AU739641B2

AU739641B2 - Nucleic acid and amino acid sequences relating to helicobacter pylori and vaccine compositions thereof

Info

Publication number: AU739641B2
Application number: AU58954/98A
Authority: AU
Inventors: Richard A. Alm; Lillian Marie Castriotta; Peter C. Doig; Zita Kabok; Douglas Smith
Original assignee: Astra AB
Current assignee: AstraZeneca AB
Priority date: 1996-12-05
Filing date: 1997-12-05
Publication date: 2001-10-18
Anticipated expiration: 2017-12-05
Also published as: IS5047A; PL333943A1; NZ335633A; AU5895498A; ID21946A; JP2001510992A; EP0964699A1; BR9714133A; IL129746A0; AR010337A1; KR20000069297A; WO1998024475A1; SK57999A3; EE9900226A; NO992158D0; TR199901262T2; NO992158L; CA2273199A1; CN1246799A; EP0964699A4

Description

WO 98/24475 PCT/US97/22104 -1- NUCLEIC ACID AND AMINO ACID SEQUENCES RELATING TO HELICOBACTER PYLORI AND VACCINE COMPOSITIONS THEREOF Background of the Invention Helicobacterpylori is a gram-negative, S-shaped, microaerophilic bacterium that was discovered and cultured from a human gastric biopsy specimen. (Warren, J.R. and B. Marshall, (1983) Lancet 1: 1273-1275; and Marshall et al., (1984) Microbios Lett. 83-88). H. pylori has been strongly linked to chronic gastritis and duodenal ulcer disease. (Rathbone et. al., (1986) Gut 27: 635-641). Moreover, evidence is accumulating for an etiologic role of H. pylori in nonulcer dyspepsia, gastric ulcer disease, and gastric adenocarcinoma. (Blaser M. (1993) Trends Microbiol. 1: 255- 260). Transmission of the bacteria 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 human gastric mucosa, establishing an infection that usually persists for decades. Infection by H. pylori is prevalent worldwide. Developed countries have infection rates over 50% of the adult population, while developing countries have infection rates reaching 90% of the adults over the age of 20. (Hopkins R. J. and J. G. Morris (1994) Am. J. Med. 97: 265-277).

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

Acad. Sci. USA 90: 2035-203).

Numerous therapeutic agents are currently available that eradicate H. pylori infections in vitro. (Huesca et. al., (1993) Zbl. Bakt. 280: 244-252; Hopkins, R. J. and J.

G. Morris, supra). However, many of these treatments are suboptimally effective in vivo because of bacterial resistance, altered drug distribution, patient non-compliance or poor drug availabilty. (Hopkins, R. J. and J. G. Morris, supra). Treatment with antibiotics combined with bismuth are part of the standard regime used to-treat H pylori infection.

WO 98/24475 PCTIS97t22104 -2- (Malfertheiner, P. and J. E. Dominguez-Munoz (1993) Clinical Therapeutics 15 Supp.

B: 37-48). Recently, combinations of a proton pump inhibitors and a single antibiotic have been shown to ameliorate duodenal ulcer disease. (Malfertheiner, P. and J. E.

Dominguez-Munoz supra). However, methods employing antibiotic agents can have the problem of the emergence of bacterial strains which are resistant to these agents.

(Hopkins, R. J. and J. G. Morris, supra). These limitations demonstrate that new more effective methods are needed to combat H. pylori infections in vivo. In particular, the design of new vaccines that may prevent infection by this bacterium is highly desirable.

Summary of the Invention This invention relates to novel genes, genes encoding polypeptides such as bacterial surface proteins, from the organism Helicobacterpylori (H pylori), and other related genes, their products, and uses thereof. The nucleic acids and peptides of the present invention have utility for diagnostic and therapeutics for H. pylori and other Helicobacter species. They can also be used to detect the presence of H. pylori and other Helicobacter species in a sample; and for use in screening compounds for the ability to interfere with the H. pylori life cycle or to inhibit H. pylori infection. More specifically, this invention features compositions of nucleic acids corresponding to entire coding sequences of H pylori proteins, including surface or secreted proteins or parts 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 and recombinant DNA techniques. This invention also features antibodies and nucleic acids useful as probes to detect H. pylori infection. In addition, vaccine compositions and methods for the protection or treatment of infection by H.

pylori are within the scope of this invention.

25 Detailed Description of the Drawings Figure 1 depicts an amino acid sequence alignment of five H. pylori proteins i. (depicted in the single letter amino acid code and designated by their amino acid Sequence ID Numbers; shown N-terminal to C-terminal, left to right).

Figure 2 depicts the N-terminal portion of three H pylori proteins (depicted in 0 30 the single letter amino acid code and designated by their amino acid Sequence ID Numbers; shown N-terminal to C-terminal, left to right).

Microorganism Deposit oAs indicated below in the present specification, as well as in the PCT Request form lodged in support of International Patent Application No. PCT/US97/22104, a strain of H-pylori was deposited under ATCC 55679, the letters ATCC in that accession or jRAQ registration number indicating that the depositary for that deposit is American Type Culture Collection of 12301 Parklawn Drive, Rockville, MD 20852, United States of i, America, in those letters being the well known abbreviation for that depositary.

WO 98/24475 PCT/US97/22104 -3- Detailed Description of the Invention In one aspect, the invention features a recombinant or substantially pure preparation ofH. pylori polypeptide of SEQ ID NO: 98. The invention also includes substantially pure nucleic acid encoding an H. pylori polypeptide of SEQ ID NO: 98, such nucleic acid is contained in SEQ ID NO: 1. The H. pylori polypeptide sequences of the invention described herein are contained in the Sequence Listing, and the nucleic acids encoding H pylori polypeptides of the invention are contained in the Sequence Listing.

In another aspect, the invention features a substantially pure nucleic acid encoding an H pylori polypeptide having an amino acid sequence of SEQ ID NO: 99, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: 2.

In another aspect, the invention features a substantially pure nucleic acid encoding an H. pylori polypeptide having an amino acid sequence of SEQ ID NO: 100, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: 3.

In another aspect, the invention features a substantially pure nucleic acid encoding an H. pylori polypeptide having an amino acid sequence of SEQ ID NO: 101, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: 4.

In another aspect, the invention features a substantially pure nucleic acid encoding an H. pylori polypeptide having an amino acid sequence of SEQ ID NO: 102, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: In another aspect, the invention features a substantially pure nucleic acid encoding an H. pylori polypeptide having an amino acid sequence of SEQ ID NO: 103, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: 6.

In another aspect, the invention features a substantially pure nucleic acid encoding an H pylori polypeptide having an amino acid sequence of SEQ ID TO: 104, -A.J&Ar 1"t j J. I VW.J', LL 11U ll V a LIIIII u al 3l, II.,I UI 3JLiu v I U. 1U I Vsuch as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: 7.

In another aspect, the invention features a substantially pure nucleic acid encoding an H. pylori polypeptide having an amino acid sequence of SEQ ID NO: 105, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: 8.

In another aspect, the invention features a substantially pure nucleic acid encoding an H. pylori polypeptide havin- a-i amino acid sequence of SEQ ID NO: 106, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: 9.

In another aspect, the invention features a substantially pure nucleic acid encoding an H. pylori polypeptide having an amino acid sequence of SEQ ID NO: 107, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: WO 98/24475 PCT/US97/22104 -4- In another aspect, the invention features a substantially pure nucleic acid encoding an H. pylori polypeptide having an amino acid sequence of SEQ ID NO: 108, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: 11.

In another aspect, the invention features a substantially pure nucleic acid encoding an H. pylori polypeptide having an amino acid sequence of SEQ ID NO: 109, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: 12.

In another aspect, the invention features a substantially pure nucleic acid encoding an H pylori polypeptide having an amino acid sequence of SEQ ID NO: 110, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: 13.

In another aspect, the invention features a substantially pure nucleic acid encoding an H pylori polypeptide having an amino acid sequence of SEQ ID NO: 111, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: 14.

In another aspect, the invention features a substantially pure nucleic acid encoding an H. pylori polypeptide having an amino acid sequence of SEQ ID NO: 112, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: In another aspect, the invention features a substantially pure nucleic acid encoding an H. pylori polypeptide having an amino acid sequence of SEQ ID NO: 113, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: 16.

In another aspect, the invention features a substantially pure nucleic acid encoding an H pylori polypeptide having an amino acid sequence of SEQ ID NO: 114, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: 17.

In another aspect, the invention features a substantially pure nucleic acid encoding an H pylori polypeptide having an amino acid sequence of SEQ ID NO: 115, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: 18.

In another aspect, the invention features a substantially pure nucleic acid encoding an H. pylori polypeptide having an amino acid sequence of SEQ ID NO: 116, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: 19.

In another aspect, the invention features a substantially pure nucleic acid encoding an H. pylori polypeptide having an amino acid sequence of SEQ ID NO: 117, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: In anther aspect, the invention features a substantially pure nucleic acid encoding an H. pylori polypeptide having an amino acid sequence of SEQ ID NO: 118, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: 21.

In another aspect, the invention features a substantially pure nucleic acid encoding an H. pylori polypeptide having an amino acid sequence of SEQ ID NO: 119, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: 22.

WO 98/24475 PCT/US97/22104 In another aspect, the invention features a substantially pure nucleic acid encoding an H. pylori polypeptide having an amino acid sequence of SEQ ID NO: 120, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: 23.

In another aspect, the invention features a substantially pure nucleic acid encoding an H. pylori polypeptide having an amino acid sequence of SEQ ID NO: 121, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: 24.

In another aspect, the invention features a substantially pure nucleic acid encoding an H. pylori polypeptide having an amino acid sequence of SEQ ID NO: 122, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: In another aspect, the invention features a substantially pure nucleic acid encoding an H pylori polypeptide having an amino acid sequence of SEQ ID NO: 123, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: 26.

In another aspect, the invention features a substantially pure nucleic acid encoding an H. pylori polypeptide having an amino acid sequence of SEQ ID NO: 124, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: 27.

In another aspect, the invention features a substantially pure nucleic acid encoding an H. pylori polypeptide having an amino acid sequence of SEQ ID NO: 125, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: 28.

In another aspect, the invention features a substantially pure nucleic acid encoding an H. pylori polypeptide having an amino acid sequence of SEQ ID NO: 126, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: 29.

