ala Leu same time same time Tyr Glu V.l gin Lys Ala same time Tyr 450 455 4 60 Ile Phe same time Ser Gly His Lys ill Asp Asp Ty vai His

465 470 -175 (2) INFORMATION ABOUT SEQ. NO. 124:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 412 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear

(Ii) MOLECULA TYPE: protein (Iii) HYPOTHETICAL: YES (Vi) ORIGINAL SOURCE: (A) Organ: [Grunts] Helic □ bac Ľer pyloj ri (Ix) SIGN: (A) NAME / KEY : Differently : letters (B) located: 1Ε 1, .. .4: 12 (Xi) SEQUENCE DESCRIPTION: SEQ. no. :: L24: Met Leu Ser Phe Ile Ser Ala Phe Asp Lys Arq Gly wall Ser Ile Arg 1 5 10 15 Leu Leu Thr Ala Leu Leu Leu Leu Phe Ser Leu Gly Leu Ala Lys Asp 20 25 30 Leu Glu Ile gin Thr Phe wall Ala Lys Tyr Leu Ser Lys same time gin Lys 35 40 45 Ile gin Ala Leu gin Glu gin Ile Asp Ala Leu Asp Ser gin Glu Lys 50 55 60 wall wall Ser Lys Trp Asp same time for Ile Leu Tyr Leu Gly Tyr same time same time 65 70 75 80 Ala same time wall Ser Asp Phe Phe Arg Leu Asp Ser Thr Leu Met gin same time 85 90 95 Met Ser Leu Gly Leu Ser gin Lys wall Asp Leu same time Gly Lys Lys Leu 100 105 110 Thr gin Ser Lys Met Ile same time Leu Glu Lys gin Lys Lys Ile Leu Glu 115 120 125 Leu Lys Lys Thr Lys gin gin Leu wall Ile same time Leu Met Ile same time Gly 130 135 140 Ile Glu same time Tyr Lys same time gin gin Glu Ile Glu Leu Leu same time Thr Ala 145 150 155 160 Ile Lys same time Leu Glu same time Thr Leu Tyr gin Ala same time His Ser Ser Ser 165 170 175 for Asp Leu Ile Ala Ile Ala Lys Leu Glu 1 le Leu Lys Ser Leu Leu

180 185 190

205

Glu Ile gin Lys same time Asp Leu Glu wall Ala Leu Ser Ser Ser His Tyr 195 200 205 Ser Met Gly Glu Leu Thr Phe Lys Glu same time Glu Ile Leu Ser Ile Ala 210 215 220 for Lys same time Phe Glu Phe same time same time Glu gin Glu Leu His same time Ile Ser 225 230 235 240 Ala Thr same time Tyr Asp Ile Ala Ile Ala Arg Leu Asp Glu Glu Lys Ala 245 250 255 gin Lys Asp Ile Thr Leu Ala Lys Lys Ser Phe Leu Glu Asp Ile same time 260 265 270 wall Thr Gly wall Tyr Tyr Phe Arg Ser Lys gin Tyr Tyr same time Tyr Asp 275 280 285 Met Phe Ser wall Ala Leu Ser Ile for Leu for Leu Tyr Gly Lys gin 290 295 300 Ala Lys Leu wall Glu gin Lys Lys Lys Glu Ser Leu Ala Phe Lys Ser 305 310 315 320 Glu wall Glu same time Ala Lys same time Lys Thr Arg His Leu Ala Leu Lys Leu 325 330 335 Leu Lys Lys Leu Glu Thr Leu gin Lys same time Leu Glu Ser Ile same time Lys 340 345 350 Ile Ile Lys gin same time Glu Lys Ile Ala gin Ile Tyr Ala Leu Asp Leu 355 360 365 Lys Thr same time Gly Asp Tyr same time Ala Tyr Tyr same time Ala Leu same time Asp Lys 370 375 380 Ile Thr Ile gin Ile Thr gin Leu Glu Thr Leu Ser Ala Leu same time Ser 385 390 395 400 Ala Tyr Leu Ser Leu gin same time Leu Lys Gly Leu Glu

405 410 (2, SEQ ID NO: 125:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 137 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: various characters (B, LOCATION 1 ... 137 (xi) SEQUENCE DESCRIPTION: SEQ. NO. 125: Met 1 Arg ile Val Arg Asn Leu Phe Leu Val Ser Phe Val Ala Tyr Ser 5 10 15 Ser Ala Phe Ala Asp Leu Glu Thr Gly Thr Lys Asn Asp Lys Lys 20 25 30 Ser Gly Lys Lys Phe Tyr Lys Asu His Gly Ser Glu Thr 35 40 45 Glu Thr Lys Asn Thr Lys Lys Leu Tyr Thr Lys Asn Ser Gly 50 55 60 Leu 65 Glu Gly Val Asp Leu Glu Lys Ser For Asn Leu Lys Ser His Lys 70 75 80 Lys Ser Asp Lys Lys Phe Tyr Lys Gin Leu Ala Lys Asn Asn As Ala 85 90 95 Glu Gly Val Ser Met For Val Val Asn Phe Asn Lys Ala Leu Ser Phe 100 105 110 Gly Gly Pro Tyr Phe Glu Thr Lys Ser Lys Lys Thr Gin Tyr Met Asp 115 120 125 Gly Leu Met Met His White Arg Phe

206

130 135 (2) INFORMATION ABOUT SEQ. NO. 126:

(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)

(A) NAME / KEY: various characters (B) LOCATION 1 ... 309 (xi, SEQUENCE DESCRIPTION: SEQ ID NO: 126:

Leu Met for gin same time gin Leu wall Ile Thr Ile Ile Asp Glu Ser Gly 1 5 10 15 Ser Lys gin Leu Lys Phe Ser Lys same time Leu Lys Arg same time Leu Ile Ile 20 25 30 Ser wall wall Ile Leu Leu Leu Ile wall Gly Leu Gly wall Gly Phe Leu 35 40 45 Lys Phe Leu Ile Ala Lys Met Asp Thr Met Thr Ser Glu Arg same time Ala 50 55 60 wall Leu Arg Asp Phe Arg Gly Leu Tyr gin Lys same time Tyr Ala Leu Ala 65 70 75 80 Lys Glu Ile Lys same time Lys Arg Glu Glu Leu Phe Ile wall Gly gin Lys 85 90 95 Ile Arg Gly Leu Glu Ser Leu Ile Glu Ile Lys Lys Gly Ala same time Gly 100 105 110 Gly dy His Leu Tyr Asp Glu wall Asp Leu Glu same time Leu Ser Leu same time 115 120 125 gin Lys His Leu Ala Leu Met Leu Ile for same time Gly Met for Leu Lys 130 135 140 Thr Tyr Ser Ala Ile Lys for Thr Lys Glu Arg same time His for Ile Lys 145 150 155 160 Lys Ile Lys Gly wall Glu Ser Gly Ile Asp Phe Ile Ala for Leu same time 165 170 175 Thr for wall Tyr Ala Ser Ala Asp Gly Ile wall Asp Phe wall Lys Thr 180 185 190 Arg Ser same time Ala Gly Tyr Gly same time Leu wall Arg Ile Glu His Ala Phe 195 200 205 Gly Phe Ser Ser Ile Tyr Thr His Leu Asp His wall same time wall gin for 210 215 220 Lys Ser Phe Ile gin Lys Gly gin Leu Ile Gly Tyr Ser Gly Lys Ser 225 230 235 240 Gly same time Ser Gly Gly Glu Lys Leu His Tyr Glu wall Arg Phe Leu Gly 245 250 255 Lys Ile Leu Asp Ala Glu Lys Phe Leu Ala Trp Asp Leu Asp His Phe 260 265 270 gin Ser Ala Leu Glu Glu same time Lys Phe Ile Glu Trp Lys same time Leu Phe 275 280 285 Trp wall Leu Glu Asp Ile wall gin Leu gin Glu His wall Asp Lys Asp 290 295 300 Thr Leu Lys Gly gin 305 (2) SEQ ID NO. No. d. : 127:

(i) SEQUENCE CHARACTERISTICS:

207 (A) LENGTH: 332 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 ... 332

(xi) SEQUENCE DESCRIPTION: SEQ. NO. 127:

wall Leu Tyr Phe Leu Thr Ser Leu Phe Ile Cys Ser Leu Ile wall Leu 1 5 10 15 Trp Ser Lys Lys Ser Met Leu Phe wall Asp same time Ala same time Lys Ile gin 20 25 30 Gly Phe His His Ala Arg Thr for Arg Ala Gly Gly Leu Gly Ile Phe 35 40 45 Leu Ser Phe Ala Leu Ala Cys Tyr Leu Glu for Phe Glu Met for Phe 50 55 60 Lys Gly for Phe wall Phe Leu Gly Leu Ser Leu wall Phe Leu Ser Gly 65 70 75 80 Phe Leu Glu Asp Ile same time Leu Ser Leu Ser for Lys Ile Arg Leu Ile 85 90 95 Leu gin Ala wall Gly wall wall Cys Ile Ile Ser Ser Thr for Leu wall 100 105 110 wall Ser Asp Phe Ser for Leu Phe Ser Leu for Tyr Phe Ile Ala Phe 115 120 125 Leu Phe Ala Ile Phe Met Leu wall Gly Ile Ser same time Ala Ile same time Ile 130 135 140 Ile Asp Gly Phe same time Gly Leu Ala Ser Gly Ile Cys Ala Ile Ala Leu 145 150 155 160 Leu wall Ile His Tyr Ile Asp for Ser Ser Leu Ser Cys Leu Leu Ala 165 170 175 Tyr Met wall Leu Gly Phe Met wall Leu same time Phe for Ser Gly Lys Ile 180 185 190 Phe Leu Gly Asp Gly Gly Ala Tyr Phe Leu Gly Leu wall Cys Gly Ile 195 200 205 Ser Leu Leu His Leu Ser Leu Glu gin Lys Ile Ser wall Phe Phe Gly 210 215 220 Leu same time Leu Met Leu Tyr for wall Ile Glu wall Leu Phe Ser Ile Leu 225 230 235 240 Arg Arg Lys Ile Lys Arg gin Lys Ala Thr Met for Asp same time Leu His 245 250 255 Leu His Thr Leu Leu Phe Lys Phe Leu gin gin Arg Ser Phe same time Tyr 260 265 270 for same time for Leu Cys Ala Phe Ile Leu Ile Leu Cys same time Leu for Phe 275 280 285 Ile Leu Ile Ser wall Leu Phe Arg Leu Asp Ala Tyr Ala Leu Ile wall 290 295 300 Ile Ser Leu wall Phe Ile Ala Cys Tyr Leu Ile Gly Tyr Ala Tyr Leu 305 310 315 320 same time Arg gin wall Cys Ala Leu Glu Lys Arg Ala Phe 325 330

(2) INFORMATION ABOUT SEQ. NO. 128:

(i) SEQUENCE CHARACTERISTICS:

(A, LENGTH: 271 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear

208 (ii) MOLECULA TYPE: protein (iii, HYPOTHETICAL: YES (vi, ORIGINAL SOURCE:

(A, ORGANISM: Helicobacter pylori (ix)

(A) NAME / KEY: various characters (B) LOCATION 1 ... 271 (xi, SEQUENCE DESCRIPTION: SEQ ID NO: 128:

Met same time Ile Phe Lys Arg Ile Ile Cys wall Thr Ala I le wall Leu Gly 1 5 10 15 Phe Phe same time Leu Leu Asp Ala Lys His His Lys Glu I.ys Lys Glu Asp 20 25 30 His Lys Ile Thr Arg Glu Leu Lys wall Gly Ala same time LRO wall for His 35 40 * 4. Ala gin Ile Leu gin Ser wall wall Asp Asp Leu Lys G1 u Lys Gly Ile 50 55 60 Lys Leu wall Ile wall Ser Phe Thr Asp Tyr wall Leu Γιο same time Leu Ala 65 70 75 80 Leu same time Asp Gly Ser Leu Asp Ala same time Tyr Phe gin His Arg for Tyr 85 90 95 Leu Asp Arg Phe same time Leu Asp Arg Lys Met His Leu wall Gly Leu Ala 100 105 110 same time Ile His wall Glu for Leu Arg Phe Tyr Ser gin I.ys Ile Thr Asp 115 120 125 Ile Lys same time Leu Lys Lys Gly Ser wall Ile Ala wall for same time Asp for 130 135 140 Ala same time gin Gly Arg Ala Leu Ile Leu Leu His Lys gin Gly Leu Ile 145 150 155 160 Ala Leu Lys Asp for Ser same time Leu Tyr Ala Thr Glu Phe Asp Ile wall 165 170 175 Lys same time for Tyr same time Ile Lys Ile Lys for Leu Glu Ala Ala Leu Leu 180 185 190 for Lys wall Leu Gly Asp wall Asp Gly Ala Ile Ile Thr Gly same time Tyr 195 200 205 Ala Leu gin Ala Lys Leu Thr Gly Ala Leu Phe Ser Glu Asp Lys Asp 210 215 220 Ser for Tyr Ala same time Leu wall Ala Ser Arg Glu Asp same time Ala gin Asp 225 230 235 240 Glu Ala Ile Lys Ala Leu Ile Glu Ala Leu gin Ser 6LU Lys Thr Arg 245 250 255 Lys Phe Ile Leu Asp Thr Tyr Lys Gly Ala Ile Ile for Ala Phe 260 265 270