In another aspect, the invention features a substantially pure nucleic acid encoding an H. pylori polypeptide having an amino acid sequence of SEQ ID NO: 127, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: In anothr aspect, the invention features a substantially pure nucleic acid encoding an H. pylori polypeptide having an amino acid sequence of SEQ ID NO: 128, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: 31.

In another aspect, the invention features a substantially pure nucleic acid encoding an H. pylori polypeptide having an amino acid sequence of SEQ ID NO: 129, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: 32.

In another aspect, the invention features a substantially pure nucleic acid encoding an H. pylori polypeptide having an amino acid sequence of SEQ ID NO: 130, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: 33.

In another aspect, the invention features a substantially pure nucleic acid encoding an H. pylori polypeptide having an amino acid sequence of SEQ ID NO: 131, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: 34.

WO 98/24475 PCT/US97/22104 -6- In another aspect, the invention features a substantially pure nucleic acid encoding an H pylori polypeptide having an amino acid sequence of SEQ ID NO: 132, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: In another aspect, the invention features a substantially pure nucleic acid encoding an H. pylori polypeptide having an amino acid sequence of SEQ ID NO: 133, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: 36.

In another aspect, the invention features a substantially pure nucleic acid encoding an H pylori polypeptide having an amino acid sequence of SEQ ID NO: 134, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: 37.

In another aspect, the invention features a substantially pure nucleic acid encoding an H pylori polypeptide having an amino acid sequence of SEQ ID NO: 135, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: 38.

In another aspect, the invention features a substantially pure nucleic acid encoding an H. pylori polypeptide having an amino acid sequence of SEQ ID NO: 136, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: 39.

In another aspect, the invention features a substantially pure nucleic acid encoding an H pylori polypeptide having an amino acid sequence of SEQ ID NO: 137, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: In another aspect, the invention features a substantially pure nucleic acid encoding an H pylori polypeptide having an amino acid sequence of SEQ ID NO: 138, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: 41.

In another aspect, the invention features a substantially pure nucleic acid encoding an H. pylori polypeptide having an amino acid sequence of SEQ ID NO: 139, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: 42.

n another aspect, the invention f+eatures a substantially pure nucleic acid 111 JILII L.LJ.i .I II IL LVIAJI L%,LL1 U JUaCL 4LJ-ILUIY I l encoding an H. pylori polypeptide having an amino acid sequence of SEQ ID NO: 140, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO:43.

In another aspect, the invention features a substantially pure nucleic acid encoding an H pylori polypeptide having an amino acid sequence of SEQ ID NO: 141, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: 44.

In another aspect, the invention features a substantially pr re nucleic acid encoding an H. pylori polypeptide having an amino acid sequence of SEQ ID NO: 142, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: In another aspect, the invention features a substantially pure nucleic acid encoding an H. pylori polypeptide having an amino acid sequence of SEQ ID NO: 143, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: 46.

WO 98/24475 PCT/US97/22104 -7- In another aspect, the invention features a substantially pure nucleic acid encoding an H. pylori polypeptide having an amino acid sequence of SEQ ID NO: 144, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: 47.

In another aspect, the invention features a substantially pure nucleic acid encoding an H. pylori polypeptide having an amino acid sequence of SEQ ID NO: 145, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: 48.

In another aspect, the invention features a substantially pure nucleic acid encoding an H. pylori polypeptide having an amino acid sequence of SEQ ID NO: 146, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: 49.

In another aspect, the invention features a substantially pure nucleic acid encoding an H. pylori polypeptide having an amino acid sequence of SEQ ID NO: 147, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: In another aspect, the invention features a substantially pure nucleic acid encoding an H. pylori polypeptide having an amino acid sequence of SEQ ID NO: 148, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: 51.

In another aspect, the invention features a substantially pure nucleic acid encoding an H. pylori polypeptide having an amino acid sequence of SEQ ID NO: 149, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: 52.

In another aspect, the invention features a substantially pure nucleic acid encoding an H. pylori polypeptide having an amino acid sequence of SEQ ID NO: 150, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: 53.

In another aspect, the invention features a substantially pure nucleic acid encoding an H. pylori polypeptide having an amino acid sequence of SEQ ID NO: 151, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: 54.

In another aspect, the invention Ifeatures a substantially pure nucleic acid encoding an H. pylori polypeptide having an amino acid sequence of SEQ ID NO: 152, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: In another aspect, the invention features a substantially pure nucleic acid encoding an H. pylori polypeptide having an amino acid sequence of SEQ ID NO: 153, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: 56.

In another aspect, the irve',tion features a substantially pure nucleic acid encoding an H. pylori polypeptide having an amino acid sequence of SEQ ID NO: 154, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: 57.

In another aspect, the invention features a substantially pure nucleic acid encoding an H. pylori polypeptide having an amino acid sequence of SEQ ID NO: 155, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: 58.

WO 98/24475 PCTIUS97/22104 -8- In another aspect, the invention features a substantially pure nucleic acid encoding an H. pylori polypeptide having an amino acid sequence of SEQ ID NO: 156, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: 59.

In another aspect, the invention features a substantially pure nucleic acid encoding an H. pylori polypeptide having an amino acid sequence of SEQ ID NO: 157, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: In another aspect, the invention features a substantially pure nucleic acid encoding an H. pylori polypeptide having an amino acid sequence of SEQ ID NO: 158, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: 61.

In another aspect, the invention features a substantially pure nucleic acid encoding an H. pylori polypeptide having an amino acid sequence of SEQ ID NO: 159, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: 62.

In another aspect, the invention features a substantially pure nucleic acid encoding an H. pylori polypeptide having an amino acid sequence of SEQ ID NO: 160, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: 63.

In another aspect, the invention features a substantially pure nucleic acid encoding an H. pylori polypeptide having an amino acid sequence of SEQ ID NO: 161, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: 64.

In another aspect, the invention features a substantially pure nucleic acid encoding an H. pylori polypeptide having an amino acid sequence of SEQ ID NO: 162, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: In another aspect, the invention features a substantially pure nucleic acid encoding an H pylori polypeptide having an amino acid sequence of SEQ ID NO: 163, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: 66.

In another aspect, the invention features a substantially pure nucleic acid encoding an H. pylori polypeptide having an amino acid sequence of SEQ ID NO: 164, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: 67.

In another aspect, the invention features a substantially pure nucleic acid encoding an H. pylori polypeptide having an amino acid sequence of SEQ ID NO: 165, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: 68.

In another aspect, the invention features a substantially pure nucleic acid encoding an H. pylori polypeptide having an amino acid sequence of SEQ ID NO: 166, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: 69.

In another aspect, the invention features a substantially pure nucleic acid encoding an H pylori polypeptide having an amino acid sequence of SEQ ID NO: 167, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: WO 98/24475 PCT/US97/22104 -9- In another aspect, the invention features a substantially pure nucleic acid encoding an H. pylori polypeptide having an amino acid sequence of SEQ ID NO: 168, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: 71.

In another aspect, the invention features a substantially pure nucleic acid encoding an H. pylori polypeptide having an amino acid sequence of SEQ ID NO: 169, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: 72.

In another aspect, the invention features a substantially pure nucleic acid encoding an H pylori polypeptide having an amino acid sequence of SEQ ID NO: 170, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: 73.

In another aspect, the invention features a substantially pure nucleic acid encoding an H. pylori polypeptide having an amino acid sequence of SEQ ID NO: 171, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: 74.

In another aspect, the invention features a substantially pure nucleic acid encoding an H pylori polypeptide:having an amino acid sequence of SEQ ID NO: 172, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: In another aspect, the invention features a substantially pure nucleic acid encoding an H pylori polypeptide having an amino acid sequence of SEQ ID NO: 173, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: 76.

In another aspect, the invention features a substantially pure nucleic acid encoding an H. pylori polypeptide having an amino acid sequence of SEQ ID NO: 174, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: 77.

In another aspect, the invention features a substantially pure nucleic acid encoding an H pylori polypeptide having an amino acid sequence of SEQ ID NO: 175, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: 78.

In another aspect, the invention features a substantially pure nucleic acid encoding an H pylori polypeptide having an amino acid sequence of SEQ ID NO: 176, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: 79.

In another aspect, the invention features a substantially pure nucleic acid encoding an H pylori polypeptide having an amino acid sequence of SEQ ID NO: 177, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: In another aspect, the invention features a substantially pure nucleic acid encoding an H pylori polypeptide having an amino acid sequence of SEQ ID NO: 178, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: 81.

In another aspect, the invention features a substantially pure nucleic acid encoding an H pylori polypeptide having an amino acid sequence of SEQ ID NO: 179, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: 82.

WO 98/24475 PCT/US97/22104 In another aspect, the invention features a substantially pure nucleic acid encoding an H pylori polypeptide having an amino acid sequence of SEQ ID NO: 180, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: 83.

In another aspect, the invention features a substantially pure nucleic acid encoding an H. pylori polypeptide having an amino acid sequence of SEQ ID NO: 181, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: 84.

In another aspect, the invention features a substantially pure nucleic acid encoding an H pylori polypeptide having an amino acid sequence of SEQ ID NO: 182, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: In another aspect, the invention features a substantially pure nucleic acid encoding an H. pylori polypeptide having an amino acid sequence of SEQ ID NO: 183, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: 86.

In another aspect, the invention features a substantially pure nucleic acid encoding an H. pylori polypeptide having an amino acid sequence of SEQ ID NO: 184, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: 87.

In another aspect, the invention features a substantially pure nucleic acid encoding an H. pylori polypeptide having an amino acid sequence of SEQ ID NO: 185, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: 88.

In another aspect, the invention features a substantially pure nucleic acid encoding an H pylori polypeptide having an amino acid sequence of SEQ ID NO: 186, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: 89.

In another aspect, the invention features a substantially pure nucleic acid encoding an H. pylori polypeptide having an amino acid sequence of SEQ ID NO: 187, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: In another aspect, the invention features a substantially pure nucleic acid encoding an H. pylori polypeptide having an amino acid sequence of SEQ ID NO: 188, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: 91.

In another aspect, the invention features a substantially pure nucleic acid encoding an H. pylori polypeptide having an amino acid sequence of SEQ ID NO: 189, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: 92.

In another aspect, the invention features a substa itially pure nucleic acid encoding an H. pylori polypeptide having an amino acid sequence of SEQ ID NO: 190, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: 93.

In another aspect, the invention features a substantially pure nucleic acid encoding an H. pylori polypeptide having an amino acid sequence of SEQ ID NO: 191, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: 94.

WO 98/24475 PCT/US97/22104 11- In another aspect, the invention features a substantially pure nucleic acid encoding an H. pylori polypeptide having an amino acid sequence of SEQ ID NO: 192, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: In another aspect, the invention features a substantially pure nucleic acid encoding an H. pylori polypeptide having an amino acid sequence of SEQ ID NO: 193, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: 96.

In another aspect, the invention features a substantially pure nucleic acid encoding an H. pylori polypeptide having an amino acid sequence of SEQ ID NO: 194, such as a nucleic acid comprising a nucleotide sequence of SEQ ID NO: 97.

In another aspect, the invention features an isolated nucleic acid having a nucleotide sequence encoding an H. pylori polypeptide at least about 60% homologous to an amino acid sequence selected from the group consisting of SEQ ID NO: 98-SEQ ID NO: 194. In a preferred embodiment, the isolated nucleic acid includes a nucleotide sequence selected from the group consisting of SEQ ID NO: 1-SEQ ID NO: 97, or a complement thereof.

In another aspect, the invention features an isolated nucleic acid having a nucleotide sequence encoding an H. pylori polypeptide selected from the group consisting of SEQ ID NO: 98-SEQ ID NO: 194.

In another aspect, the invention features an isolated nucleic acid which encodes an H. pylori polypeptide, having a nucleotide sequence at least about 60% homologous to a nucleotide sequence selected from the group consisting of SEQ ID NO: 1-SEQ ID NO: 97, or a complement thereof.

In another aspect, the invention features an isolated nucleic acid molecule encoding an H. pylori polypeptide, having a nucleotide sequence which hybridizes under stringent hybridization conditions to a nucleic acid molecule having the nucleotide sequence selected from the group consisting of SEQ ID NO: 1-SEQ ID NO: 97, or a complement thereof.

In another aspect, the invention features an isolated nucleic acid having a nucleotide sequence of at least 8 nucleotides in length, wherein the sequence hybridizes under stringent hybridization conditions to a nucleic acid having a nucleotide sequence selected from the grou, consisting of SEQ ID NO: 1-SEQ ID NO: 97, or a complement thereof.

Particularly preferred is an isolated nucleic acid having a nucleotide sequence encoding an H pylori cell envelope polypeptide or a fragment thereof, the nucleic acid selected from the group consisting of SEQ ID NO: 63, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 50, SEQ ID NO: 51, SEQ ID NO: 61, WO 98/24475 PCT/US97/22104 -12- SEQ ID NO: 79, SEQ ID NO: 80, SEQ ID NO: 84, SEQ ID NO: 85, SEQ ID NO: 91, SEQ ID NO: 94, SEQ ID NO: 5, SEQ ID NO: 11, SEQ ID NO: 26, SEQ ID NO: 36, SEQ ID NO: 42, SEQ ID NO: 52, SEQ ID NO: 22, SEQ ID NO: 29, SEQ ID NO: SEQ ID NO: 65, SEQ ID NO: 66, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 6, SEQ ID NO: 34, SEQ ID NO: 35, SEQ ID NO: 60, SEQ ID NO: 69, and SEQ ID NO: 83, or a complement thereof.

In one embodiment, the H. pylori cell envelope polypeptide or a fragment thereof is an H. pylori flagella-associated polypeptide or a fragment thereof encoded by a nucleic acid having a nucleotide sequence of SEQ ID NO: 63, or a complement thereof.

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

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

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

In another embodiment, the H pylori outer membrane polypeptide or a fragment thereof is an H pylori polypeptide having a terminal phenylalanine residue or a fragment thereof encoded by a nucleic acid selected from the group consisting of SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 11, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 26, SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 36, SEQ ID NO: 42, SEQ ID NO: 50, SEQ ID NO: 51, SEQ ID WO 98/24475 PCT[US97/22104 13- NO: 52, SEQ ID NO: 61, SEQ ID NO: 79, SEQ ID NO: 80, SEQ ID NO: 84, SEQ ID NO: 85, SEQ ID NO: 91, and SEQ ID NO: 94, or a complement thereof.

In another embodiment, H. pylori outer membrane polypeptide or a fragment thereof is an H. pylori polypeptide having a terminal phenylalanine residue and a Cterminal tyrosine cluster or a fragment thereof encoded by a nucleic acid selected from the group consisting of SEQ ID NO: 11, SEQ ID NO: 26, SEQ ID NO: 36, SEQ ID NO:.

42, and SEQ ID NO: 52, or a complement thereof.

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

In another embodiment, the H. pylori cell envelope polypeptide or a fragment thereof is an H. pylori flagella-associated polypeptide or a fragment thereof having an amino acid sequence of SEQ ID NO: 160.

In another embodiment, the H. pylori cell envelope polypeptide or a fragment thereof is an .H pylonr iner membrane polypeptide or a fragment thernf Qselecte from the group consisting of SEQ ID NO: 145, SEQ ID NO: 146, SEQ ID NO: 114, SEQ ID NO: 115, SEQ ID NO: 116, SEQ ID NO: 140, SEQ ID NO: 141, SEQ ID NO: 135, and SEQ ID NO: 136.

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

In another embodiment, the H. pylori cell envelope polypeptide or a fragment thereof is an H. pylori outer membrane polypeptide or a fragment thereof selected from the group consisting of SEQ ID NO: 104, SEQ ID NO: 105, SEQ ID NO: 106, SEQ ID NO: 110, SEQ ID NO: 111, SEQ ID NO: 120, SEQ ID NO: 121, SEQ ID NO: 124, SEQ ID NO: 125, SEQ ID NO: 147, SEQ ID NO: 148, SEQ ID NO: 158, SEQ ID NO: 176, WO 98/24475 PCT/US97/22104 14- SEQ ID NO: 177, SEQ ID NO: 181, SEQ ID NO: 182, SEQ ID NO: 188, SEQ ID NO: 191, SEQ ID NO: 102, SEQ ID NO: 108, SEQ ID NO: 123, SEQ ID NO: 133, SEQ ID NO: 139, SEQ ID NO: 149, SEQ ID NO: 119, SEQ ID NO: 126, SEQ ID NO: 127, SEQ ID NO: 162, and SEQ ID NO: 163.

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

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

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

In one embodiment, the H. pylori cytoplasmic polypeptide or a fragment thereof is an H pylori polypeptide or a fragment thereof involved in mRNA translation, wherein the nucleic acid is selected from the group consisting of SEQ ID NO: 57 and SEQ ID LIIL I C.ILuI Q L SI Sc 11V 111 L11%, 1 j.J %J1.lll1 1 I. I J I an%, "AtN. NO: 58, or a complement thereof.

In another embodiment, the H. pylori cytoplasmic polypeptide or a fragment thereof is an H. pylori polypeptide or a fragment thereof involved in genome replication, transcription, recombination and repair, wherein the nucleic acid is selected from the group consisting of SEQ ID NO: 86, SEQ ID NO: 87, or a complement thereof.

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

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

WO 98/24475 PCTIUS97/22104 In another embodiment, the H. pylori cytoplasmic polypeptide or a fragment thereof is an H. pylori polypeptide or a fragment thereof involved in genome replication, transcription, recombination and repair selected from the group consisting of SEQ ID NO: 183 and SEQ ID NO: 184.

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

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

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

Particularly preferred is an isolated nucleic acid having a nucleotide sequence encoding an H. pylori cellular polypeptide or a fragment thereof selected from the group consisting of SEQ ID NO: 112, SEQ ID NO: 113, SEQ ID NO: 118, SEQ ID NO: 130, SEQ ID NO: 134, SEQ ID NO: 137, SEQ ID NO: 138, SEQ ID NO: 144, SEQ ID NO: 151, SEQ ID NO: 152, SEQ ID NO: 153, SEQ ID NO: 156, SEQ ID NO: 159, SEQ ID NO: 165, SEO I

T

NO: 168, SEQ ID NO: 169, SEQ ID NO: 170, SEQ ID NO: 171, SEQ ID NO: 172, SEQ ID NO: 173, and SEQ ID NO: 193.

In another aspect, the invention features a probe having a nucleotide sequence consisting of at least 8 nucleotides of a nucleotide sequence selected from the group consisting of SEQ ID NO: 1-SEQ ID NO: 97, or a complement thereof.

WO 98/24475 PCT[~S97/22104 -16- In another aspect, the invention features an isolated H. pylori polypeptide having an amino acid sequence at least about 60% homologous to an H. pylori polypeptide selected from the group consisting of SEQ ID NO: 98-SEQ ID NO: 194.

In another aspect, the invention features an isolated H. pylori polypeptide which is encoded by a nucleic acid having a nucleotide sequence at least about homologous to a nucleotide sequence selected from the group consisting of SEQ ID NO: 1-SEQ ID NO: 97. In one embodiment, the isolated H. pylori polypeptide is encoded by a nucleotide sequence selected from the group consisting of SEQ ID NO: 1-SEQ ID NO: 97.

In another aspect, the invention features an isolated H. pylori polypeptide which is encoded by a nucleic acid which hybridizes under stringent hybridization conditions to a nucleic acid selected from the group consisting of SEQ ID NO: 1-SEQ ID NO: 97, or a complement thereof.

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

Particularly preferred is an isolated H pylori cell envelope polypeptide or a fragment thereof, wherein the polypeptide is selected from the group consisting of SEQ ID NO: 160, SEQ ID NO: 104, SEQ ID NO: 105, SEQ ID NO: 106, SEQ ID NO: 110, SEQ ID NO: 111, SEQ ID NO: 120, SEQ ID NO: 121, SEQ ID NO: 124, SEQ ID NO: 125, SEQ ID NO: 147, SEQ ID NO: 148, SEQ ID NO: 158, SEQ ID NO: 176, SEQ ID NO: 177, SEQ ID NO: 181, SEQ ID NO: 182, SEQ IDNO: 188, SEQ IDNO: 191, SEQ ID NO: 102, SEQ ID NO: 108, SEQ ID NO: 123, SEQ ID NO: 133, SEQ ID NO: 139, SEQ ID NO: 149, SEQ ID NO: 119, SEQ ID NO: 126, SEQ ID NO: 127, SEQ ID NO: 1 62, SQ D 1Q TT NO 1463, S ID NO: TT N 146. SEQ D NO: 114, SEQ ID NO: 115, SEQ ID NO: 116, SEQ ID NO: 140, SEQ ID NO: 141, SEQ ID NO: 135, SEQ ID NO: 136, SEQ ID NO: 98, SEQ ID NO: 99, SEQ ID NO: 103, SEQ ID NO: 131, SEQ ID NO: 132, SEQ ID NO: 157, SEQ ID NO: 166, and SEQ ID NO: 180.