(2, SEQ ID NO: 129:

(i, SEQUENCE CHARACTERISTICS:

(A, LENGTH: 316 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: various characters (B, LOCATION 1 ... 316)

209 (xi) SEQUENCE DESCRIPTION: SEQ. NO. 129:

Met gin Glu Phe Ser Leu Trp Cys Asp Phe Ile Glu Arg Asp Phe Leu 1 5 10 15 Glu same time Asp Phe Leu Lys Leu Ile same time Lys Gly Ala Ile Cys Gly Ala 20 25 30 Thr Ser same time for Ser Leu Phe Cys Glu Ala Ile Thr Lys Ser Ala Phe 35 40 45 Tyr gin Asp Glu Ile Ala Lys Leu Lys Gly Lys Lys Ala Lys Glu Ile 50 55 60 Tyr Glu Thr Leu Ala Leu Lys Asp Ile Leu gin Ala Ser Ser Ala Leu 65 70 75 80 Met for Leu Tyr Glu Lys Asp for same time same time Gly Tyr Ile Ser Leu Glu 85 90 95 Ile Asp for Phe Leu Glu Asp Asp Ala Ile Lys Ser Ile Asp Glu Ala 100 105 110 Lys Arg Leu Phe Lys Thr Leu same time Arg for same time wall Met Ile Lys wall 115 120 125 for Ala Ser Glu Ser Ala Phe Glu wall Ile Ser Ala Leu Ala gin Ala 130 135 140 Ser Ile for Ile same time wall Thr Leu wall Phe Ser for Lys Ile Ala Gly 145 150 155 160 Glu Ile Ala gin Ile Leu Ala Lys Glu Ala Arg Lys Arg Ala wall Ile 165 170 175 Ser wall Phe wall Ser Arg Phe Asp Lys Glu Ile Asp for Leu wall for 180 185 190 gin same time Leu gin Ala gin Ser Gly Ile Met same time Ala Thr Glu Cys Tyr 195 200 205 Tyr gin Ile same time gin His Ala same time Lys Leu Ile Ser Thr Leu Phe Ala 210 215 220 Ser Thr Gly wall Lys Ser same time Ser Leu Ala Lys Asp Tyr Tyr Ile Lys 225 230 235 240 Ala Leu Cys Phe Lys same time Ser Ile same time Thr Ala for Leu Asp Ala Leu 245 250 255 same time Ala Tyr Leu Leu Asp for same time Thr Glu Cys gin Thr for Leu Lys 260 265 270 Ile Thr Glu Ile Glu Ala Phe Lys Lys Glu Leu Lys Thr His same time Ile 275 280 285 Asp Leu Glu same time Thr Ala gin Lys Leu Leu Lys Glu Gly Leu Ile Ala 290 295 300 Phe Lys gin Ser Phe Glu Lys Leu Leu Ser Ser Phe

305 310 315 (2) INFORMATION ABOUT SEQ. NO. 130:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 260 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULA TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(Ä) NAME / KEY: various characters (B) LOCATION 1 ... 260 (xi) SEQUENCE DESCRIPTION: SEQ. NO. 130:

Met Lys Thr Asn Gly His Phe Lys Lys Asp Phe Ala Trp Lys Lys Cys Phe 15 10 15

210

Leu Val Gly Ala Val Val Leu Val Gly Cys Ser Pro His Ile 20 25 30 Ile Glu Thr same time Glu wall Ala Leu Lys Leu Λ :: ιι Tyr His for Ala Ser 35 40 45 Glu Lys wall gin Ala Leu Asp Glu Lys Ile I. ï-II Leu Leu Arg for Ala 50 55 60 Phe gin Tyr Ser Asp same time Ile Ala Lys Glu You. Glu same time Lys Phe Lys 65 70 /?> 80 same time gin Thr Thr Leu Lys wall Glu Glu Ile Leu gin same time gin Gly Tyr 85 90 95 Lys wall Ile same time wall Asp Ser Ser Asp Lys :: Λ ρ Asp Phe Ser Phe Ala 100 105 110 gin Lys Lys Glu Gly Tyr Leu Ala wall Ala mol same time Gly Glu Ile wall 115 120 125 Leu Arg for Asp for Lys Arg Thr Ile gin I.y :: Lys Ser Glu for Gly 130 135 140 Leu Leu Phe Ser Thr Gly Leu Asp Lys Met G 1 n Arg wall Leu Ile for 145 150 I '.'. 160 Ala Gly Phe wall Lys wall Thr Ile Leu Glu I '. n Met Ser Gly Glu Ser 165 170 175 Leu Asp Ser Phe Thr Met Asp Leu Ser Glu lii-in Asp Ile gin Glu Lys 180 185 190 Phe Leu Lys Thr Thr His Ser Ser His Ser G1 y Gly Leu wall Ser Thr 195 200 205 Met wall Lys Gly Thr Asp same time Ser same time Asp ΛΙ.ι Ile Lys Ser Ala Leu 210 215 220 same time Lys Ile Phe Ala Ser Ile Met gin Glu mol Asp Lys Lys Leu Thr 225 230 235 240 gin Arg same time Leu Glu Ser Tyr gin Lys Asp Alu Lys Glu Leu Lys same time 245 250 255 Lys Arg same time Arg 260

(2) INFORMATION ABOUT SEQ. NO. 131:

(1) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 1382 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 ... 1382

(xi) SEQUENCE DESCRIPTION: SEQ. NO. 131:

Leu same time Phe same time same time Leu Thr Ala same time Gly Ala Leu same time Phe same time Gly 1 5 10 15 Tyr Ala for Ser Leu Thr Lys Ala Leu Met same time wall Ser Gly gin Phe 20 25 30 wall Leu Gly same time same time Gly Asp Ile same time Leu Ser Asp Ile same time Ile Phe 35 40 45 Asp same time Ile Thr Lys Ser wall Thr Tyr same time Ile Leu same time Ala gin Lys 50 55 60 Gly Ile Thr Gly Ile Ser Gly Ala same time Gly Tyr Glu Lys Ile Leu Phe 65 70 75 80 Tyr Gly Met Lys Ile gin same time Ala Thr Tyr Ser Asp same time same time same time Ile 85 90 95 gin Thr Trp Ser Phe Ile same time for Leu same time So r Ser gin Ile Ile gin

211

100 105 110 Glu Ser Ile Lys same time Gly Asp Leu Thr Ile Glu wall Leu same time same time for 115 120 125 same time Ser Ala Ser same time Thr Ile Phe same time Ile Ala for Glu Leu Tyr same time 130 135 140 Tyr gin Asp Ser Lys gin same time for Thr Gly Tyr Ser Tyr Asp Tyr Ser 145 150 155 160 Asp same time gin Ala Gly Thr Tyr Tyr Leu Thr Ser same time Ile Lys Gly Leu 165 170 175 Phe Thr for Lys Gly Ser gin Thr for gin Thr for Gly Thr Tyr Ser 180 185 190 for Phe same time gin for Leu same time Ser Leu same time Ile Tyr same time Lys Gly Phe 195 200 205 Ser Ser Glu same time Leu Lys Thr Leu Leu Gly Ile Leu Ser gin same time Ser 210 215 220 Ala Thr Leu Lys Glu Met Ile Glu Ser same time gin Leu Asp same time Ile Thr 225 230 235 240 same time Ile same time Glu wall Leu gin Leu Leu Asp Lys Ile Lys Ile Thr gin 245 250 255 Ala gin Lys gin Ala Leu Leu Glu Thr Ile same time His Leu Thr Asp same time 260 265 270 Ile same time gin Thr Phe same time same time Gly same time Leu wall Ile Gly Ala Thr gin 275 280 285 Asp same time wall Thr same time Ser Thr Ser Ser Ile Trp Phe Gly Gly same time Gly 290 295 300 Tyr Ser Ser for Cys Ala Leu Asp Ser Ala Thr Cys Ser Ser Phe Arg 305 310 315 320 same time Thr Tyr Leu Gly gin Leu Leu Gly Ser Thr Ser for Tyr Leu Gly 325 330 335 Tyr Ile same time Ala Asp Phe Lys Ala Lys Ser Ile Tyr Ile Thr Gly Thr 340 345 350 Ile Gly Ser Ser same time Ala Phe Glu Ser Gly Gly Ser Ala Asp wall Thr 355 360 365 Phe gin Ser Ala same time same time Leu wall Leu same time Lys Ala same time Ile Glu Ala 370 375 380 gin Ala Thr Asp same time Ile Phe same time Leu Leu Gly gin Glu Gly Ile Asp 385 390 395 400 Lys Ile Phe same time gin Gly same time Leu Ala same time wall Leu Ser gin Met Ala 405 410 415 Met Glu Lys Ile Lys gin Ala Gly Gly Leu Gly same time Phe Ile Glu same time 420 425 430 Ala Leu Ser for Leu Ser Lys Glu Leu for Ala Ser Leu gin Asp Glu 435 440 445 Thr Leu Gly gin Leu Ile Gly gin same time same time Leu Asp Asp Leu Leu same time 450 455 4 60 same time Ser Gly wall Met same time Glu Ile gin same time Ile Ile Ser gin Lys Leu 465 470 475 480 Ser Ile Phe Gly same time Phe wall Thr for Ser Ile Ile Glu same time Tyr Leu 485 4 90 495 Ala Lys gin Ser Leu Lys Ser Met Leu Asp Asp Lys Gly Leu Leu same time 500 505 510 Phe Ile Gly Gly Tyr Ile Asp Ala Ser Glu Leu Ser Ser Ile Leu Gly 515 520 525 wall Ile Leu Lys Asp Ile Thr same time for for Thr Ser Leu gin Lys Asp 530 535 540 Ile Gly wall wall Ala same time Asp Leu Leu same time Glu Phe Leu Gly gin Asp 545 550 555 560 wall wall Lys Lys Leu Glu Ser gin Gly Leu wall Ser same time Ile Ile same time 565 570 575 same time wall Ile Ser gin Gly Gly Leu Ser Gly wall Tyr same time gin Gly Leu 580 585 590 Gly Ser wall Leu for for Ser Leu gin same time Ala Leu Lys Glu same time Asp 595 600 605 Leu Gly Thr Leu Leu Ser for Arg Gly Leu His Asp Phe Trp gin Lys 610 615 620 Gly Tyr Phe same time Phe Leu Ser same time Gly Tyr wall Phe wall same time same time Ser

212

625 630 635 640 Ser Phe Ser Asn Ala Thr Gly Gly Ser 645 Leu Asn Phe V.il Ala Asn 650 655 Lys Ser Phe Asn Gly Asp Asn Thr 660 665 Asp Phe Gi-r Lys Tyr 670 gin Gly Ala Leu White Phe Ala Ser Asn Gly 675 680 Val Ser Asn 11 «. · Asn Ι.Η5 Thr Thr Leu Asn Ala Thr Asn Gly Leu Ser Leu Asn Ala Gly Leu Asn 700 same time wall 705 Ser Val Gin Lys Gly Glu White Cys 710 Asn Leu Al.i Asn Cys 715 for 720 Thr Thr Lys Asn Ser Ser Pro Al Asn 725 Ser Ser Thr Pro Thr 730 735 same time Glu Ser Leu Ser Val His Ala Asn Asn 740 745 Phe Thr Phe I, -ii Gly Thr 750 Ile Ile Ser Asn Gly Ala White Asp Leu Ser 755 760 Gin Val Thr Asn Asn Ser wall Ile Gly Thr Leu Asn Leu Asn Glu Asn 770 775 Ala Thr Leu in Ala Asn 780 same time Leu 785 Thr White Thr Asn Ala Phe Asn Asn 790 Ala Ser Asn Ser Thr Ala same time 800 Ile Asp Gly Asn Phe Thr Leu Asn Gin 806 Gin Ala Thr I, ru Ser Thr 810 815 same time Ala Ser Gly Leu As Met Val Gly Asn 820 825 Phe Asn Ser Tyr Gly Asp 830 Leu wall Phe Asn Leu Ser His Ser Val Ser 835 840 His Ala Il Iln Asn Thr 845 gin Gly Thr Ala Thr White Met Ala Asn Asn 850 855 Asn Pro Leu IJe Gin Phe 860 same time Ala 865 Ser Lys Glu Val Gly Thr Tyr 870 Thr Leu White Asp Ser Ala 875 Lys 880 Ala Tyr Tyr Gly Tyr Asn Asn Gin 885 Thr Gly Gly Ser Ser 890 895 Leu Asp Asn Tyr Leu Lys Leu Tyr Ala Leu 900 905 Asp Aspens Asn Gly Lys 910 His Met Val Thr Asp Asn Gly Leu Thr 915 920 Tyr Asn Gly Gin Al Val 925 Ser wall Lys Asp Gly Gly Le Val Val Gly 930 935 Phe Lys Asp Ser Gin Asn 941 gin Tyr 945 White Tyr Thr Ser White Leu Tyr Asn 950 Lys Val Lys Il Ala Val 955 Ser 960 same time Asp Pro Goals Asn Asn Pro Gin Ala 965 For Thr Leu Lys Gin Tyr 970,975 Ile Ala Gin Gly Gly Val Gin Ser Val 980 985 Asp Ser J Asp Gin Ala 990 Gly Gly Asn Gin Ala White Asn Trp Leu Asn 995 1000 Lys White Phe Glu Thr Lys 1005 Gly Ser For Leu Phe Ala For Tyr Tyr Leu 1010 1015 Glu Ser His Ser Thr Lys 1020 Asp Leu Thr Thr Ala Ala Gly Asp Ala 1025 1030 Asn Thr Leu Glu Val ile 1035 Ala 1040 same time For Asn Phe Lys Asn Asp Ala Thr 1045 Asn Leu Gin Asn Thr 1050 1055 Tyr Thr Gin Gin Met Ser Thr Ser 1060 1065 1070 Thr Phe Ala Arg Ser Phe Leu Glu Arg 1075 1080 Leu Glu Ala Lys Asn 1085 Lys Arg Phe Ala Asp Ala White For Asn Ala 1090 1095 Met Asp Val ile Leu Lys 1100 Tyr Ser Gin Arg Asn Arg Lys Asn 1105 1110 Val Trp Ala Thr Gly Val Gly 1120 Gly Ala Ser Phe White Ser Gly Gly Thr 1125 Gly Thr Leu Tyr Gly Clay Asn 1130 1135 wall Gly Tyr Asp Arg Phe White Lys Gly Val White Val Gly Gly Tyr Ala 1140 1145 1150 Ala Tyr Gly Tyr Ser Gly Asn Thr Gin Ser Gly Ser