In one embodiment, the H. pylori cell envelope polypeptide or a fragment thereof is an H. pylori flagella-associated polypeptide or a fragment thereof having an amino acid sequence of SEQ ID NO: 160.

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

WO 98/24475 PCTIUS97/22104 -17- In another embodiment, the H. pylori inner membrane polypeptide or a fragment thereof is an H pylori polypeptide or a fragment thereof involved in transport selected from the group consisting of SEQ ID NO: 145, SEQ ID NO: 146, SEQ ID NO: 114, SEQ ID NO: 115, SEQ ID NO: 116, SEQ ID NO: 140, SEQ ID NO: 141, SEQ ID NO: 135, and SEQ ID NO: 136.

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

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

Particularly preferred is an isolated H pylori cell envelope polypeptide or a fragment thereof, wherein the polypeptide is encoded by a nucleic acid selected from the group consisting of SEQ ID NO: 63, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 23, SEQ ID NO: SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 50, SEQ ID NO: 51, SEQ ID NO: 61, SEQ ID NO: 79, SEQ ID NO: 80, SEQ ID NO: 84, SEQ ID NO: 85, SEQ ID NO: 91, SEQ ID NO: 94, SEQ ID NO: 5, SEQ ID NO: 11, SEQ ID NO: 26, SEQ ID NO: 36, SEQ ID NO: 42, SEQ ID NO: 52, SEQ ID NO: 22, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: SEQ ID NO: 66, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 38, SEQ ID NO: 39, WO 98/24475 PCT/US97/22104 -18- SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 6, SEQ ID NO: 34, SEQ ID NO: 35, SEQ ID NO: 60, and SEQ ID NO: 69, SEQ ID NO: 83.

In one embodiment, the H. pylori cell envelope polypeptide or a fragment thereof is an H. pylori flagella-associated polypeptide or a fragment thereof encoded by a nucleic acid having a nucleotide sequence of SEQ ID NO: 63.

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

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

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

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

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

WO 98/24475 PCT/US97/22104 -19- Particularly preferred is an isolated H. pylori cytoplasmic polypeptide or a fragment thereof, wherein the polypeptide is selected from the group consisting of SEQ ID NO: 154, SEQ ID NO: 155, SEQ ID NO: 183, SEQ ID NO: 184, SEQ ID NO: 185, SEQ ID NO: 186, SEQ ID NO: 189, and SEQ ID NO: 190.

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

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

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

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

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

Particularly preferred is an isolated H pylori cellular polypeptide or a fragment thereof, wherein the polypeptide is selected from the group consisting of SEQ ID NO: 112, SEQ ID NO: 113, SEQ ID NO: 118, SEQ ID NO: 130, SEQ ID NO: 134, SEQ ID NO: 137, SEQ ID NO: 138, SEQ ID NO: 144, SEQ ID NO: 151, SEQ ID NO: 152, SEQ ID NO: 153, SEQ ID NO: 156, SEQ ID NO: 159, SEQ ID NO: 165, SEQ ID NO: 168, SEQ ID NO: 169, SEQ ID NO: 170, SEQ ID NO: 171, SEQ ID NO: 172, SEQ ID NO: 173, and SEQ ID NO: 193.

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

WO 98/24475 PCTfUS97/22104 Particularly preferred is an isolated H. pylori secreted polypeptide or a fragment thereof, wherein the polypeptide is selected from the group consisting of SEQ ID NO: 100, SEQ ID NO: 101, SEQ ID NO: 107, SEQ ID NO: 109, SEQ ID NO: 117, SEQ ID NO: 122, SEQ ID NO: 128, SEQ ID NO: 129, SEQ ID NO: 142, SEQ ID NO: 143, SEQ ID NO: 150 SEQ ID NO: 161, SEQ ID NO: 164, SEQ ID NO: 167, SEQ ID NO: 174, SEQ ID NO: 175, SEQ ID NO: 178, SEQ ID NO: 179, SEQ ID NO: 187, SEQ ID NO: 192, and SEQ ID NO: 194.

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

In another aspect, the invention features a chimeric H. pylori polypeptide comprising at least two H. pylori polypeptides or fragments thereof, wherein the polypeptides are encoded by nucleic acid sequences selected from the group consisting of SEQ ID NO:1-SEQ ID NO:97.

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

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

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

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

Preferably, the vaccine formulation of the invention further includes a pharmaceutically acceptable carrier. In one embodiment, the pharmaceutically acceptable carrier includes an adjuvant. In another embodiment, the pharmaceutically acceptable carrier includes a delivery system, a live vector, a bacteria or a virus. In another embodiment, the pharmaceutically acceptable carrier includes both an adjuvant and a delivery system.

WO 98/24475 PCT/US97/22104 -21 In another aspect, the invention features a method of treating or reducing a risk of H. pylori infection in a subject. The method includes administering to a subject a vaccine formulation of the invention, such that treatment or reduction of risk ofH. pylori infection occurs.

In another aspect, the invention features a method of producing a vaccine formulation of the invention. The method includes combining at least one isolated H.

pylori polypeptide or a fragment thereof selected from the group consisting of SEQ ID NO: 98-SEQ ID NO: 194 with a pharmaceutically acceptable carrier to thereby form a vaccine formulation.

In another aspect, the invention features a method of producing a vaccine formulation of the invention. The method includes culturing a cell under condition that permit expression of an H. pylori polypeptide or a fragment thereof selected from the group consisting of SEQ ID NO: 98-SEQ ID NO: 194; isolating the H. pylori polypeptide from the cell; and combining at least one isolated H. pylori polypeptide or a fragment thereof with a pharmaceutically acceptable carrier to thereby form a vaccine formulation.

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

pylori polypeptides.

In another aspect, the invention features nucleic acids capable of binding mRNA ofH. pylori. Such nucleic acid is capable of acting as antisense nucleic acid to control the translation of mRNA of H. pylori. A further aspect features a nucleic acid which is capable of binding specifically to an H. pylori nucleic acid. These nucleic acids are also referred to herein as complements and have utility as probes and as capture reagents.

In another asnect, the invention features an expression sysvtem cnmnrising an open reading frame corresponding to H. pylori nucleic acid. The nucleic acid further comprises a control sequence compatible with an intended host. The expression system is useful for making polypeptides corresponding to H. pylori nucleic acid.

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

In another aspect, the invention features a method of generating antibodies against H. pylori polypeptides which are capable of binding specifically to H pylori polypeptides. Such antibodies have utility as reagents for immunoassays to evaluate the abundance and distribution of H. pylori-specific antigens.

In another aspect, the invention features a method of generating vaccines for immunizing an individual against H. pylori. The vaccination method includes: immunizing a subject with at least one H. pylori polypeptide according to the present WO 98/24475 PCTIUS97/22104 -22invention, a surface or secreted polypeptide, or active portion thereof, and a pharmaceutically acceptable carrier. Such vaccines have therapeutic and/or prophylactic utilities.

In another aspect, the invention provides a method for generating a vaccine comprising a modified immunogenic H pylori polypeptide, a surface or secreted polypeptide, or active portion thereof, and a pharmacologically acceptable carrier.

In another aspect, the invention features a method of evaluating a compound, e.g.

a polypeptide, a fragment of a host cell polypeptide, for the ability to bind an H.

pylori polypeptide. The method includes: contacting the candidate compound with an H pylori polypeptide and determining if the compound binds or otherwise interacts with an H. pylori polypeptide. Compounds which bind H. pylori are candidates as activators or inhibitors of the bacterial life cycle. These assays can be performed in vitro or in vivo.

pylori nucleic acid, DNA or RNA. The method includes: contacting the candidate compound with an H. pylori nucleic acid and determining if the compound binds or otherwise interacts with an H. pylori polypeptide. Compounds which bind H pylori are candidates as activators or inhibitors of the bacterial life cycle. These assays can be performed in vitro or in vivo.

The invention features H. pylori polypeptides, preferably a substantially pure preparation of an H pylori polypeptide, or a 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 an amino acid sequence of the invention contained in the Sequence Listing, preferably it has about 65% sequence identity with an amino acid sequence of the invention contained in the Sequence Listing, and most preferably it has about 92% to about 99% sequence identity with an amino acid sequence of the invention contained in the Sequence Listing; the polypeptide has an amino acid sequence essentially the same as an amino acid sequence of the invention contained in the Sequence Listing; the polypeptide is at least 5, 10, 2J, 50, 100, or 150 amino acid residues in length; the polypeptide includes 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 contained in the Sequence Listing. In yet another preferred embodiment, the amino acid sequence which differs in sequence identity by about 7% to about 8% from the H pylori amino acid sequences of the invention contained in the Sequence Listing is also encompassed by the invention.

WO 98/24475 PCT/US97/22104 -23- In preferred embodiments: the H. pylori polypeptide is encoded by a nucleic acid of the invention contained in the Sequence Listing, or by a nucleic acid having at least 60%, 70%, 80%, 90%, 95%, 98%, or 99% homology with a nucleic acid of the invention contained in the Sequence Listing.

In a preferred embodiment, the subject H. pylori polypeptide differs in amino acid sequence at 1, 2, 3, 5, 10 or more residues from a sequence of the invention contained in the Sequence Listing. The differences, however, are such that the H. pylori polypeptide exhibits an H. pylori biological activity, the H. pylori polypeptide retains a biological activity of a naturally occurring H. pylori polypeptide.

In preferred embodiments, the polypeptide includes all or a fragment of an amino acid sequence of the invention contained in the Sequence Listing; fused, in reading frame, to additional amino acid residues, preferably to residues encoded by genomic DNA 5' or 3' to the genomic DNA which encodes a sequence of the invention contained in the Sequence Listing.

In yet other preferred embodiments, the H. pylori polypeptide is a recombinant fusion protein having a first H. pylori polypeptide portion and a second polypeptide portion, a second polypeptide portion having an amino acid sequence unrelated to H. pylori. The second polypeptide portion can be, any of glutathione-S-transferase, a DNA binding domain, or a polymerase activating domain. In preferred embodiment the fusion protein can be used in a two-hybrid assay.

Polypeptides of the invention include those which arise as a result of alternative transcription events, alternative RNA splicing events, and alternative translational and postranslational events.

The invention also encompasses an immunogenic component which includes at least one pylori polypeptide in an immunogenic preparation; the immunogenic component being capable of eliciting an immune response specific for the H. pylori polypeptide, a humoral 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 contained in the Sequence Listing.

In another aspect, the invention provides a substantially pure nucleic acid having a nucleotide sequence which 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 an amino acid sequence of the invention contained in the Sequence Listing; the encoded polypeptide has an amino acid sequence essentially the same as an amino acid sequence of the invention contained in the Sequence Listing; the encoded polypeptide is at least 5, 10, 20, 50, 100, or 150 amino acids in length; the encoded WO 98/24475 PCT/US97/22104 -24polypeptide comprises at least 5, preferably at least 10, more preferably at least 20, more preferably at least 50, 100, or 150 contiguous amino acids of the invention contained in the Sequence Listing.

In preferred embodiments: the nucleic acid of the invention is that contained in the Sequence Listing; the nucleic acid is at least 60%, 70%, 80%, 90%, 95%, 98%, or 99% homologous with a nucleic acid sequence of the invention contained in the Sequence Listing.

In a preferred embodiment, the encoded H pylori polypeptide differs by amino acid substitution, addition or deletion of at least one amino acid residue) in amino acid sequence at 1, 2, 3, 5, 10 or more residues, from a sequence of the invention contained in the Sequence Listing. The differences, however, are such that: the H.

pylori encoded polypeptide exhibits a H. pylori biological activity, the encoded H.

pylori enzyme retains a biological activity of a naturally occurring H. pylori.

In preferred embodiments, the encoded polypeptide includes all or a fragment of an amino acid sequence of the invention contained in the Sequence Listing; fused, in reading frame, to additional amino acid residues, preferably to residues encoded by genomic DNA 5' or 3' to the genomic DNA which encodes a sequence of the invention contained in the Sequence Listing.

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

In yet a further preferred embodiment, the nucleic acid which encodes an H.

pylori polypeptide of the invention, hybridizes under stringent conditions to a nucleic acid probe corresponding to at least 8 consecutive nuceotides of the invention contained in the Sequence Listing; more preferably to at least 12 consecutive nucleotides of the invention contained in the Sequence Listing; more preferably to at least 20 consecutive nucleotides of the invention contained in the Sequence Listing; more preferably to at least 40 consecutive nucleotides of the invention contained in the Sequence Listing.

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

In a preferred embodiment, the nucleic acid differs by at least one nucleotide from a nucleotide sequence of the invention contained in the Sequence Listing which encodes amino acids of the invention contained in the Sequence Listing.

In another aspect, the invention encompasses: a vector including a nucleic acid which encodes an H. pylori polypeptide or an H. pylori polypeptide variant as described WO 98/24475 PCT[UJS97/22104 herein; a host cell transfected with the vector; and a method of producing a recombinant H. pylori polypeptide or H. pylori polypeptide variant; including culturing the cell, e.g., in a cell culture medium, and isolating the H. pylori or H. pylori polypeptide variant, from the cell or from the cell culture medium.

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

The invention also provides a probe or primer which includes a substantially purified oligonucleotide. The oligonucleotide includes a region of nucleotide sequence which hybridizes under stringent conditions to at least 8 consecutive nucleotides of sense or antisense sequence of the invention contained in the Sequence Listing, or naturally occurring mutants thereof. In preferred embodiments, the probe or primer further includes a label group attached thereto. The label group can be, a radioisotope, a fluorescent compound, an enzyme, and/or an enzyme co-factor.

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 which is encoded by a nucleic acid which hybridizes under stringent hybridization conditions to a nucleic acid contained in the Sequence Listing.

The invention further provides nucleic acids, RNA or DNA, encoding a polypeptide of the invention. This includes double stranded nucleic acids as well as coding and antisense single strands.

The H. pylori strain, from which genomic sequences have been sequenced, has been deposited in the American Type Culture Collection (ATCC 55679; deposited by Genome Therapeutics Corporation, 100 Beaver Street, Waltham, MA 02154) as strain HP-J99.

Included in the invention are: allelic variations; natural mutants; induced mutants; proteins encoded by DNA that hybridizes under high or low stringency conditions to a nucleic acid which encodes a polypeptide of the invention contained in the Sequence Listing (for definitions of high and low stringency 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, hereby incorporated by reference); and, polypeptides specifically bound by antisera to H.

pylori polypeptides, especially by antisera to an active site or binding domain ofH.

pylori polypeptide. 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.

WO 98/24475 PCT/US97/22104 -26- Putative functions have been determined for several of the H pylori polypeptides of the invention, as shown in Table 1.

Accordingly, uses of the claimed H. pylori polypeptides based on these identified functions, as well as other functions as described herein, are also within the scope of the invention.

In addition, the present invention encompasses H. pylori polypeptides characterized as shown in Table 1 below, including: H. pylori cell envelope proteins, H pylori secreted proteins, H pylori cytoplasmic proteins and H. pylori cellular proteins.

Members of these groups were identified by BLAST homology searches and by searches for secretion signal or transmembrane protein motifs. Polypeptides related by significant homology to the polypeptides of Table 1 are also considered to be classified in the manner of the homologs shown in Table 1.

TABLE 1 ntSeqlD[PCT] aaSeqlD[PCT] A. CELL ENVELOPE A.1 Flagella-associated hp1p13939_24322162 f3 17 63 160 A.2 Outer membrane A.2.1 Terminal phe residue 02ge10116_23462_f2_43 7 104 02ge10116_804550_f2_44 8 105 02ge41622_14875000 c2 65 9 106 01cp20708_214843_c2_49 13 110 01cp20708_4960952 cl 43 14 111 06ae11016 4729625 c3 68 23 120 06ep10615_49068 c2 87 24 121 06gp71906 35158328 f3 85 27 124 06gp71906_3941642_f2_70 28 125 13ae10610 156411 c3 33 50 147 13ae10610_6522827 c3 37 51 148 hp4e53394_11798952_c2_101 61 158 06ge20501_4298568_c3_53 79 176 11ae12004 3367666 c2 41 80 177 hp7e10433_5345837 c3_13 84 181 14ce61516 2460Cq1'i f2 9 85 182 11ap20714_2077_c3_103 91 188 02cp10615_21908138 f1_4 94 191 A.2.2 No terminal phe residue 07gp11909_26460892_f2_6 5 102 A.2.3 Phe and Tyr cluster at Cterminus 02ge41622 34176513 c 150 11 108 WO 98/24475 PTU9/29 PCT[US97/22104 27- 06gp71906 20486556 f2 65 26 123 h p7e10520_14728137_f1i_1 36 133 02ae31010_417818_fM_29 42 139 13ae10610_268553132f3_15 52 149 A.2.4 Via homology hp5p15212_13729635_c3_35 22 119 07ee11402_1046877_c3_100 29 126 14ee41924 1046877 c3 104 30 127 hp1p13939_21641016_f1_1 65 162 hp4p62853_4766691_f3_23 66 163 A.3 Inner membrane A.3.1 Proteins involved in transport 06cp30603 664083 ci94 48 145 09cp10713_36359687_ci_119 49 146 04ep41903_16667055_ci_37 17 114 064ep41903_19689182_ci_43 18 115 14ce31519_24650009_ci_17 19 116 09ce1 0413_26734687_f3_23 43 140 hp6p10904_6726062_f3_13 44 141 A.3.2 Other ~nner membrane proteins 02ae31010 16679640 f2 21 38 135 07ee50709_16679640_f3_60 39 136 A.4 Other cell envelope proteins 01ce61016_1056562_c3_123 1 98 09cp61003_16619192_c2_83 2 99 02ge10116 15632000 c2 114 6 103 04ae61517_12345837_12_4 34 131 04ae61517_21744091_f3_5 35 132 hp4e13394 26750068 c3 113 60 157 hp5p15575_1053590 ci 35 69 166 hp7e10433 5345837 c2 8 83 180 B. CVTnOLASMIC POTEIS B.1. Proteins involved in mRNA translation hp3e1 0946_326094122f3_4 57 154 hp3e10946_34175837_f3_3 58 155 B.2 Proteins involved in genome replication, transcription, recombination and repair 14ce61516_12600937_f2_11 86 183 14cp11908_25402267_c3_104 87 184 B.3 Other cytoplasmic proteins 05ce10910_23712780_-ci_-4 88 185 hp7e10192_23712780_f2_5 89 186 11 ap20714_3466391 023-29 92 189 hp8e10065 4962812f2 18 93 190 C. SECRETED PROTEINS______ 01ce61016 23593955 c3 140 3 100 WO 98/24475 PTU9/20 PCTIUS97/22104 -28- 09cp61003 23593955_ci_79 4 101 02ge41622_20730462_f1_19 10 107 01cp20708_10628177_c2_50 12 109 05ae30220 24415693 c3 175 20 117 06gp10409 4015687 Q2 11 25 122 hp2elO9ll_10213593_ci73 31 128 hp2elO9ll_35567005_c2_88 32 129 09ze1 0333_14571372f3_11 45 142 06cp30603_10744075_c3_136 46 143 12ae1 0622_30273255_fi113 53 150 05ce10208 4707035 c2 17 64 161 06ep30223_176437_c2_134 67 164 hp5p15575_26016387_f2_16 70 167 hp6p12244_4881375_c3_97 77 174 06ce20610_34647187_c2_33 78 175 hp7e10433 36339535_f3_3 81 178 hp7e10433_36339535_f3_3 82 179 hp7e10420_24391078_fi_3 90 187 02ce71018 35720091 c3.4 95 192 hp6e'10363_305170312f3_3 97 194 D. OTHER CELLULAR PROTEINS_____ OlaellOlO 26437877 c2 52 15 112 hp4p33322 5891077 c2 45 16 113 hp3p21118_54628_c3_3 21 118 02ae31010 1064125 fI 11 33 130 hp2elO9ll_15680337_c3_105 37 134 hp2elO9ll_24804577_c3_-104 40 137 hp2elO9ll_32234750_ci_-68 41 138 06cp30603 26070252 c3 140 47 144 03ae10804 235286 f3 19 54 151 09ge11604 4804692 ci 8 55 152 hp2plO6lO 21987687 c2-5 56 153 hp4e13394 26182793 f2 45 5 9 156 hp4e53394 2082126_c2_102 62 159 06ep30223_25402187_ci_112 68 165 hp6e10491_12712706 f3 12 71 168 hp6p12129_12542880 c3 29 72 169 hp6p12129_17067265 c3.29 73 170 hp6p12129 214055 f1 2 74 171 hp6p12129 214055 f3 17 75 172 hp6p12244 33492712 c3 88 761 173 hp1e13054 22360653 f2 4 961 193 [In Table 1, lint" represents nucleotide Seq. ID Seq. ID number] number and "aa" represents amino acid WO 98/24475 PCTIUS97/22104 -29 Definitions The terms "purified polypeptide" and "isolated polypeptide" and "a substantially pure preparation of a polypeptide" are used interchangeably herein and, as used herein, mean a polypeptide that has been substantially, and preferably completely, separated from other proteins, lipids, and nucleic acids with which it naturally occurs. Preferably, the polypeptide is also separated from substances, antibodies or gel matrix, e.g., polyacrylamide, which are used to purify it. Preferably, the polypeptide constitutes at least 10, 20, 50 70, 80 or 95% dry weight of the purified preparation. Preferably, the preparation contains: sufficient polypeptide to allow protein sequencing; at least 1, or 100 pg of the polypeptide; at least 1, 10, or 100 mg of the polypeptide. Furthermore, the terms "purified polypeptide" and "isolated polypeptide" and "a substantially pure preparation of a polypeptide," as used herein, refer to both a polypeptide obtained from nature or produced by recombinant DNA techniques as described herein.