213

1155 1160 1165

Ser Asn Val Asn Val Gly Val Ser Tyr Ala Ala Phe I Lys Arg Ser 1170 1175 1180 Glu Leu Thr Met Leu Asn Glu Thr Trp Gly Tyr Lys Thr Phe 1185 1190 1195 1200 Ile Asn Ser Tyr Asp For Leu Leu Ser io n Asn Gin Ser Tyr Arg 1205 1210 1215 Tyr Asp Thr Trp Thr Thr Asp Ala Lys White Asn Tyr Gly Tyr Asp Phe 1220 1225 1230 Met Phe Lys. Asp Lys Ser Val ile Phe Lys Gin Val Gly Leu Ser 1235 1240 1245 Tyr Tyr Tyr White Gly Leu Ser Gly Leu Arg Gly White Met Asp Asp Pro 1250 1255 1260 Ile Asr Gin Phe Arg Ala Asn Ala Asp Pro Asn Lys 1265 1270 1275 1280 Leu Thr ile Asn Phe Ala Leu Glu Ser Arg His Tyr Lys Asn 1285 1290 1295 Ser Tyr Tyr Phe Val Ala Asp Val Gly Arg Asp Leu Phe White Asn 1300 1305 1310 Ser Met Gly Asp Lys Met Val Arg Phe Gly Asn Asn Thr Leu Ser 1315 1320 1325 Tyr Arg Gly Gly Arg Tyr Asn Thr Phe Ala Ser ile ile Thr Gly 1330 1335 1340 Gly Glu White Arg Leu Phe Lys Thr Phe Tyr Val Asn Ala Gly White Gly 1345 1350 1355 1360 Ala Arg Phe Gly Leu Aspr Asly Thr Gly Asn

1365 1370

Gly Met Arg Tyr Ala Phe 1380 (2) SEQ. NO. 132:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 262 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 ... 262

(xi) SEQUENCE DESCRIPTION: SEQ. 0.:132:

Met Lys Lys Ile Gly Leu Ser Leu Cys Leu wall Leu Ser Leu Gly Phe 1 5 10 15 Leu Lys Ala His Glu wall Ser Ala Glu Glu Ile Ala Asp Ile Phe Tyr 20 25 30 Lys Leu same time Ala Lys Glu for Lys Met Lys Ile same time His Thr Lys Gly 35 40 45 Phe Cys Ala Lys Gly wall Phe Leu for same time for gin Ala Arg Glu Asp 50 55 60 Leu Glu wall for Leu Leu same time Glu Lys Glu Ile for Ala Ser wall Arg 65 70 75 80 Tyr Ser Leu Gly Gly wall Ala Met Asp Asp Lys Ser Lys wall Arg Gly 85 90 95 Met Ala Leu Lys Leu Glu same time gin same time Ala Ser Trp Thr Met wall Met 100 105 110 Leu same time Thr Glu Ile same time Phe Ala Lys same time for Glu Glu Phe Ala gin 115 120 125

214

Phe Phe Glu Met Arg Lys Asn Gly Lys Val Asp Glu Ala Arg 130 135 Ile Lys Lys Leu Tyr Glu Glu wall for Ser Tyr Arg same time Phe Ala Ala 145 150 155 160 Tyr Met Lys Thr Ile Gly Ile Ser Ser Ser wall Ala / \ N :: Thr for Tyr 165 170 175 Tyr Ser wall His Ala Phe Lys Phe Lys Asp Lys Lys C 1 u Lys Leu Leu 180 185 190 for Ala Arg Trp Lys Phe wall for Lys Glu Gly wall Lys Tyr Leu same time 195 200 205 for gin Glu Leu Lys gin Lys Asp Ser same time Tyr Leu I. ï · ιι Ser Ser Phe 210 215 220 gin gin His Leu Lys same time Lys for Ile Glu Tyr gin M.-L Tyr Leu wall 225 230 235 240 Phe Ala same time gin same time Asp Ala Thr same time Asp Thr Thr Al.i Leu Trp Lys 245 250 255 Gly Ser Ile Arg same time Tyr

260 (2) INFORMATION ABOUT SEQ. No .-. 133:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 246 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) LOCATION 1 ... 246 (Xi) SEQUENCE DESCRIPTION: SEQ. NO. 133: Met Lys Gin Phe Lys Lys Lys For Lys Lys White Lys Arg Ser His Gin 1 5 10 15 same time gin Lys Thr White Leu Lys Arg For Leu Trp Leu Met For Leu Leu 20 25 30 Ile Gly Gly Phe Ala Ser. Gly Val Tyr 34 40 45 Gly Leu Ser Trp Gly Glu Lys 50 55 60 Trp Tyr Ala Trile Ser Cys Asp Lys Trp Glu Glu Lys Thr Gin Gin 65 70 Phe Thr Gly Asn Gin Leu White Thr Lys Thr Trp Ala Gly Gly Asn Ala 85 Ala same time Tyr Tyr His Ser Gin Asn Asn Gin Asp Thr Ala Asn Leu 100 105 110 Lys same time Asp Gn Thr Tyr Phe Leu Ser Gn Ler Tyr Thr 115 120 125 Gly Gly Glu Tyr Asn Gly Gly Asn Leu Asp Glu Leu Gly Ser Asn 130 135 140 Ala Thr Phe Asn Leu Gly Ala Ser Ser Gly Asn Ser Phe Thr Ser Trp 145 150 155 160 Tyr for Asn Gly His Thr Asp Val Thr Phe Ser Ala Gly Thr White Asn 165 170 175 wall same time Asn Ser Val Glu 180 185 190 Thr His Thr Gly Thr Lys Val Thr 195 200 205 Ile same time Ser Asn White Ser Ala Tyr Lys Thr Ser Gin V.il Asn Val Gly

215

210 215 220

Asn Ala Asn Ser Val White Thr White Asn Ser Val Leu Asn Gly Glu 225 230 235 240

Tyr Leu Gin Phe Phe Ser

245 (2) INFORMATION ABOUT SEQ. NO. 134:

(1) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 245 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 ... 245

(xi, SEQUENCE DESCRIPTION: SEQ ID NO: 134:

Met Ile Lys Lys Thr Leu Ala Ser wall Leu Leu Gly Leu Ser Leu Met 1 5 10 15 Ser wall Leu same time Ala Lys Glu Cys wall Ser for Ile Thr Arg Ser wall 20 25 30 Lys Tyr His gin gin Ser Ala Glu Ile Arg Ala Leu gin Leu gin Ser 35 40 45 Tyr Lys Met Ala Lys Met Ala Leu Asp same time same time Leu Lys Leu wall Lys 50 55 60 Asp Lys Lys for Ala wall Ile Leu Asp Leu Asp Glu Thr wall Leu same time 65 70 75 80 Thr Phe Asp Tyr Ala Gly Tyr Leu val · Lys same time Cys Ile Lys Tyr Thr 85 90 95 for Glu Thr Trp Asp Lys Phe Glu Lys Glu Gly Ser Leu Thr Leu Ile 100 105 110 for Gly Ala Leu Asp Phe Leu Glu Tyr Ala same time Ser Lys Gly wall Lys 115 120 125 Ile Phe Tyr Ile Ser same time Arg Thr gin Lys same time Lys Ala Phe Thr Leu 130 135 140 Lys Thr Leu Lys Ser Phe Lys Leu for gin wall Ser Glu Glu Ser wall 145 150 155 160 Leu Leu Lys Glu Lys Gly Lys for Lys Ala wall Arg Arg Glu Leu wall 165 170 175 Ala Lys Asp Tyr Ala Ile wall Leu gin wall Gly Asp Thr Leu His Asp 180 185 190 Phe Asp Ala Ile Phe Ala Lys Asp Ala Lys same time Ser gin Glu gin gin 195 200 205 Ala Lys wall Leu gin same time Ala gin Lys Phe Gly Thr Glu Trp Ile Ile 210 215 220 Leu for same time Ser Leu Tyr Gly Thr Trp Glu Asp Gly for Ile Lys Ala 225 230 235 240 Trp gin same time Lys Lys 245 (2, INFORMATION > SEQ. No. 5.:135:

(i, SEQUENCE CHARACTERISTICS:

(A) LENGTH: 288 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear

216 (ii) MOLECULA TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE:

(A, ORGANISM: Helicobacter pylori (ix)

(A) NAME / KEY: various characters (B) LOCATION 1 ... 288 (xi) SEQUENCE DESCRIPTION: SEQ. NO. 135:

Leu Trp Cys Leu Lys Thr for Ile Ile Gly His Gly Met Lys Lys Lys 1 5 10 15 Ala Lys wall Phe Trp Cys Cys Phe Lys Met Ile Arg Trp Leu Tyr Leu 20 25 30 Ala wall Phe Phe Leu Leu Ser wall Ser Asp Ala Lys Glu Ile Ala Met 35 40 4 ' » gin Arg Phe Asp Lys gin same time His Lys Ile Phe Glu 111: Leu Ala Asp 50 55 60 Lys wall Ser Ala Lys Asp same time wall Ile Thr Ala Ser Gly same time Ala Ile 65 70 75 80 Leu Leu same time Tyr Asp wall Tyr Ile Leu Ala Asp Lys wall Arg Tyr Asp 85 90 95 Thr Lys Thr Lys Glu Ala Leu Leu Glu Gly same time Ile Lys wall Tyr Arg 100 105 110 Gly Glu Gly Leu Leu wall Lys Thr Asp Tyr wall Lys Leu Ser Leu same time 115 120 125 Glu Lys Tyr Glu Ile Ile Phe for Phe Tyr wall gin Asp Ser wall Ser 130 135 140 Gly Ile Trp wall Ser Ala Asp Ile Ala Ser Gly Lys Asp gin Lys Tyr 145 150 155 160 Lys Ile Lys same time Met Ser Ala Ser Gly Cys Ser Ile Asp same time for Ile 165 170 175 Trp His wall same time Ala Thr Ser Gly Ser Phe same time Met gin Lys Ser His 180 185 190 Leu Ser Met Trp same time for Lys Ile Tyr wall Gly Asp Ile for wall Leu 195 200 205 Tyr Leu for Tyr Ile Phe Met Ser Thr Ser same time Lys Arg Thr Thr Gly 210 215 220 Phe Leu Tyr for Glu Phe Gly Thr Ser same time Leu Asp Gly Phe Ile Tyr 225 230 235 240 Leu gin for Phe Tyr Leu Ala for Lys same time Ser Trp Asp Met Thr Phe 245 250 255 Thr for gin Ile Arg Tyr Lys Arg Gly Phe Gly Leu same time Phe Glu Ala 260 265 270 Arg Tyr Ile same time Ser Lys Thr gin wall Phe Ile gin Cys Ala Leu Phe 275 280 285

(2) INFORMATION ABOUT SEQ. NO. 136:

(i) SEQUENCE CHARACTERISTICS:

(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)

(A) NAME / KEY: different characters

217 (B) LOCATION 1 ... 128

(Xi) SEQUENCE DESCRIPTION: SEQ. NO .: 136: Leu Met Phe Lys Lys Met Cys Leu Ser Leu Leu Met Ile Ser Gly wall 1 5 10 15 Cys wall Gly Ala Lys Asp Leu Asp Phe Lys Leu Asp Tyr Arg Ala Thr 20 25 30 Gly Gly Lys Phe Met Gly Lys Met Thr Asp Ser Ser Leu Leu Ser Ile 35 40 45 Thr Ser Met same time Asp Glu for wall wall Ile Lys same time Leu Ile wall same time 50 55 60 Arg Gly same time Ser Cys Glu Ala Thr Lys Lys wall Glu for Lys Phe Gly 65 70 75 80 Asp Lys Phe Lys Lys Glu Lys Leu Phe Asp His Glu Leu Lys Tyr Ser 85 90 95 gin gin Ile Phe Tyr Arg Leu Asp Cys Lys for same time gin Leu Leu Glu 100 105 110 wall Lys Ile Ile Thr Asp Lys Gly Glu Tyr Tyr His Lys Phe Ser Lys

115 120 125 (2) INFORMATION ABOUT SEQ. NO. 137:

(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) SIGN: (A) NAME / KEY: different characters (B) LOCATION 1 ... 169 (xi) SEQUENCE DESCRIPTION: SEQ. NO. 137: Met Gin Ala Leu Lys Ser Leu Leu Glu Val White Thr Lys Leu Gin Asn 15 10 15 Leu Gly Gly Tyr Leu Met His White Ala White Phe White Phe White Trp 20 25 30 Gly Gly Leu Lys Phe Val Pro Tyr Glu Ala Glu Gly Ala Pro 34 40 45 Phe Val Ala Asn Ser Phr Phe Ser Phe Met Tyr Lys Phe Glu Lys 50 55 60 Lys Gin His Lys Met Ser Glu Ser Gin Ser Gin 65 70 75 80 Glu Met Gin Asp Asn Pro Lys White Glu Asn Lys Glu Trp His Lys 85 Glu Asn Arg Thr Tyr Leu Val Ala Glu Gly Leu Gly White Thr White Met 100 105 110 Leu Gly Leo Leu Val Leu Leu Gly Leu Trp Met For Leu Met Gly 115 120 125 Val Val Gly Gly Leu Leu Val Ala Gly Met Thr ile Thr Thr Leu Phe 129 135 140 Phe Phe His His Asn Ala Arg Ser Val Cys Gin Ser Ala Phe Pro Met 145 150 155 160

Ala Phe Trp Gly Trp Lys Ala Ser Gly 165 (2) SEQ ID NO. NO. 138:

218 (i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 487 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 ... 487 (xi) SEQUENCE DESCRIPTION: SEQ. NO. 138:

Met Ile Glu Trp Met gin same time His Arg Lys Tyr Leu V..1 wall Thr Ile 1 5 10 15 Trp Ile Ser Thr Ile Ala Phe Ile Ala Ala Gly Met ] li> Gly Trp Gly 20 25 30 gin Tyr Ser Phe Ser Leu Asp Ser Asp Ser Ala Ala I.ys wall Gly gin 35 40 ir. Ile Lys Ile Ser gin Glu Glu Leu Ala gin Glu Tyr Arcj Arg Leu Lys 50 55 60 Asp Ala Tyr Ala Glu Ser Ile for Asp Phe Lys Glu Leu Thr Glu Asp 65 70 75 80 gin Ile Lys Ala Met His Leu Glu Lys Ser Ala Leu Asp Ser Leu Ile 85 90 95 same time gin Ala Leu Leu Arg same time Phe Ala Leu Asp Leu Gly Leu Gly Ala 100 105 110 Thr Lys gin Glu wall Ala Lys Glu Ile Arg Lys Thr same time wall Phe gin 115 120 125 Lys Asp Gly wall Phe Asp Glu Glu Leu Tyr Lys same time Ile Leu Lys gin 130 135 140 Ser His Tyr Arg for Lys His Phe Glu Glu Ser wall Glu Arg Leu Leu 145 150 155 160 Ile Leu gin Lys Ile Ser Ala Leu Phe for Lys Thr Thr Thr for Leu 165 170 175 Glu gin Ser Ser Leu Ser Leu tr.po Ala Lys Leu gin A :: p Lys Leu Asp 180 185 190 Ile Leu Ile Leu same time for same time Asp wall Lys Ile Ser Leu same time Glu Glu 195 200 205 Glu Met Lys Lys Tyr Tyr Glu same time His Arg Lys Asp The Lys Lys for 210 215 220 Thr Ser Phe Lys Thr Arg Ser Leu Tyr Phe Asp Ala Ser Leu Glu Lys 225 230 235 240 Thr Asp Leu Lys Glu Leu Glu Glu Tyr Tyr His Lys same time Lys wall Ser 245 250 255 Tyr Leu Asp Lys Glu Gly Lys Leu gin Asp Phe Lys Ser wall gin Glu 260 265 270 gin wall Lys His Asp Leu same time Met gin Lys Aia same time Glu Lys Ala Leu 275 280 285 Arg Ser Tyr Ile Ala Leu Lys Lys Gly same time Ala gin same time Tyr Thr Thr 290 295 300 gin Asp Phe Glu Lys same time same time Ser for Tyr Thr Ala Glu Ile Thr gin 305 310 315 320 Lys Leu Thr Ala Leu Lys for Leu Glu wall Leu Lys for Glu for Phe 325 330 335 Lys Asp Gly Phe Ile wall wall gin Leu wall Ser gin Ile Lys Asp Glu 340 345 350 Leu gin same time Phe Asp Glu Ala Lys Ser Ala Leu Lys Thr Arg Leu Thr 355 360 365 gin Glu Lys Thr Leu Met Ala Leu gin Thr Leu Ala l.ys Glu Lys Leu 370 375 380

219

Lys Asp Phe Lys Gly Lys Ser wall Gly Tyr wall Ser for same time Phe Gly 385 390 395 400 Gly Thr Ile Ser Glu Leu same time gin Glu Glu Ser Ala Lys Phe Ile same time 405 410 415 Thr Leu Phe same time Arg gin Glu Lys Lys Gly Phe wall Thr Ile Gly same time 420 425 430 Lys wall wall Leu Tyr gin Ile Thr Glu gin same time Phe same time His for Phe 435 440 445 Ser Ala Glu Glu same time gin Tyr Met gin Arg Leu wall same time same time Thr Lys 450 455 4 60 Thr Asp Phe Phe Asp Lys Ala Leu Ile Glu Glu Leu Lys Lys Arg Tyr 465 470 475 480 Lys Ile wall Lys Tyr Ile gin

485 (2) INFORMATION ABOUT SEQ. NO. 139:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 142 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: : various characters (B) LOCATION. .. .142 (Xi) SEQUENCE DESCRIPTION: SEQ. no. :: L39: Met Lys Thr Asn Phe Tyr Lys Ile Lys Leu Leu Phe Ala Trp Cys Leu 1 5 10 15 Ile Ile Gly Met Phe Asn Ala for Leu same time Ala Asp gin same time Thr Asp 20 25 30 Ile Lys Asp Pro Ser Pro Glu Asp Met Ala Leu same time Ser wall Gly Leu 35 40 45 wall Ser Arg Asp Gin Leu Lys Ile Glu Ile for Lys Glu Thr Leu Glu 50 55 60 gin Lys Val Ala Leu same time Asp Tyr same time Asp Lys same time wall same time Ile 65 70 75 80 Lys Phe Asp Asp J Ser Ser Leu Gly Ser Phe gin for same time Asp same time Leu 85 90 95 Gly Ile Asn Ala Met Trp Gly Ile gin same time Leu Leu Met Ser gin Met 100 105 110 Met Ser Asn Tyr Gly Pro same time same time Ser Phe Met Tyr Gly Tyr Ala for 115 120 125 Thr Tyr Ser Asp Ser Ser Phe Leu for for Ile Leu Gly Tyr 130 135 140

(2) INFORMATION ABOUT SEQ. NO. 140:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 208 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULA TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE:

220 (A, ORGANISM: Helicobacter pylori (ix)

(A, NAME / KEY: various characters (B) LOCATION 1 ... 208 (xi, SEQUENCE DESCRIPTION: SEQ ID NO: 140:

Leu Ile same time same time same time same time same time same time Lys Lys Leu Arg Gly Phe Phe Leu 1 5 10 15 Lys wall Leu Leu Ser Leu wall wall Phe Ser Ser Tyr Gly Ser Ala same time 20 25 30 Asp Asp Lys Glu Ala Lys Lys Glu Ala Leu Glu Lys Glu I.ys same time Thr 35 40 45 for same time Gly Leu wall Tyr Thr same time Leu Asp Phe Asp Ser Phe Lys Ala 50 55 60 Thr Ile Lys same time Leu Lys Asp Lys Lys wall Thr Phe Lys Glu wall same time 65 70 75 80 for Asp Ile Ile Lys Asp Glu wall Phe asd Phe wall Ile wall same time Arg 85 90 95 wall Leu Lys Lys Ile Lys Asp Leu Lys His Tyr Asp for wall Ile Glu 100 105 110 Lys Ile Phe Asp Glu Lys Gly Lys Glu Met Gly Leu same time wall Glu Leu 115 120 12.5 gin Ile same time for Glu wall Lys Asp Phe Phe Thr Phe Lys Ser Ile Ser 130 135 140 Thr Thr same time Lys gin Arg Cys Phe Leu Ser Leu His Gly Glu Thr Arg 145 150 155 160 Glu Ile Leu Cys Asp Asp Lys Leu Tyr same time wall Leu Leu Ala wall Phe 165 170 175 same time Ser Tyr Asp for same time Asp Leu Leu Lys His Ile Ser Thr Ile Glu 180 185 190 Ser Leu Lys Lys Ile Phe Tyr Thr Ile Thr Cys Glu Ala wall Tyr Leu

195 200 205 (2) INFORMATION ABOUT SEQ. ¢.: 141:

(i, SEQUENCE CHARACTERISTICS:

(A) LENGTH: 245 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear

(Ii. MOLECULA TYPE: protein (Iii. HYPOTHETICAL: YES (See, ORIGINAL SOURCE: (A) ORGANISM: Helicobacter pylo: ri (Ix, SIGN: (A) NAME / KEY: various; letters (B, LOCATION 1. . . .245 (Xi. SEQUENCE DESCRIPTION: SEQ. No. :: L41: Met Ala Gly Thr Gin Ala White Tyr Glu Ser Ser Ser Ala Gly Phe Leu 1 5 10 15 Ser gin Val Ser Ser ile ile Ser Ser Thr Ser Gly wall Ala Gly for 20 25 30 Phe Ala Gly White Val Ala Gly Ala Met Thr Ala Ala Ile Ile for Ile 35 40 45 wall wall Gly Phe Thr gin Met Thr Ala Ile Met Thr gin Tyr 50 55 60 same time gin Ala Ala Glu Ala wall Ser wall for Met Lys Ala Ala same time 65 70 75 80 gin gin Tyr Asn Gin Leu Tyr gin Gly Phe same time Asp gin Ser Met Ala

221

85 90 95 wall Gly same time same time Ile Leu same time Ile Ser Lys Leu Thr Gly Glu Phe same time 100 105 110 Ala gin Gly same time Thr gin Ser Ala gin Ile Ser Ala wall same time Ser gin 115 120 125 Ile Ala Ser Ile Leu Ala Ser same time Thr Thr for Lys same time for Ser Ala 130 135 140 Ile Glu Ala Tyr Ala Thr same time gin Ile Ala wall for Ser wall for Thr 145 150 155 160 Thr wall Glu Met Met Ser Gly Ile Leu Gly same time Ile Thr Ser Ala Ala 165 170 175 for Lys Tyr Ala Leu Ala Leu gin Glu gin Leu Arg Ser gin Ala Ser 180 185 190 same time Ser Ser Met same time Asp Thr Ala Asp Ser Leu Asp Ser Cys Thr Ala 195 200 205 Leu Gly Ala Leu wall Gly Ser Ser Lys wall Phe Phe Ser Cys Met gin 210 215 220 Ile Ser Met Thr for Met Ser wall Ser mec for Thr wall Met for same time 225 230 235 240 Thr Ser Gly Cys His 245

(2) INFORMATION ABOUT SEQ. NO. 142:

(1) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 367 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 ... 367 (xi) SEQUENCE DESCRIPTION: SEQ. NO. 142:

Met Ile Lys Ser wall Glu Ile Glu same time Tyr Lys same time Phe Glu His Leu 1 5 10 15 Lys Met Glu same time Phe Lys Leu Ile same time Phe Phe Thr Gly gin same time Asp 20 25 30 Ala Gly Lys Thr same time Leu Leu Glu Ala Leu Tyr Thr same time Thr Gly Leu 35 40 45 Cys Asp for Thr Ala same time gin wall Ser Leu for for Glu His Ala wall 50 55 60 same time Ile Ser Glu Phe Arg Lys Ile Lys Leu Asp Ala Asp same time Leu Lys 65 70 75 80 Thr Phe Phe Tyr gin Gly same time Thr Ala same time for Ile Ser Ile Arg Thr 85 90 95 Glu Phe Glu His Ala Thr Ile for Leu Thr Ile gin Tyr for Thr gin 100 105 110 Thr Ser Tyr Ser Lys Asp Ile same time Leu same time Ser Asp Asp Ala His Met 115 120 125 Thr same time Leu Ile same time Thr Thr Ile Thr Lys for gin Leu gin Phe Ser 130 135 140 Tyr same time for Ser Leu Ser for Met Thr Met Thr Tyr Glu Phe Glu Arg 145 150 155 160 gin same time Leu Gly Leu Ile His Ser same time Leu Asp Lys Ile Ala gin Thr 165 170 175 Tyr Lys Glu same time Ala Met Phe Ile for Ile Glu Leu Ser Ile wall same time 180 185 190