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

The language "substantially free of chemical precursors or other chemicals" includes preparations of H. pylori protein it, which the protein is separated from chemical precusors or other chemicals which are involved in the synthesis of the protein.

In one embodiment, the language "substantially free of chemical precursors or other chemicals" includes preparations ofH. pylori protein having less than about 30% (by dry weight) of chemical precursors or non-H. pylori chemicals, more preferably less than about 20% chemical precursors or non-H. pylori chemicals, still more preferably less WO 98/24475 PCTIUS97/22104 than about 10% chemical precursors or non-H. pylori chemicals, and most preferably less than about 5% chemical precursors or non-H. pylori chemicals.

A purified preparation of cells refers to, in the case of plant or animal cells, an in vitro preparation of cells and not an entire intact plant or animal. In the case of cultured cells or microbial cells, it consists of a preparation of at least 10% and more preferably of the subject cells.

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

A "contig" as used herein is a nucleic acid representing a continuous stretch of genomic sequence of an organism.

An "open reading frame", also referred to herein as ORF, is a region of nucleic acid which encodes a polypeptide. This region may represent a portion of a coding sequence or a total sequence and can be determined from a stop to stop codon or from a start to stop codon.

As used herein, a "coding sequence" is a nucleic acid which is transcribed into messenger RNA and/or translated into a polypeptide wheh placed under the control of appropriate regulatory sequences. The boundaries of the coding sequence are determined by a translation start codon at the five prime terminus and a translation stop code at the three prime terminus. A coding sequence can include but is not limited to messenger NA, synthetic DNA, and recombinant nucleic acid sequences.

A "complement" of a nucleic acid as used herein referes to an anti-parallel or antisense sequence that participates in Watson-Crick base-pairing with the original sequence.

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

WO 98/24475 PCTIUS97/22104 -31- As used herein, the term "probe" refers to a nucleic acid, peptide or other chemical entity which specifically binds to a molecule of interest. Probes are often associated with or capable of associating with a label. A label is a chemical moiety capable of detection. Typical labels comprise dyes, radioisotopes, luminescent and chemiluminescent moieties, fluorophores, enzymes, precipitating agents, amplification sequences, and the like. Similarly, a nucleic acid, peptide or other chemical entity which specifically binds to a molecule of interest and immobilizes such molecule is referred herein as a "capture ligand". Capture ligands are typically associated with or capable of associating with a support such as nitro-cellulose, glass, nylon membranes, beads, particles and the like. The specificity of hybridization is dependent on conditions such as the base pair composition of the nucleotides, and the temperature and salt concentration of the reaction. These conditions are readily discemable to one of ordinary skill in the art using routine experimentation.

Homologous refers to the sequence similarity or sequence identity between two polypeptides or between two nucleic acid molecules. When a position in both of the two compared sequences is occupied by the same base or amino acid monomer subunit, e.g., if a position in each of two DNA molecules is occupied by adenine, then the molecules are homologous at that position. The percent of homology between two sequences is a function of the number of matching or homologous positions shared by the two sequences divided by the number of positions compared x 100. For example, if 6 of of the positions in two sequences are matched or homologous then the two sequences are homologous. By way of example, the DNA sequences ATTGCC and TATGGC share 50% homology. Generally, a comparison is made when two sequences are aligned to give maximum homology.

Nucleic acids are hybridizable to each other when at least ,one strnd f a nnucleic acid can anneal to the other nucleic acid under defined stringency conditions.

Stringency of hybridization is determined by: the temperature at which hybridization and/or washing is performed; and the ionic strength and polarity of the hybridization and washing solutions. Hybridization requires that the two nucleic acids contain complementary sequences; depending on the stringency of hybridization, however, mismatches may be tolerated. Typically, hybridization of two sequences at high stingency (such as, for example, in a solution of 0.5X SSC, at 650 C) requires that the sequences be essentially completely homologous. Conditions of intermediate stringency (such as, for example, 2X SSC at 65 0 C) and low stringency (such as, for example 2X SSC at 550 require correspondingly less overall complementarity between the hybridizing sequences. (1X SSC is 0.15 M NaCI, 0.015 M Na citrate). A preferred, non-limiting example of stringent hybridization conditions are hybridization in 6X WO 98/24475 PCTIUS97/22104 32 sodium chloride/sodium citrate (SSC) at about 450C, followed by one or more washes in 0.2 X SSC, 0.1% SDS at 50-650C.

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

As used herein, the term "surface protein" refers to all surface accessible proteins, e.g. inner and outer membrane proteins, proteins adhering to the cell wall, and secreted proteins.

A polypeptide has H. pylori biological activity if it has one, two and preferably more of the following properties: if when expressed in the course of an H. pylori infection, it can promote, or mediate the attachment ofH. pylori to a cell; it has an enzymatic activity, structural or regulatory function characteristic of an H. pylori protein; the gene which encodes it can rescue a lethal mutation in an H. pylori gene; or it is immunogenic in a subject. A polypeptide has biological activity if it is an antagonist, agonist, or super-agonist of a polypeptide having one of the above-listed properties.

A biologically active fragment or analog is one having an in vivo or in vitro activity which is characteristic of the H. pylori polypeptides of the invention contained in the Sequence Listing, or of other naturally occurring H. pylori polypeptides, one or more of the biological activities described herein. Especially preferred are fragments which exist in vivo, fragments which arise from post transcriptional processing or which arise from translation of alternatively spliced RNA's. Fragments include those expressed in native or endogenous cells as well as those made in expression systems, in CHO cells. Because peptides such as H. pylori polypeptides often exhibit a range of physiological properties and because such properties may be attributable to different portions of the molecule, a useful H. pylori fragment or H. pylori analog is one which exhibits a biological activity in any biological assay for H. pylori activity. Most preferably the fragment or analog possesses 10%, preferably 40%, more preferably 80% or 90% or greater of the activity ofH. pylori, in any in vivo or in vitro assay.

Analogs can differ from naturally occurring H. pylori polypeptides in amino acid sequence or in ways that do not involve sequence, or both. Non-sequence modifications include changes in acetylation, methylation, phosphorylation, carboxylation, or glycosylation. Preferred analogs include H. pylori polypeptides (or biologically act.ve fragments thereof) whose sequences differ from the wild-type sequence by one or more conservative amino acid substitutions or by one or more non-conservative amino acid substitutions, deletions, or insertions which do not substantially diminish the biological activity of the H. pylori polypeptide. Conservative substitutions typically include the substitution of one amino acid for another with similar characteristics, substitutions within the following groups: valine, glycine; glycine, alanine; valine, isoleucine, WO 98/24475 PCT/US97/22104 -33leucine; aspartic acid, glutamic acid; asparagine, glutamine; serine, threonine; lysine, arginine; and phenylalanine, tyrosine. Other conservative substitutions can be made in view of the table below.

TABLE2 CONSERVATIVE AMINO ACID REPLACEMENTS For Amino Acid Code Replace with any of Alanine A D-Ala, Gly, beta-Ala, L-Cys, 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, Gin, D-Gln Aspartic Acid D D-Asp, D-Asn, Asn, Glu, D-Glu, Gin, D-Gln Cysteine C D-Cys, S-Me-Cys, Met, D-Met, Thr, D-Thr Glutamine Q D-Gln, Asn, D-Asn, Glu, D-Glu, Asp, D-Asp Glutamic Acid E D-Glu, D-Asp, Asp, Asn, D-Asn, Gln, D-Gln Glycine G Ala, D-Ala, Pro, D-Pro, P-Ala, Acp Isoleucine I D-Ile, Val, D-Val, Leu, D-Leu, Met, D-Met Leucine L D-Leu, Val, D-Val, Leu, D-Leu, Met, D-Met Lysine K D-Lys, Arg, D-Arg, homo-Arg, D-homo-Arg, Met, D- Met, Ile, D-Ile, Orn, D-Omrn Methionine M D-Met, S-Me-Cys, Ile, D-Ile, Leu, D-Leu, Val, D-Val Phenylalanine F D-Phe, Tyr, D-Thr, L-Dopa, His, D-His, Trp, D-Trp, Trans-3,4, or 5-phenylproline, cis-3,4, or phenylproline Proline P D-Pro, L--thioazolidine-4-carboxylic acid, D-or L- 1oxazolidine-4-carboxylic acid Serine S D-Ser, Thr, D-Thr, allo-Thr, Met, D-Met, Met(O), D-Met(O), L-Cys, D-Cys Threonine T D-Thr, Ser, D-Ser, allo-Thr, Met, DMet, Met(O), D-Met(O), Val, D-Val Tyrosine Y D-Tyr, Phe, D-Phe, L-Dopa, His, D-His Valine V D-Val, Leu, D-Leu, Ile, D-Ile, Met, D-Met Other analogs within the invention are those with modifications which increase peptide stability; such analogs may contain, for exam'le, one or more non-peptide bonds (which replace the peptide bonds) in the peptide sequence. Also included are: analogs that include residues other than naturally occurring L-amino acids, D-amino acids or non-naturally occurring or synthetic amino acids, P or y amino acids; and cyclic analogs.