222

Ser Leu Lys Ala Leu Glu Asn Leu Gin Leu Ala Glu Lys Glu 195 200 205 Leu Ile Glu Ile Leu gin Cys Phe same time for same time Ile Leu same time Ala same time 210 215 220 Thr Ile Arg Lys Ser wall Tyr Ile gin Ile Lys Asp Glu same time Thr for 225 230 235 240 Leu Glu Glu Ser for Lys Arg Leu Leu same time Leu Phe Gly Trp Gly Phe 245 250 255 Ile Lys Phe Phe Ile Met wall Ser Ile Leu Ile Asp same time Arg wall Lys 260 265 270 Tyr Leu Phe Ile Asp Glu Ile Glu Ser Gly Leu His His Thr Lys Met 275 280 285 gin Glu Phe Leu Lys Ala Leu Phe Lys Leu Ala gin Lys Leu gin Ile 290 295 300 gin Ile Phe Ala Thr Thr His same time Lys Glu Phe Leu Leu same time Ala Ile 305 310 315 320 same time Thr Ile Ser Asp same time Glu Thr Gly wall Phe Lys Asp Ile Ala Leu 325 330 335 Phe Glu Leu Glu Lys Glu Ser Ala Ser Gly Phe Ile Arg His Ser Tyr 340 345 350 Ser Met Leu Glu Lys Ala Leu Tyr Arg Gly Met Glu wall Arg Gly

355 360 365 (2) INFORMATION ABOUT SEQ. NO. 143:

(1) SEQUENCE CHARACTERISTICS:

(A, LENGTH: 409 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear

(ii) MOLECULA TYPE: protein (Iii) HYPOTHETICAL: YES (See, ORIGINAL SOURCE: (A) ORGANISM: Helicobacter pylori (Ix) SIGN: (A) NAME / KEY : Differently ; letters (B) LOCATION ... 409 (Xi) SEQUENCE DESCRIPTION: SEQ. No. :: L43: Met Ser Leu ile Arg wall same time Gly Glu Ala Phe Lys Leu Ser Leu Glu 1 5 10 15 Ser Leu Glu Glu Asp for Phe Glu Thr Lys Glu Thr Leu Glu Thr Leu 20 25 30 Glu Thr Leu ile Lys gin Thr Ser wall wall Leu Leu Ala Ala Gly Glu 35 40 45 Ser Lys Arg Phe Ser Arg Ala Ile Lys Lys gin Trp Leu Arg Ser His 50 55 60 His Thr Pro Leu Trp Leu Ser wall Tyr Glu Ser Phe Lys Glu Ala Leu 65 70 75 80 Asp Phe Lys Glu wall Ile Leu wall wall Ser Glu Leu Asp Tyr wall Tyr 85 90 95 Ile gin Arg His Tyr for Lys Ile Lys Leu wall Lys Gly Gly Ala Ser 100 105 110 Arg gin Glu Ser wall Arg same time Ala Leu Lys wall Ile Asp Ser Thr Tyr 115 120 125 Thr Ile Thr Ser Asp wall Ala Arg Gly Leu Ala same time Met Glu Ala Leu 130 135 140 Lys Ser Leu Phe Leu Thr Leu gin gin Thr Ser His Tyr Cys Ile Ala 145 150 155 160 for Tyr Leu Pro Cys Tyr Asp Thr Ala Ile Tyr Tyr same time Glu Ala Leu 165 170 175 Asp Arg Glu Ala Ile Lys Leu Ile gin Thr for gin Leu Ser His Thr

223

180 185 190 Lys Thr Leu gin Ser Ala Leu same time gin Gly Gly Phe Lys Asp Glu Ser 195 200 205 Ser Ala Ile Leu gin Ala Phe for same time Ser wall Ser Tyr Ile Glu Gly 210 215 220 Ser Lys Asp Leu His Lys Leu Thr Thr Ser Gly Asp Leu Lys Phe Phe 225 230 235 240 Thr for Phe Phe same time for Ala Lys Asp Thr Phe Ile Gly Met Gly Phe 245 250 255 Asp Thr His Ala Phe Ile Lys Asp Lys for Met wall Leu Gly Gly wall 260 265 270 wall Leu Asp Cys Glu Phe Gly Leu Lys Ala His Ser Asp Gly Asp Ala 275 280 285 Leu Leu His Ala wall Ile Asp Ala Ile Leu Gly Ala Ile Lys Gly Gly 290 295 300 Asp Ile Gly Glu Trp Phe for Asp same time Asp for Lys Tyr Lys same time Ala 305 310 315 320 Ser Ser Lys Glu Leu Leu Lys Ile wall Leu Asp Phe Ser gin Ser Ile 325 330 335 Gly Phe Glu Leu Leu Glu Met Gly Ala Thr Ile Phe Ser Glu Ile for 340 345 350 Lys Ile Thr for Tyr Lys for Ala Ile Leu Glu same time Leu Ser gin Leu 355 360 365 Leu Gly Leu Glu Lys Ser gin Ile Ser Leu Lys Ala Thr Thr Met Glu 370 375 380 Lys Met Gly Phe Ile Gly Lys gin Glu Gly Leu Leu wall gin Ala His 385 390 395 400 wall Ser Met Arg Tyr Lys gin Lys Leu

405 (2) INFORMATION ABOUT SEQ. NO. 144:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 270 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: various; letters (B) LOCATION. , 270 .. (Xi) SEQUENCE DESCRIPTION: SEQ. no. :: L44: Met Lys Lys Phe Gly Leu Leu Ser Ala wall Leu Ser Ser 1 5 10 15 Ser Leu Leu Ala Glu Gly Asp Gly wall Tyr Ile Gly Thr same time Tyr gin 20 25 30 Leu Gly Gin Ala Arg Leu Asn Ser same time Ile Tyr same time Thr Gly Asp Cys 35 40 45 Thr Gly Ser Val Val for for Gly Leu Thr Ala same time Lys His 50 55 60 same time for Gly Gly Thr Asn White same time Trp His Ser Lys Tyr Ala same time Gly 65 70 75 80 Ala Leu Asn Gly Phe Gly Leu same time wall Gly Tyr Lys Lys Phe Phe gin 85 90 95 Phe Lys Ser Leu Asp Met Thr Ser Lys Trp Phe Gly Phe Arg wall Tyr 100 105 110 Gly Leu Phe Asp Tyr Gly His Ala Asp Leu Gly Lys gin wall Tyr Ala 115 120 125

224

for Asn Lys White Gin Leu Asp Met Val Ser Trp Gly Val Gly Ser Asp 130 135 Leu Leu Ala Asp Ile Ile Asp Lys Asp same time Ala Ser Phe Gly Ile Phe 145 150 155 160 Gly Gly wall Ala Ile Gly Gly same time Thr Trp Lys Ser Ser Ala Ala same time 165 170 175 Tyr Trp Lys Glu gin Ile Ile Glu Ala Lys Gly for Asp wall Cys Thr 180 185 190 for Thr Tyr Cys same time for same time Ala for Tyr Ser Thr same time Thr Ser Thr 195 200 205 wall Ala Phe gin wall Trp Leu same time Phe Gly wall Arg Ala same time Ile Tyr 210 215 220 Lys His same time Gly wall Glu Phe Gly wall Arg wall for Leu Leu Ile same time 225 230 235 240 Lys Phe Leu Ser Ala Gly for same time Ala Thr same time Leu Tyr Tyr His Leu 245 250 255 Lys Arg Asp Tyr Ser Leu Tyr Leu Gly Tyr same time Tyr Thr Phe

260 265 270 (2, SEQ ID NO: 145:

(1) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 438 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, LOCATION 1 ... 438 (Xi) SEQUENCE DESCRIPTION: SEQ. NO. 145: Met Ala Tyr Lys For Asn Lys Lys Lys 1 5 10 15 for same time Leu Phe Ser I Leu Asp Lys Gly Asp Val Ala Thr Asn Asn 20 25 30 for wall Glu Glu Ser Asp Lys Ala Asn Lys White Gin Glu Pro Leu Pro 34 40 45 Tyr wall Val Lys Thr Gin White Asn Lys Ala Ser Met White Ser Arg Asp 50 55 60 for Ile Glu Trp Ala Lys Tyr Leu Ser Phe 65 70 Asp same time Ser Lys Glu Asp Val Asn Phe Phe Ala Asn Gly Glu Lys 85 Glu Ser Ser Arg Val Glu Glu Ala Asn Lys Glu Gly Arg Arg 100 105 110 Ile Thr Lys Arg Tyr Asp Leu ile Asp Arg Asn Ile Asp Arg Asn Arg 115 120 125 Glu Phe Phe Lys Glu White Glu White Leu Thr His Thr Asn Ser Leu 130 135 140 Lys Glu Leu Lys Glu Gly Leu Glu White Gin Leu Thr His His Asn 145 150 155 160 Glu Thr His Lys Lys Ala Glu Asn Gly Asn Glu White Val Lys Glu 165 170 175 Tyr Asp His Leu Lys Asps Tyr Gin Glu Val Glu Arg Thr Lys Asp 180 185 190 Gly Gly Leu Val Arg Glu White Ser Pro Ser Ser Ala Glu Tyr 195 200 205 Phe Lys Leu Tyr Asn Lys Leu Pro Phe Glu Ser J Asn Asn Glu Asn

225

210 215 220 Thr Lys Leu same time Thr same time Asp same time Glu Glu wall Lys Lys Leu Glu Phe 225 230 235 240 Glu Leu Ala Lys Glu wall His Ile Leu Ile Leu Glu gin gin Leu Leu 245 250 255 Ser Ala Thr same time Tyr Tyr Ser Trp Ile Asp Lys Asp Asp same time Ala same time 260 265 270 Phe Ala Trp Lys Met His Arg Leu Ile same time Glu same time Lys Leu Lys Glu 275 280 285 same time His Leu Ser Ala same time same time Ala same time Lys Ile Lys gin Phe Phe Phe 290 295 300 same time same time Gly Ser Ile Leu Gly Trp Thr Lys Glu Glu gin Ser Ala Ile 305 310 315 320

Gin Glu Asn

(+420) 325 330 335

Glu ile Ala Gin Ala Lys Ile Glu Leu Gin Lys Tyr Glu Ser Val 345 350 Tyr wall same time Gly Asp Gly same time Lys Arg Glu Ile Lys for Phe Lys Glu 355 360 365 Ile Leu Arg Asp Thr same time same time Phe Glu Lys Ala Tyr Lys Glu Arg Tyr 370 375 380 Asp Lys Leu wall Ser Leu Ser Ala Ala Ile Ile gin Ala Lys Glu Gly 385 390 395 400 Gly same time Glu Arg for same time Ser Ser Ala same time same time same time same time for Ile Lys 405 410 415 same time Thr Ile Glu Thr same time Thr Ser same time same time Ile Ile gin same time same time Asp 420 425 430 same time Ile Ile Ile gin Ile 435

(2) INFORMATION ABOUT SEQ. NO. 146:

(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) NAME / KEY: various characters (B) LOCATION 1 ... 215 (xi) SEQUENCE DESCRIPTION: SEQ. NO. 146:

Met 1 Gin Ala Leu Lys 5 Ser Leu Leu Glu wall 10 Ile Thr Lys Leu gin 15 same time Leu Gly Gly Tyr 20 Leu Met His Ile Ala 25 Ile Phe Ile Ile Phe 30 Ile Trp Ile Gly Gly Leu Lys Phe wall for 40 Tyr Glu Ala Glu Gly 45 Ile Ala for Phe Val Ala same time Ser for Phe 55 Phe Ser Phe Met Tyr 60 Lys Phe Glu Lys for 65 Ala Tyr Lys gin His 70 Lys Met Ser Glu Ser 75 gin Ser Met gin Glu 80 Glu Met Gin Asp same time 85 for Lys Ile wall Glu 90 same time Lys Glu Trp His 95 Lys Glu Asn Arg Thr 100 Tyr Leu wall Ala Glu 105 Gly Leu Gly Ile Thr 110 Ile Met Ile Leu Gly Ile Leu wall Leu Leu 120 Gly Leu Trp Met for 125 Leu Met Gly

226

wall Val Gly Gly Leu Leu Val Ala Gly Met Thr Thr Thr Thr Leu Ser 130 135 140 Phe Leu Phe Thr Thr for Glu wall Phe wall same time gin His Phe for Trp 145 150 155 160 Leu Ser Gly Ala Gly Arg Leu wall wall Lys Asp Leu Ala Leu Phe Ala 165 170 175 Gly Gly Leu Phe wall Ala Gly Phe Asp Ala Lys Arg Tyr Leu Glu Gly 180 185 190 Lys Gly Phe Cys Leu Met Asp Arg Ser Ser wall Gly Ile Lys Thr Lys 195 200 205 Cys Ser Ser Gly Cys Cys Ser 210 215

(2) INFORMATION ABOUT SEQ. NO. 147:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 20 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 ... 20 (xi) SEQUENCE DESCRIPTION: SEQ. No .-. 147:

TATACCATGG TGGGCGCTAA 20 (2) INFORMATION ABOUT SEQ. NO. 148:

(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: SEQ ID NO: 148:

ATGAATTCGA GTAAGGATTT TTG 23 (2, SEQ ID NO: 149:

(i) SEQUENCE CHARACTERISTICS:

227 (A) LENGTH: 22 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 ... 22 (xi) SEQUENCE DESCRIPTION: SEQ. NO. 149:

TTAACCATGG TGAAAAGCGA TA 22 (2) INFORMATION ABOUT SEQ. NO. 150:

(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) NAME / KEY: various characters (B) LOCATION 1 ... 23 (xi) SEQUENCE DESCRIPTION: SEQ. NO. 150:

TAGAATTCGC ATAACGATCA ATC 23 (2) INFORMATION ABOUT SEQ. NO. 151:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 22 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

228 (B) LOCATION 1 ... 22 (xi, SEQUENCE DESCRIPTION: SEQ ID NO: 151:

ATATCCATGG TGAGTTTGAT GA 22 (2) SEQ ID NO. NO. 152:

(i, SEQUENCE CHARACTERISTICS:

(A) LENGTH: 25 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D, TOPOLOGY: circular (ii) MOLECULAR TYPE: ONE (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: SEQ ID NO: 152:

ATGAATTCAA TTTTTTATTT TGCCA 25 (2) SEQ ID NO. NO. 153:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 21 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 ... 21 (xi) SEQUENCE DESCRIPTION: SEQ. NO. 153:

AATTCCATGG TGGGGGCTAT G 21 (2) SEQ ID NO. NO. 154:

(i) SEQUENCE CHARACTERISTICS:

(A, LENGTH: 23 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular (ii, MOLECULA TYPE: DNA (genomic,

229

(Iii) HYPOTHETICAL: NO (Iv. ANTI-SENSE: NO (Vi) ORIGINAL SOURCE: (A) ORGANISM: Helicobacter (Ix, SIGN: (A) NAME / KEY: different characters (B) LOCATION 1 ... 23 (Xi. SEQUENCE DESCRIPTION: SEQ. No. 154 ATGAATTCTC GATAGCCAAA ATC (2, INFORMATION 0 SEQ ID NO: i 155:

(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: SEQ. NO. 155:

AATTCCATGG TGCATAACTT CCATT (2) SEQ ID NO. NO. 156:

(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, SIGN: (A) NAME / KEY: different characters (B) PLACEMENT 1 ... 25 (Xi. DESCRIPTION i SEQUENCES: SEQ. NO. 156:

AAGAATTCTC TAGCATCCAA ATGGA (2) INFORMATION ABOUT SEQ. NO. 157:

230 (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: SEQ. NO. 157:

ATTTCCATGG TCATGTCTCA TATT 24 (2) SEQ ID NO. NO. 158:

(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) NAME / KEY: various characters (B) LOCATION 1 ... 23 (xi) SEQUENCE DESCRIPTION: SEQ. NO. 158:

ATGAATTCCA TCTTTTATTC CAC 23 (2) SEQ ID NO. NO. 159:

(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

231 (ix) SIGN:

(A, NAME / KEY: various characters (B) LOCATION 1 ... 27 (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 159:

AACCATGGTG ATTTTAAGCA TTGAAAG 27 (2) INFORMATION ABOUT SEQ. No ..- 160:

(i, SEQUENCE CHARACTERISTICS:

(A) LENGTH: 28 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 ... 28 (xi, SEQUENCE DESCRIPTION: SEQ ID NO: 160:

AAGAATTCCA CTCAAAATTT TTTAACAG 28 (2) SEQ ID NO. No ..- 161:

(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 (iv) ANTI-SENSE : NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) NAME / KEY: various characters (B) LOCATION 1 ... 25 (xi) SEQUENCE DESCRIPTION: SEQ. NO. 161:

GATCATCCAT ATGTTATCTT CTAAT 25 (2, SEQ ID NO: 162:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 23 base pairs (B, TYPE: nucleic acid (C) FIBER NUMBER: two (D) TOPOLOGY: circular

232 (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: SEQ. NO. 162:

TGAATTCAAC CATTTTAACC CTG 23 (2) SEQ ID NO. NO. 163:

(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 (ix)

(A) NAME / KEY: various characters (B) LOCATION 1 ... 27 (xi) SEQUENCE DESCRIPTION: SEQ. NO. 163:

TATACCATGG TGAAATTTTT TCTTTTA 27 (2) INFORMATION ABOUT SEQ. NO. 164:

(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 (iv, ANTI-SENSE) : NO (vi, ORIGINAL SOURCE:

(A, ORGANISM: Helicobacter pylori (ix) SIGN £ (A) NAME / KEY: different characters (B, PLACEMENT 1 .. .25

(xi, SEQUENCE DESCRIPTION: SEQ ID NO: 164:

AGAATTCAAT TGCGTCTTGT AAAAG

233 (2) INFORMATION ABOUT SEQ. NO. 165:

(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: SEQ. NO. 165:

TATACCATGG TGATGGACAA ACTC 24 (2) SEQ ID NO. NO. 166:

(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) NAME / KEY: various characters (B) LOCATION 1 ... 23 (xi) SEQUENCE DESCRIPTION: SEQ. NO. 166:

ATGAATTCCC ACTTGGGGCG ATA 23 (2) INFORMATION 0 SEQ. NO. 167:

(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:

234 (A) ORGANISM: Helicobacter pylori (ix)

(A) NAME / KEY: various characters (B) LOCATION 1 ... 25 (xi) SEQUENCE DESCRIPTION: SEQ. NO. 167:

TTATGGATCC AAACCAATTA AAACT 25 (2) INFORMATION 0 SEQ. NO. 168:

(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 (Ix) SIGN: (A) NAME / KEY:: (B) LOCATION various characters 1 ... 23 (Xi) SEQUENCE DESCRIPTION: SEQ. No. 168 TATCTCGAGT TATAGAGAAG GGC (2) INFORMATION 0 SEQ. No. : 169:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 22 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 ... 22 (xi) SEQUENCE DESCRIPTION: SEQ. NO. 169:

TTAACCATGG TGAAAAGCGA TA 22 (2) INFORMATION ABOUT SEQ. NO. 170:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 24 base pairs (B) TYPE: nucleic acid (C) FIBER NUMBER: two

235 (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: SEQ ID NO: 170:

TAGAATTCGC CTCTAAAACT TTAG (2) SEQ ID NO. NO. 171:

(i, SEQUENCE CHARACTERISTICS:

(A, LENGTH: 22 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 ... 22 (xi, SEQUENCE DESCRIPTION: SEQ ID NO: 171:

TTAACCATGG TGAAAAGCGA TA (2) INFORMATION ABOUT SEQ. NO. 172:

(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, SIGN:

(A) NAME / KEY: various characters (B) LOCATION 1 ... 23 (xi, SEQUENCE DESCRIPTION: SEQ ID NO: 172:

236

TAGAATTCGC ATAACGATCA ATC 23 (2) INFORMATION ABOUT SEQ. NO. 173:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 22 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 ... 22 (xi) SEQUENCE DESCRIPTION: SEQ. NO. 173:

ATATCCATGG TGAGTTTGAT GA 22 (2) INFORMATION 0 SEQ. NO. 174:

(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: SEQ. NO. 174:

ATGAATTCAA TTTTTTATTT TGCCA 25 (2) SEQ ID NO. NO. 175:

(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 : NOT

237

(vi) ORIGINAL SOURCE: Helicobacter pylori (A) ORGANISM: (Ix) SIGN: (A) NAME / KEY: (B) LOCATION different characters 1. .23 (Xi) SEQUENCE DESCRIPTION: SEQ. NO. 175:

AATTCCATGG CTATCCAAAT CCG 23 (2) SEQ ID NO. NO. 176:

(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: SEQ. NO. 176:

ATGAATTCGC CAAAATCGTA GTATT 25 (2) INFORMATION ABOUT SEQ. NO. 177:

(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: SEQ. NO. 177:

GATACCATGG AATTTATGAA AAAG 24 (2) INFORMATION 0 SEQ. NO. 178:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 25 base pairs

238 (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: SEQ. NO. 178:

TGAATTCGAA AÄAGTGTAGT TATAC 25 (2) INFORMATION ABOUT SEQ. NO. 179:

(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)

(A) NAME / KEY: various characters (B) LOCATION 1 ... 19 (xi) SEQUENCE DESCRIPTION: SEQ. NO. 179:

CCCTTCATTT TAGAAATCG 19 (2) SEQ ID NO. NO.: 180:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 20 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 ... 20

239 (xi) SEQUENCE DESCRIPTION: SEQ. NO.: 180:

ATTTCAACCA ATTCAATGCG 20 (2) INFORMATION ABOUT SEQ. NO. 181:

(i) SEQUENCE CHARACTERISTICS:

(A, LENGTH: 20 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 ... 20 (xi) SEQUENCE DESCRIPTION: SEQ. NO. 181:

GCCCCTTTTG ATTTGAAGCT 20 (2) SEQ ID NO. NO. 182:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 22 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 ... 22 (xi) SEQUENCE DESCRIPTION: SEQ. NO. 182:

TCGCTCCAAG ATACCAAGAA GT 22 (2) INFORMATION ABOUT SEQ. NO. 183:

(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

240 (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE:

(A) ORGANISM: Helicobacter pylori (ix)

(A) NAME / KEY: various characters (B) LOCATION 1 ... 22 (xi) SEQUENCE DESCRIPTION: SEQ. NO: 183: CTTGAATTAG GGGCAAAGAT CG (2) INFORMATION ABOUT SEQ. NO. 184:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 22 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 ... 22

(xi) SEQUENCE DESCRIPTION: SEQ. NO. 184:

ATGCGTTTTT ACCCAAAGAA GT (2) SEQ ID NO. NO. 185:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 22 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 ... 22 (xi) SEQUENCE DESCRIPTION: SEQ. NO. 185:

ATAACGCCAC TTCCTTATTG GT (2) SEQ ID NO. NO. 186:

241 (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)

(A) NAME / KEY: various characters (B) LOCATION 1 ... 19 (xi, SEQUENCE DESCRIPTION: SEQ ID NO: 186:

CTTTGGGTAA AAACGCATC 19 (2, SEQ ID NO: 187:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 20 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 ... 20 (xi, SEQUENCE DESCRIPTION: SEQ ID NO: 187:

CGATCTTTGA TCCTAATTCA 20 (2) INFORMATION ABOUT SEQ. NO. 188:

(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, SIGN:

242 (A, NAME / KEY: various characters (B) LOCATION 1 ... 19 (xi, SEQUENCE DESCRIPTION: SEQ ID NO: 188:

ATCAAGTTGC CTATGCTGA 19 (2) SEQ ID NO. NO. 189:

(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: SEQ ID NO: 189:

TTGAACACTT TTGATTATGC GG 22 (2, SEQ ID NO: 190:

(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) NAME / KEY: various characters (B, LOCATION 1 ... 23 (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 190:

GGATTATGCG ATTGTTTTAC ÄAG 23 (2) INFORMATION ABOUT SEQ. NO. 191:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 21 base pairs (B, TYPE: nucleic acid (C, FIBER NUMBER: two (D, TOPOLOGY: circular (ii, MOLECULA TYPE): DNA (genomic,

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

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

(A) NAME / KEY: various characters (B) LOCATION 1 ... 21 (xi) SEQUENCE DESCRIPTION: SEQ. NO. 191:

GTCTTTAGCA AAAATGGCGT C 21 (2) INFORMATION ABOUT SEQ. NO. 192:

(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: various characters (B) LOCATION 1 ... 21 (xi) SEQUENCE DESCRIPTION: SEQ. NO. 192:

AATGAGCGTA AGAGAGCCTT C 21 (2) INFORMATION ABOUT SEQ. NO. 193:

(i, SEQUENCE CHARACTERISTICS:

(A) LENGTH: 18 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 ... 18 (xi, SEQUENCE DESCRIPTION: SEQ ID NO: 193:

CTTATGGGGG TATTGTCA 18

244 (2) INFORMATION ABOUT SEQ. NO. 194:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 18 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 ... 18 (xi) SEQUENCE DESCRIPTION: SEQ. NO. 194:

AGCATGTGGG TATCCAGC 18 (2) SEQ ID NO. NO. 195:

(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)

(A) NAME / KEY: various characters (B) LOCATION 1 ... 19 (xi) SEQUENCE DESCRIPTION: SEQ. No ..- 195:

AGGTTGTTGC CTAAAGACT 19 (2) SEQ ID NO. NO. 196:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 18 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

245 (ix) SIGN:

(A) NAME / KEY: various characters (B) LOCATION 1 ... 18 (xi, SEQUENCE DESCRIPTION: SEQ ID NO: 196:

CTGCCTCCAC CTTTGATC 18 (2) SEQ ID NO. NO. 197:

(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)

(A) NAME / KEY: various characters (B) LOCATION 1 ... 19 (xi, SEQUENCE DESCRIPTION: SEQ ID NO: 197:

ACCAATATCA ATTGGCACT 19 (2) INFORMATION ABOUT SEQ. NO. 198:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 18 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 ... 18 (xi) SEQUENCE DESCRIPTION: SEQ. NO. 198:

ACTTGGAAAA GCTCTGCA 18 (2) INFORMATION ABOUT SEQ. NO. 199:

(i) SEQUENCE CHARACTERISTICS:

(A, LENGTH: 19 base pairs (B, TYPE: nucleic acid (C, FIBER NUMBER: two (D) TOPOLOGY: circular

246 (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 ... 19 (xi, SEQUENCE DESCRIPTION: SEQ ID NO: 199:

CTTGCTTGTC ATATCTAGC 19 (2, SEQ ID NO: 200:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 18 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 ... 18 (xi) SEQUENCE DESCRIPTION: SEQ. NO. 200:

GTTGAAGTGT TGGTGCTA 18 (2, SEQ ID NO: 201:

(i) SEQUENCE CHARACTERISTICS:

(Ά) 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: SEQ. NO. 201:

247

CAAGCAAGTG GTTTGGTTTT AG (2) INFORMATION ABOUT SEQ. NO. 202:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 22 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 ... 22 (xi) SEQUENCE DESCRIPTION: SEQ. NO. 202:

TGGAAAGAGC AAATCATTGA AG 22 (2) INFORMATION ABOUT SEQ. NO. 203:

(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: various characters (B) LOCATION 1 ... 21 (xi) SEQUENCE DESCRIPTION: SEQ. NO. 203:

GCCCATAATC AAAAAGCCCA T 21 (2) INFORMATION ABOUT SEQ. No. 204:

(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 : NOT

248 (vi) ORIGINAL SOURCE:

(A, ORGANISM: Helicobacter pylori (ix)

(A) NAME / KEY: various characters (B) LOCATION 1 ... 24 (xi) SEQUENCE DESCRIPTION: SEQ. No. 204:

CTAAAACCAA ACCACTTGCT TGTC 24 (2) INFORMATION 0 SEQ. NO. 205:

(i) SEQUENCE CHARACTERISTICS:

(A, LENGTH: 16 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 ... 16 (xi) SEQUENCE DESCRIPTION: SEQ. NO. 205:

GTAAAACGAC GGCCAG 16 (2) INFORMATION ABOUT SEQ. No. 206:

(i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 17 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 ... 17 (xi, SEQUENCE DESCRIPTION: SEQ ID NO: 206:

CAGGAAACAG CTATGAC 17 (2) INFORMATION ABOUT SEQ. NO. 207:

(i, SEQUENCE CHARACTERISTICS:

(A, LENGTH: 21 base pairs (B) TYPE: nucleic acid

249 (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 SIGN: (A, NAME / KEY: different characters (B, PLACEMENT 1. .21

(xi) SEQUENCE DESCRIPTION: SEQ. NO. 207:

ATCTTACCTA TCACCTCAAA T 21 (2) INFORMATION ABOUT SEQ. NO. 208:

(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) SIGN: (A, NAME / KEY: different characters (B, PLACEMENT 1 ... 21

(xi, SEQUENCE DESCRIPTION: SEQ ID NO: 208:

AGACAGCAAC ATCTTTGTGA A

Claims (65)

PATENT CLAIMS An isolated nucleic acid comprising a nucleotide sequence encoding an H. pylori polypeptide that is at least about 60% homologous to an amino acid sequence selected from the group consisting of SEQ. NO: 74 to SEQ. NO: 146. An isolated nucleic acid comprising a nucleotide sequence encoding a H. pylori polypeptide selected from the group consisting of SEQ. NO: 74 to SEQ. NO: 146. An isolated nucleic acid that encodes a H. pylori polypeptide, comprising a nucleotide sequence at least about 60% homologous to a nucleotide sequence selected from the group consisting of SEQ. NO: 1 to SEQ. No. 73, or a complement thereof. The isolated nucleic acid of claim 1, comprising a nucleotide sequence selected from the group consisting of SEQ. NO: 1 to SEQ. No. 73, or a complement thereof. An isolated nucleic acid molecule encoding a H. pylori polypeptide comprising a nucleotide sequence that hybridizes under stringent hybridization conditions to a nucleic acid molecule comprising a nucleotide sequence selected from the group consisting of SEQ. NO: 1 to SEQ. No. 73, or a complement thereof. 6. An isolated nucleic acid comprising a nucleotide sequence of at least 8 nucleotides in length which hybridizes under stringent hybridization conditions to a nucleic acid of which the nucleotide sequence is selected from the group consisting of SEQ. NO: 1 to SEQ. No. 73, or a complement thereof. An isolated nucleic acid comprising a nucleotide sequence encoding a H. pylori cell envelope polypeptide or fragment thereof, which is selected from the group consisting of SEQ. NO: 3, SEQ. NO: 25, SEQ. NO: 48, SEQ. NO: 16, SEQ. No .; 10, SEQ. NO: 45, SEQ. NO: 35, SEQ. No .; 37, SEQ. 0: 7, 251 SEQ. NO: 39, SEQ. NO: 55, SEQ. NO: 18, SEQ. NO: 19, SEQ. NO: 28, SEQ. NO: 30, SEQ. NO: 52, SEQ. NO: 54, SEQ. NO: 56, SEQ. NO: 58, SEQ. NO: 1, SEQ. NO: 42, SEQ. NO: 14, SEQ. NO: 43, SEQ. NO: 11, SEQ. NO: 71, SEQ. NO: 17, SEQ. NO: 57, SEQ. NO: 5, SEQ. NO: 6, SEQ. NO: 8, and SEQ. No. 21, or a complement thereof. The isolated nucleic acid of claim 7, wherein 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. NO: 3, SEQ. NO: 25, and SEQ. No. 48, or a complement thereof. The isolated nucleic acid of claim 7, 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 selected from the group consisting of SEQ. NO: 16, SEQ. NO: 10, SEQ. NO: 45, SEQ. NO: 35, SEQ. NO: 37, SEQ. NO: 7, SEQ. NO: 39, SEQ. NO: 55, SEQ. NO: 18, SEQ. NO: 19, SEQ. NO: 28, SEQ. NO: 30, SEQ. NO: 52, SEQ. NO: 54, SEQ. NO: 56, SEQ. NO: 58, SEQ. NO: 1, SEQ. NO: 42, SEQ. NO: 14, SEQ. NO: 43, SEQ. No. 11, and SEQ. No. 71, or a complement thereof. The isolated nucleic acid of claim 9 wherein the H. pylori outer membrane polypeptide or fragment thereof is H. pylori polypeptide having a phenylalanine residue and a C-terminal tyrosine cluster, or a fragment thereof, encoded by a nucleic acid selected from the group consisting of SEQ. . NO: 1, SEQ. NO: 42, SEQ. NO: 14, SEQ. NO: 43, SEQ. NO: 11 and SEQ. No. 71, or a complement thereof. The isolated nucleic acid of claim 9, wherein the H. pylori outer membrane polypeptide or fragment thereof is H. pylori polypeptide having a terminal phenylalanine residue, or a fragment thereof, encoded by a nucleic acid selected from the group consisting of SEQ. NO: 16, SEQ. NO: 45, SEQ. NO: 35, SEQ. NO: 37, SEQ. NO: 7, SEQ. NO: 39, SEQ. NO: 55, SEQ. NO: 18, 252 SEQ. NO: 19, SEQ. NO: 28, SEQ. NO: 30, SEQ. NO: 52, SEQ. NO: 54, SEQ. NO: 56, SEQ. No. 58, or a complement thereof. An isolated nucleic acid comprising a nucleotide sequence encoding a H. pylori cell envelope polypeptide or fragment thereof, which is selected from the group consisting of SEQ. NO: 76, SEQ. NO. NO: 121, SEQ. NO: 89, SEQ. NO: 83, SEQ. NO: 118, SEQ. NO: 108, SEQ. NO: 110, SEQ. NO: 80, SEQ. NO: 112, SEQ. NO: 128, SEQ. NO: 91, SEQ. NO: 92, SEQ. NO: 101, SEQ. NO: 103, SEQ. NO: 125, SEQ. NO: 127, SEQ. NO: 129, SEQ. NO: 131, SEQ. NO: 74, SEQ. NO: 115, SEQ. NO: 87, SEQ. NO: 116, SEQ. NO: 84, SEQ. NO: 144, SEQ. NO: 90, SEQ. NO: 130, SEQ. NO: 78, SEQ. NO: 79, SEQ. NO: 81, and SEQ. NO: 94. The isolated nucleic acid of claim 12, wherein the H. pylori cell envelope polypeptide or fragment thereof is an H. pylori inner membrane polypeptide or fragment thereof, selected from the group consisting of SEQ. NO: 76, SEQ. NO: 98, and SEQ. NO: 121. The isolated nucleic acid of claim 12, wherein 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. NO: 89, SEQ. NO: 83, SEQ. NO: 118, SEQ. NO: 108, SEQ. NO: 110, SEQ. NO: 80, SEQ. NO: 112, SEQ. NO: 128, SEQ. NO: 91, SEQ. NO: 92, SEQ. NO: 101, SEQ. NO: 103, SEQ. NO: 125, SEQ. NO: 127, SEQ. NO: 129, SEQ. NO: 131, SEQ. NO: 74, SEQ. NO: 115, SEQ. NO: 87, SEQ. NO: 116, SEQ. NO: 84, SEQ. NO: 144, SEQ. NO: 90, and SEQ. NO: 130. The isolated nucleic acid of claim 14, wherein the H. pylori outer membrane polypeptide or fragment thereof is H. pylori polypeptide having terminal phenylalanine residues and a C-terminal tyrosine cluster, or fragment thereof, selected from the group consisting of SEQ. NO: 74, SEQ. NO: 115, SEQ. NO: 87, SEQ. NO: 116, and SEQ. NO: 84 and SEQ. No. 144. 253 The isolated nucleic acid of claim 14, wherein the H. pylori outer membrane polypeptide or fragment thereof is H. pylori polypeptide having terminal phenylalanine residues or a fragment thereof, selected from the group consisting of SEQ. NO: 89, SEQ. NO: 118, SEQ. NO: 108, SEQ. NO: 110, SEQ. NO: 80, SEQ. No .; 112, SEQ. No. 128, SEQ. NO: 91, SEQ. NO: 92, SEQ. NO: 101, SEQ. NO: 103, SEQ. NO: 125, SEQ. NO: 127, SEQ. NO: 129, and SEQ. NO: 131. An isolated nucleic acid comprising a nucleotide sequence encoding a H. pylori secretory polypeptide or fragment thereof, which is selected from the group consisting of SEQ. No .; 72, SEQ. NO: 32. SEQ. No .; 51, SEQ. NO: 2, SEQ. NO: 4, SEQ. NO: 9, SEQ. NO: 13, SEQ. NO: 22, SEQ. NO: 29, SEQ. NO: 31, SEQ. NO: 33, SEQ. NO: 34, SEQ. NO: 36, SEQ. NO: 38, SEQ. NO: 40, SEQ. No .; 41, SEQ. No .; 44, SEQ. No .; 46. SEQ. No .; 49, SEQ. No .; 53. NO: 59, SEQ. NO: 61, SEQ. NO: 62, SEQ. NO: 63, SEQ. NO: 65, SEQ. NO: 66, SEQ. NO: 67, and SEQ. No. 68, or a complement thereof. 18. An isolated nucleic acid comprising a nucleotide sequence encoding H. a pylori secretory polypeptide or fragment thereof, which is selected from the group consisting of SEQ. NO: 145, SEQ. NO: 105, SEQ. NO: 124, SEQ. NO: 75, SEQ. NO: 77, SEQ. NO: 82, SEQ. NO. 86. SEQ. NO: 95, SEQ. No .: 102, SEQ. NO: 104, SEQ. No .; 106, SEQ. NO: 107, SEQ. NO: 109, SEQ. No .: 111, SEQ. NO: 113, SEQ. NO: 114, SEQ. NO: 117, SEQ. No .; 119, SEQ. No .: 122, SEQ. NO: 126, SEQ. NO: 132, SEQ. NO: 134, SEQ. NO: 135, SEQ. No .: 136, SEQ. NO: 138, SEQ. NO: 139, SEQ. No. 140, and SEQ. NO: 141. 19. An isolated nucleic acid comprising a nucleotide sequence encoding a H. pylori cell polypeptide or fragment thereof, which is selected from the group consisting of SEQ. NO: 12, SEQ. NO: 15, SEQ. NO: 20, SEQ. NO: 23, SEQ. NO: 24, SEQ. NO: 26, SEQ. NO: 27. SEQ. NO: 47, SEQ. NO: 50, SEQ. NO: 60, SEQ. NO: 64, SEQ. NO: 69, SEQ. No. 70, and SEQ. No. 73, or a complement thereof. 254 An isolated nucleic acid comprising a nucleotide sequence encoding a H. pylori cell polypeptide or fragment thereof, which is selected from the group consisting of SEQ. NO. 85. SEQ. NO: 88, SEQ. NO: 93, SEQ. NO: 96, SEQ. NO: 97, SEQ. NO: 99, SEQ. NO: 100, SEQ. NO: 120, SEQ. NO: 123, SEQ. NO: 133, SEQ. NO: 137, SEQ. NO: 142, SEQ. NO: 143, and SEQ. NO: 146. 21. A probe comprising a nucleotide sequence consisting of at least 8 nucleotides of a nucleotide sequence selected from the group consisting of SEQ. NO: 1 to SEQ. No. 73, or a complement thereof. A recombinant expression vector comprising the nucleic acid of any one of claims 1, 2, 3, 4, 5, 6, 7, 12, 17, 18, 19 or 20, which is operably linked to a transcriptional regulatory element. 23. A cell comprising the recombinant expression vector of claim 22. 24. A method for producing a H. pylori polypeptide, comprising culturing the cells of claim 23 under conditions that allow expression of the polypeptide. 25. The method of claim 24, further comprising purifying the polypeptide from the cell. A method for detecting the presence of a Helicobacter nucleic acid in a sample, comprising (a) contacting the sample with a nucleic acid of any one of claims 6 or 21 so as to form a hybrid 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 Helicobacter nucleic acid in the sample. An isolated H. pylori polypeptide comprising an amino acid sequence that is at least about 60% homologous to H. pylori polypeptide selected from the group consisting of SEQ. NO: 74 to SEQ. NO: 146. 28. An isolated H. pylori polypeptide that is encoded by a nucleic acid comprising a nucleotide sequence that is at least about 60% 255 homologous to a nucleotide sequence selected from the group consisting of SEQ. NO: 1 to SEQ. NO: 73. The isolated H. pylori polypeptide of claim 28, which is encoded by a nucleotide sequence selected from the group consisting of SEQ. NO: 1 to SEQ. NO .: 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. NO: 1 to SEQ. No. 73, or a complement thereof. An isolated H. pylori polypeptide comprising an amino acid sequence selected from the group consisting of SEQ. NO: 74 to SEQ. NO: 146. An isolated H. pylori cell or envelope polypeptide, or fragment thereof, which is selected from the group consisting of SEQ. NO: 76, SEQ. NO: 98, SEQ. NO: 121, SEQ. NO: 89, SEQ. NO: 83, SEQ. NO: 118, SEQ. NO: 108, SEQ. NO: 110, SEQ. NO: 80, SEQ. NO: 112, SEQ. NO: 128, SEQ. NO: 91, SEQ. NO: 92, SEQ. NO: 101, SEQ. NO: 103, SEQ. NO: 125, SEQ. NO: 127, SEQ. NO: 129, SEQ. NO: 131, SEQ. NO: 74, SEQ. NO: 115, SEQ. NO: 87, SEQ. NO: 116, SEQ. NO: 84, SEQ. NO: 144, SEQ. NO: 90, SEQ. NO: 130, SEQ. NO: 78, SEQ. NO: 79, SEQ. NO: 81, and SEQ. NO: 94. The isolated polypeptide of claim 32, wherein the H. pylori cell envelope polypeptide or fragment thereof is an H. pylori inner membrane polypeptide or fragment thereof, selected from the group consisting of SEQ. NO: 76, SEQ. NO: 98, and SEQ. NO: 121. The isolated polypeptide of claim 32, wherein 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. NO: 89, SEQ. NO: 83, SEQ. NO: 118, SEQ. NO: 108, SEQ. NO: 110, SEQ. NO: 80, SEQ. NO: 112, SEQ. NO: 128, SEQ. NO: 91, SEQ. NO: 92, SEQ. NO: 101, SEQ. NO: 103, SEQ. NO: 125, SEQ. NO: 127, SEQ. NO: 129, SEQ. NO: 131, SEQ. No .: 74, 256 SEQ. NO: 115, SEQ. NO: 87, SEQ. NO: 116, SEQ. NO: 84, SEQ. NO: 144, SEQ. NO: 90, and SEQ. NO: 130. The isolated polypeptide of claim 34, wherein the H. pylori outer membrane polypeptide or fragment thereof is an H. pylori polypeptide having a terminal phenyphalanine residue and a C-terminal tyrosine cluster or fragment thereof, selected from the group consisting of SEQ. No .; 74, SEQ. NO: 115, SEQ. No .; 87, SEQ. NO: 116, SEQ. NO: 84 and SEQ. No. 144. The isolated polypeptide of claim 34, wherein the H. pylori outer membrane polypeptide or fragment thereof is H. pylori polypeptide having a terminal phenylalanine residue or fragment thereof, selected from the group consisting of SEQ. No .; 89, SEQ. NO: 118, SEQ. No .; 108, SEQ. NO: 110, SEQ. No .; 80, SEQ. NO: 112, SEQ. NO: 128, SEQ. NO: 91, SEQ. NO: 92, SEQ. NO: 101, SEQ. NO: 103, SEQ. NO: 125, SEQ. NO: 127, SEQ. NO: 129, and SEQ. NO: 131. 37. An isolated H. pylori cell envelope polypeptide or fragment thereof that is encoded by a nucleic acid selected from the group consisting of SEQ. NO: 3, SEQ. NO: 25, SEQ. NO: 48, SEQ. NO: 16, SEQ. NO: 10, SEQ. NO: 45, SEQ. NO: 35, SEQ. NO: 37, SEQ. NO: 7, SEQ. NO: 39, SEQ. No .; 55, SEQ. NO: 18, SEQ. NO: 19, SEQ. NO: 28, SEQ. NO: 30, SEQ. NO: 52, SEQ. No .: 54, SEQ. NO: 56, SEQ. NO: 58, SEQ. NO: 1, SEQ. NO: 42, SEQ. NO: 14, SEQ. NO: 43, SEQ. NO: 11, SEQ. NO: 71, SEQ. NO: 17, SEQ. NO: 57, SEQ. NO: 5, SEQ. NO: 6, SEQ. NO: 8, and SEQ. NO: 21. The isolated polypeptide of claim 37, wherein the H. pylori cell envelope polypeptide or fragment thereof is an H. pylori inner membrane polypeptide or fragment thereof that is encoded by a nucleic acid selected from the group consisting of SEQ. NO: 3, SEQ. NO: 25, and SEQ. NO: 48. The isolated polypeptide of claim 37, wherein the H. pylori cell envelope polypeptide or fragment thereof is an H. pylori outer membrane polypeptide or fragment thereof that is encoded by a nucleic acid selected from the group consisting of SEQ. NO: 16, SEQ. No .; 10, SEQ. NO: 45, SEQ. No: 35, 257 SEQ. NO: 37, SEQ. NO: 7, SEQ. NO: 39, SEQ. NO: 55, SEQ. NO: 18, SEQ. NO: 19, SEQ. NO: 28, SEQ. NO: 30, SEQ. NO: 52, SEQ. NO: 54, SEQ. NO: 56, SEQ. NO: 58, SEQ. NO: 1, SEQ. NO: 42, SEQ. NO: 14, SEQ. NO: 43, SEQ. No. 11, and SEQ. NO: 71. The isolated polypeptide of claim 39, wherein the H. pylori outer membrane polypeptide or fragment thereof is H. pylori polypeptide having a terminal phenylalanine residue and a C-terminal tyrosine cluster, or a fragment thereof that is encoded by a nucleic acid selected from the group consisting of SEQ. NO: 1, SEQ. NO: 42, SEQ. NO: 14, SEQ. NO: 43, SEQ. NO: 11 and SEQ. No. 71. The isolated polypeptide of claim 39, wherein the H. pylori outer membrane polypeptide or fragment thereof is H. pylori polypeptide having a terminal phenylalanine residue, or a fragment thereof that is encoded by a nucleic acid selected from the group consisting of SEQ. NO: 16, SEQ. NO: 45, SEQ. NO: 35, SEQ. NO: 37, SEQ. NO: 7, SEQ. NO: 39, SEQ. NO: 55, SEQ. NO: 18, SEQ. NO: 19, SEQ. NO: 28, SEQ. NO: 30, SEQ. NO: 52, SEQ. NO: 54, SEQ. NO: 56, SEQ. NO: 58. 42. An isolated H. pylori cell polypeptide, or fragment thereof, which is selected from the group consisting of SEQ. NO: 85, SEQ. NO: 88, SEQ. NO: 93, SEQ. NO: 96, SEQ. NO: 97, SEQ. NO: 99, SEQ. No .; 100, SEQ. No .; 120, SEQ. No .; 123, SEQ. NO: 133, SEQ. NO: 137, SEQ. NO: 142, SEQ. NO: 143, and SEQ. NO: 146. 43. An isolated H. pylori cell polypeptide or fragment thereof that is encoded by a nucleic acid selected from the group consisting of SEQ. NO: 12, SEQ. NO: 15, SEQ. NO: 20, SEQ. NO: 23, SEQ. NO: 24, SEQ. NO: 26, SEQ. NO: 27, SEQ. NO: 47, SEQ. NO: 50, SEQ. NO: 60, SEQ. NO: 64, SEQ. NO: 69, SEQ. No .; 70, and SEQ. NO: 73. 44. An isolated H. pylori secretory polypeptide or fragment thereof, which is selected from the group consisting of SEQ. NO: 145, SEQ. NO: 105, SEQ. No .: 124, 258 SEQ. NO: 75, SEQ. NO: 77, SEQ. NO: 82, SEQ. NO: 86, SEQ. NO: 95, SEQ. NO: 102, SEQ. NO: 104, SEQ. NO: 106, SEQ. NO: 107, SEQ. NO: 109, SEQ. NO: 111, SEQ. NO: 113, SEQ. NO: 114, SEQ. NO: 117, SEQ. NO: 119, SEQ. NO: 122, SEQ. NO: 126, SEQ. NO: 132, SEQ. NO: 134, SEQ. NO: 135, SEQ. NO: 136, SEQ. NO: 138, SEQ. NO: 139, SEQ. No. 140, and SEQ. NO: 141. 45. An isolated H. pylori secretion polypeptide or fragment thereof that is encoded by a nucleic acid selected from the group consisting of SEQ. NO: 72, SEQ. NO: 32, SEQ. NO: 51, SEQ. NO: 2, SEQ. NO: 4, SEQ. NO: 9, SEQ. NO: 13, SEQ. NO: 22, SEQ. NO: 29, SEQ. NO: 31. SEQ. NO: 33, SEQ. NO: 34, SEQ. NO: 36, SEQ. NO: 38, SEQ. NO: 40, SEQ. NO: 41, SEQ. NO: 44, SEQ. NO: 46, SEQ. NO: 49, SEQ. NO: 53, SEQ. NO: 59, SEQ. NO: 61, SEQ. NO: 62, SEQ. NO: 63, SEQ. NO. NO: 66, SEQ. NO: 67, and SEQ. NO: 68. 46. A fusion protein comprising an H. pylori polypeptide comprising an amino acid sequence selected from the group consisting of SEQ. No .; 74 to SEQ. No. 146, operably linked to non-H. pylori polypeptide. A vaccine composition for the prophylaxis or treatment of a H. pylori infection, comprising an effective amount of at least one isolated nucleic acid according to any one of claims 1, 2, 3, 4, 5, 6, 7,12,17,18, 19 or 20. A vaccine composition for the prophylaxis or treatment of a H. pylori infection, comprising an effective amount of at least one H. pylori polypeptide or fragment thereof according to any one of claims 26, 27, 28, 29, 30, 31, 32, 37; 42, 43.44 or 45. 49. The vaccine composition of claim 47, further comprising a pharmaceutically acceptable carrier. 50. The vaccine composition of claim 48, further comprising a pharmaceutically acceptable carrier. 51. The vaccine composition of claim 49, wherein the pharmaceutically acceptable carrier comprises an adjuvant. 259 52. The vaccine composition of claim 50, wherein the pharmaceutically acceptable carrier comprises an adjuvant. 53. The vaccine composition of claim 49, wherein the pharmaceutically acceptable carrier comprises a delivery system. 54. The vaccine composition of claim 50, wherein the pharmaceutically acceptable carrier comprises a delivery system. 55. The vaccine composition of claim 53, wherein the delivery system comprises a live vector. 56. The vaccine composition of claim 54, wherein the delivery system comprises a live vector. 57. The vaccine composition of claim 55, wherein the living vector is a bacterium or a virus. 58. The vaccine composition of claim 56, wherein the living vector is a bacterium or a virus. 59. The vaccine composition of claim 53, wherein the pharmaceutically acceptable carrier further comprises an adjuvant. 60. The vaccine composition of claim 54, wherein the pharmaceutically acceptable carrier further comprises an adjuvant. 61. 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 claim 47, such that treating or reducing the risk of H. pylori infection. 62. 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 claim 48, such that treating or reducing the risk of H. pylori infection. 63. A method of making a vaccine composition comprising combining at least one isolated H. pylori polypeptide or a polypeptide thereof. 260 of a fragment selected from the group consisting of SEQ. NO: 74 to SEQ. No. 146 with a pharmaceutically acceptable carrier to form a vaccine formulation. 64. A method of making a vaccine composition comprising (a) providing at least one isolated H. pylori polypeptide or fragment thereof selected from the group consisting of SEQ. NO: 74 to SEQ. NO: 146; and (b) combining at least one isolated H. pylori polypeptide or fragment thereof with a pharmaceutically acceptable carrier to form a vaccine preparation. 65. A method of making a vaccine composition, comprising (a) culturing the cells under conditions that allow expression of a H. pylori polypeptide or fragment thereof selected from the group consisting of SEQ. NO: 74 to SEQ. NO: 146; (b) isolating the H. pylori polypeptide from the cell; and (c) combining at least one isolated H. pylori polypeptide or fragment thereof with a pharmaceutically acceptable carrier to form a vaccine composition.