As used herein, the term "fragment", as applied to an H. pylori analog, will ordinarily be at least about 20 residues, more typically at least about 40 residues, WO 98/24475 PCT/US97/22104 -34preferably at least about 60 residues in length. Fragments of H. pylori polypeptides can be generated by methods known to those skilled in the art. The ability of a candidate fragment to exhibit a biological activity ofH. pylori polypeptide can be assessed by methods known to those skilled in the art as described herein. Also included are H.

pylori polypeptides containing residues that are not required for biological activity of the peptide or that result from alternative mRNA splicing or alternative protein processing events.

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

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

As used herein, the term "transgene" means a nucleic acid (encoding, one or more polypeptides), which is partly or entirely heterologous, foreign, to the transgenic animal or cell into which it is introduced, or, is homologous to an endogenous gene of the transgenic animal or cell into which it is introduced, but which is designed to be inserted, or is inserted, into the cell's genome in such a way as to alter the genome of the cell into which it is inserted it is inserted at a location which differs from that of the natural gene or its insertion results in a knockout). A transgene can include 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 operably linked to the selected nucleic acid, and may include an enhancer sequence.

As used herein, the term "transgenic cell" refers to a cell containing a transgene.

LAs Used hereini a "transgenic animal" is 1 1 a lnimal in which one or moreII l and preferably essentially all, of the cells of the animal includes a transgene. The transgene can be introduced into the cell, directly or indirectly by introduction into a precursor of the cell, by way of deliberate genetic manipulation, such as by a process of transformation of competent cells or by microinjection or by infection with a recombinant virus. This molecule may be integrated within a chromosome, or it may be extrachromosomallv re;plicating DNA.

The term "antibody" as used herein is intended to include fragments thereof which are specifically reactive with H. pylori polypeptides.

As used herein, the term "cell-specific promoter" means a DNA sequence that serves as a promoter, regulates expression of a selected DNA sequence operably linked to the promoter, and which effects expression of the selected DNA sequence in specific cells of a tissue. The term also covers so-called "leaky" promoters, which WO 98/24475 PCT/US97/22104 regulate expression of a selected DNA primarily in one tissue, but cause expression in other tissues as well.

Misexpression, as used herein, refers to a non-wild type pattern of gene expression. It includes: expression at non-wild type levels, over or under expression; a pattern of expression that differs from wild type in terms of the time or stage at which the gene is expressed, increased or decreased expression (as compared with wild type) at a predetermined developmental period or stage; a pattern of expression that differs from wild type in terms of decreased expression (as compared with wild type) in a predetermined cell type or tissue type; a pattern of expression that differs from wild type in terms of the splicing size, amino acid sequence, posttransitional modification, or biological activity of the expressed polypeptide; a pattern of expression that differs from wild type in terms of the effect of an environmental stimulus or extracellular stimulus on expression of the gene, a pattern of increased or decreased expression (as compared with wild type) in the presence of an increase or decrease in the strength of the stimulus.

As used herein, "host cells" and other such terms denoting microorganisms or higher eukaryotic cell lines cultured as unicellular entities refers to cells which can become or have been used as recipients for a recombinant vector or other transfer DNA, and include the progeny of the original cell which has been transfected. It is understood by individuals skilled in the art that the progeny of a single parental cell may not necessarily be completely identical in genomic or total DNA compliment to the original parent, due to accident or deliberate mutation.

As used herein, the term "control sequence" refers to a nucleic acid having a base sequence which is recognized by the host organism to effect the expression of encoded sequences to which they are ligated. The nature of such control sequences differs depending upon the host organism; in prokaryotes, such control sequences generally include a promoter, ribosomal binding site, terminators, and in some cases operators; in eukaryotes, generally such control sequences include promoters, terminators and in some instances, enhancers. The term control sequence is intended to include at a minimum, all components whose presence is necessary for expression, and may also include additional components whose presence is advantageous, for example, leader sequences.

As used herein, the term "operably linked" refers to sequences joined or ligated to function in their intended manner. For example, a control sequence is operably linked to coding sequence by ligation in such a way that expression of the coding sequence is achieved under conditions compatible with the control sequence and host cell.

WO 98/24475 PCTIUTS97/22104 -36- The metabolism of a substance, as used herein, means any aspect of the, expression, function, action, or regulation of the substance. The metabolism of a substance includes modifications, covalent or non-covalent modifications of the substance. The metabolism of a substance includes modifications, covalent or noncovalent modification, the substance induces in other substances. The metabolism of a substance also includes changes in the distribution of the substance. The metabolism of a substance includes changes the substance induces in the distribution of other substances.

A "sample" as used herein refers to a biological sample, such as, for example, tissue or fluid isloated from an individual (including without limitation plasma, serum, cerebrospinal fluid, lymph, tears, saliva and tissue sections) or from in vitro cell culture constituents, as well as samples from the environment.

The practice of the invention will employ, unless otherwise indicated, conventional techniques of chemistry, molecular biology, microbiology, recombinant DNA, and immunology, which are within the skill of the art. Such techniques are explained fully in the literature. See Sambrook, Fritsch, and Maniatis, Molecular Cloning; Laboratory Manual 2nd ed. (1989); DNA Cloning, Volumes I and II (D.N Glover ed. 1985); Oligonucleotide Synthesis Gait ed, 1984); Nucleic Acid Hybridization Hames S.J. Higgins eds. 1984); the series, Methods in Enzymoloqy (Academic Press, Inc.), particularly Vol. 154 and Vol. 155 (Wu and Grossman, eds.) and PCR-A Practical Approach (McPherson, Quirke, and Taylor, eds., 1991).

I. Isolation of Nucleic Acids ofH. pylori and Uses Therefor H. pylori Genomic Sequence This invention provides nucleotide sequences of the genome ofH. pylori which thus comprises a DNA sequence library of H. pylori genomic DNA. The detailed description that follows provides nucleotide sequences ofH. pylori, and also describes how the sequences were obtained and how ORFs and protein-coding sequences were identified. Also described are methods of using the disclosed H. pylori sec uences in methods including diagnostic and therapeutic applications. Furthermore, the library can be used as a database for identification and comparison of medically important sequences in this and other strains of H. pylori.

To determine the genomic sequence of H. pylori, DNA was isolated from a strain of H pylori (ATCC 55679; deposited by Genome Therapeutics Corporation, 100 Beaver Street, Waltham, MA 02154) and mechanically sheared by nebulization to a WO 98/24475 PCTIUS97/22104 -37median size of 2 kb. Following size fractionation by gel electrophoresis, the fragments were blunt-ended, ligated to adapter oligonucleotides, and cloned into each of different pMPX vectors (Rice et al., abstracts of Meeting of Genome Mapping and Sequencing, Cold Spring Harbor, NY, 5/11-5/15, 1994, p. 225) to construct a series of "shotgun" subclone libraries.

DNA sequencing was achieved using multiplex sequencing procedures essentially as disclosed in Church et al., 1988, Science 240:185; U.S. Patents No.

4,942,124 and 5,149,625). DNA was extracted from pooled cultures and subjected to chemical or enzymatic sequencing. Sequencing reactions were resolved by electrophoresis, and the products were transferred and covalently bound to nylon membranes. Finally, the membranes were sequentially hybridized with a series of labelled oligonucleotides complimentary to "tag" sequences present in the different shotgun cloning vectors. In this manner, a large number of sequences could be obtained from a single set of sequencing reactions. The cloning and sequencing procedures are described in more detail in the Exemplification.

Individual sequence reads obtained in this manner were assembled using the FALCONTM program (Church et al., 1994, Automated DNA Sequencing and Analysis, J.C. Venter, ed., Academic Press) and PHRAP Green, Abstracts of DOE Human Genome Program Contractor-Grantee Workshop V, Jan. 1996, p.157). The average contig length was about 3-4 kb.

A variety of approaches are used to order the contigs so as to obtain a continuous sequence representing the entire H. pylori genome. Synthetic oligonucleotides are designed that are complementary to sequences at the end of each contig. These oligonucleotides may be hybridized to libaries of H. pylori genomic DNA in, for example, lambda phage vectors or plasmid v1etnr to identify clones that contain YIIU II F-5- I lb sequences corresponding to the junctional regions between individual contigs. Such clones are then used to isolate template DNA and the same oligonucleotides are used as primers in polymerase chain reaction (PCR) to amplify junctional fragments, the nucleotide sequence of which is then determined.

The H. pylori sequences were analyzed for the presence of open reading frames (ORFs) comprising at least 180 nucleotides As a result of the analysis of ORFs based on stop-to-stop codon reads, it should be understood that these ORFs may not correspond to the ORF of a naturally-occurring H. pylori polypeptide. These ORFs may contain start codons which indicate the initiation of protein synthesis of a naturallyoccurring H. pylori polypeptide. Such start codons within the ORFs provided herein can be identified by those of ordinary skill in the relevant art, and the resulting ORF and the encoded H. pylori polypeptide is within the scope of this invention. For example, within WO 98/24475 PCTI/US97/22104 -38the ORFs a codon such as AUG or GUG (encoding methionine or valine) which is part of the initiation signal for protein synthesis can be identified and the ORF modified to correspond to a naturally-occurring H. pylori polypeptide. The predicted coding regions were defined by evaluating the coding potential of such sequences with the program GENEMARKTM (Borodovsky and Mclninch, 1993, Comp. Chem. 17:123).

Other H. pylori Nucleic Acids The nucleic acids of this invention may be obtained directly from the DNA of the above referenced H. pylori strain by using the polymerase chain reaction (PCR). See "PCR, A Practical Approach" (McPherson, Quirke, and Taylor, eds., IRL Press, Oxford, UK, 1991) for details about the PCR. High fidelity PCR can be used to ensure a faithful DNA copy prior to expression. In addition, the authenticity of amplified products can be checked by conventional sequencing methods. Clones carrying the desired sequences described in this invention may also be obtained by screening the libraries by means of the PCR or by hybridization of synthetic oligonucleotide probes to filter lifts of the library colonies or plaques as known in the art (see, Sambrook et al., Molecular Cloning, A Laboratory Manual 2nd edition, 1989, Cold Spring Harbor Press, NY).

It is also possible to obtain nucleic acids encoding H. pylori polypeptides from a cDNA library in accordance with protocols herein described. A cDNA encoding an H pylori polypeptide can be obtained by isolating total mRNA from an appropriate strain.

Double stranded cDNAs can then be prepared from the total mRNA. Subsequently, the cDNAs can be inserted into a suitable plasmid or viral bacteriophage) vector using any one of a number 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 .provided by the invention. The nucleic acids of the invention can be DNA or RNA. Preferred nucleic acids of the invention are contained in the Sequence Listing.

The nucleic acids of the invention can also be chemically synthesized using standard techniques. Various methods of chemically synthesizing polydeoxynucleotides are known, including solid-phase synthesis which, like peptide synthesis, has been fully automated in commercially available DNA synthesizers (See Itakura et al. U.S.

Patent No. 4,598,049; Caruthers et al. U.S. Patent No. 4,458,066; and Itakura U.S.

Patent Nos. 4,401,796 and 4,373,071, incorporated by reference herein).

Nucleic acids isolated or synthesized in accordance with features of the present invention are useful, by way of example, without limitation, as probes, primers, capture ligands, antisense genes and for developing expression systems for the synthesis of proteins and peptides corresponding to such sequences. As probes, primers, capture WO 98/24475 PCT/US97/22104 -39ligands and antisense agents, the nucleic acid normally consists of all or part (approximately twenty or more nucleotides for specificity as well as the ability to form stable hybridization products) of the nucleic acids of the invention contained in the Sequence Listing. These uses are described in further detail below.

Probes A nucleic acid isolated or synthesized in accordance with the sequence of the invention contained in the Sequence Listing can be used as a probe to specifically detect H pylori. With the sequence information set forth in the present application, sequences of twenty or more nucleotides are identified which provide the desired inclusivity and exclusivity with respect to H. pylori, and extraneous nucleic acids likely to be encountered during hybridization conditions. More preferably, the sequence will comprise at least twenty to thirty nucleotides to convey stability to the hybridization product formed between the probe and the intended target molecules.

Sequences larger than 1000 nucleotides in length are difficult to synthesize but can be generated by recombinant DNA techniques. Individuals skilled in the art will readily recognize that the nucleic acids, for use as probes, can be provided with a label to facilitate detection of a hybridization product.

Nucleic acid isolated and synthesized in accordance with the sequence of the invention contained in the Sequence Listing can also be useful as probes to detect homologous regions (especially homologous genes) of other Helicobacter species using appropriate stringency hybridization conditions as described herein.

Capture Ligand For use as a capture ligand, the nucleic acid selected in the manner described above with respect to probes, can be readily associated with a support. The manner in .C 1ca nucleic 13 l with supports is vell ,ula;. acid having twenty or more nucleotides in a sequence of the invention contained in the Sequence Listing have utility to separate H. pylori nucleic acid from the nucleic acid of each other and other organisms. Nucleic acid having twenty or more nucleotides in a sequence of the invention contained in the Sequence Listing can also have utility to separate other Helicobacter species from each other and from other organisms. Preferably, the sequence will comprise at least twenty nucleotides to convey stability to the hybridization product formed between the probe and the intended target molecules.

Sequences larger than 1000 nucleotides in length are difficult to synthesize but can be generated by recombinant DNA techniques.

WO 98/24475 PCTIUS97/22104 Primers Nucleic acid isolated or synthesized in accordance with the sequences described herein have utility as primers for the amplification of H. pylori nucleic acid. These nucleic acids may also have utility as primers for the amplification of nucleic acids in other Helicobacter species. With respect to polymerase chain reaction (PCR) techniques, nucleic acid sequences of 10-15 nucleotides of the invention contained in the Sequence Listing have utility in conjunction with suitable enzymes and reagents to create copies of H. pylori nucleic acid. More preferably, the sequence will comprise twenty or more nucleotides to convey stability to the hybridization product formed between the primer and the intended target molecules. Binding conditions of primers greater than 100 nucleotides are more difficult to control to obtain specificity. High fidelity PCR can be used to ensure a faithful DNA copy prior to expression. In addition, amplified products can be checked by conventional sequencing methods.

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

Antisense Nucleic acid or nucleic acid-hybridizing derivatives isolated or synthesized in accordance with the sequences described herein have utility as antisense agents to prevent the expression ofH. pylori genes. These sequences also have utility as antisense agents to prevent expression of genes of other Helicobacter species.

In one embodiment, nucleic acid or derivatives corresponding to H. pylori nucleic acids is loaded into a suitable carrier such as a liposome or bacteriophage for introduction into bacterial cells. For example, a nucleic acid having twenty or more nucleotides is capable of binding to bacteria nucleic acid or bacteria messenger RNA.

Preferably, the antisense nucleic acid is comprised of 20 or more nucleotides to provide necessary stability of a hybridization product of non-naturally occurring nucleic acid and bacterial nucleic acid and/or bacterial messenger RNA. Nucle;c zid having a sequence greater than 1000 nucleotides in length is difficult to synthesize but can be generated by recombinant DNA techniques. Methods for loading antisense nucleic acid in liposomes is known in the art as exemplified by U.S. Patent 4,241,046 issued December 23, 1980 to Papahadjopoulos et al.

WO 98/24475 PCTIUS97/22104 -41- II. Expression ofH. pylori Nucleic Acids Nucleic acid isolated or synthesized in accordance with the sequences described herein have utility to generate polypeptides. The nucleic acid of the invention exemplified in the Sequence Listing or fragments of the nucleic acid encoding active portions of H. pylori polypeptides can be cloned into suitable vectors or used to isolate nucleic acid. The isolated nucleic acid is combined with suitable DNA linkers and cloned into a suitable vector.

The function of a specific gene or operon can be ascertained by expression in a bacterial strain under conditions where the activity of the gene product(s) specified by the gene or operon in question can be specifically measured. Alternatively, a gene product may be produced in large quantities in an expressing strain for use as an antigen, an industrial reagent, for structural studies, etc. This expression can be accomplished in a mutant strain which lacks the activity of the gene to be tested, or in a strain that does not produce the same gene product(s). This includes, but is not limited to other Helicobacter strains, or other bacterial strains such as E. coli, Norcardia, Corynebacterium, Campylobacter, and Streptomyces species. In some cases the expression host will utilize the natural Helicobacter promoter whereas in others, it will be necessary to drive the gene with a promoter sequence derived from the expressing organism an E. coli beta-galactosidase promoter for expression in E. coli).

To express a gene-product using the natural H. pylori promoter, a procedure such as the following can be used. A restriction fragment containing the gene of interest, together with its associated natural promoter element and regulatory sequences (identified using the DNA sequence data) is cloned into an appropriate recombinant plasmid containing an origin of replication that functions in the host organism and an appropriate selectable marker. This can be accomplished by a number of procedures known to those skilled in the art. It is most preferably done by cutting the plasmid and the fragment to be cloned with the same restriction enzyme to produce compatible ends that can be ligated to join the two pieces together. The recombinant plasmid is introduced into the host organism by, for example, electroporation and cells containing the recombinant plasmid are identified by selection for the marker on the plasmid.

Expression of the desired gene prouct is detected using an assay specific for that gene product.

In the case of a gene that requires a different promoter, the body of the gene (coding sequence) is specifically excised and cloned into an appropriate expression plasmid. This subcloning can be done by several methods, but is most easily accomplished by PCR amplification of a specific fragment and ligation into an WO 98/24475 PCTIUS9722104 -42expression plasmid after treating the PCR product with a restriction enzyme or exonuclease to create suitable ends for cloning.

A suitable host cell for expression of a gene can be any procaryotic or eucaryotic cell. For example, an 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 cell (CHO). Other suitable host cells are known to those skilled in the art.

Expression in eucaryotic cells such as mammalian, yeast, or insect cells can lead to partial or complete glycosylation and/or formation of relevant inter- or intra-chain disulfide bonds of a recombinant peptide product. Examples of vectors for expression in yeast S. cerivisae include pYepSecl (Baldari. et al., (1987) Embo J. 6:229-234), pMFa (Kurjan and Herskowitz, (1982) Cell 30:933-943), pJRY88 (Schultz et al., (1987) Gene 54:113-123), and pYES2 (Invitrogen Corporation, San Diego, CA). Baculovirus vectors available for expression of proteins 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, and Summers, (1989) Virology 170:31-39). Generally, COS cells (Gluzman, (1981) Cell 23:175-182) are used in conjunction with such vectors as pCDM 8 (Aruffo, A. and Seed, (1987) Proc. Natl. Acad. Sci. USA 84:8573-8577) for transient 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. Vector DNA can be introduced into mammalian cells via conventional techniques such as calcium phosphate or calcium chloride co-precipitation, DEAE-dextran-mediated transfection, or electroporation. Suitable methods for transforming host cells can be found in Sambrook et al. (Molecular Cloning: A Laboratory Manual, 2nd Edition, Cold Spring Harbor Laboratory press (1989)), and other laboratory textbooks.

,.JpAA h .LCJ. L aUV Ir UL.JI jIC3 I\1 l uJ VLL LII I(UIV l ,.LIJ L.ALLUIJI'.

Expression in procaryotes is most often carried out in E. coli with either fusion or non-fusion inducible expression vectors. Fusion vectors usually add a number of

NH

2 terminal amino acids to the expressed target gene. These NH 2 terminal amino acids often are referred to as a reporter group. Such reporter groups usually serve two purposes: 1) to increase the solubility of the target recombinant protein; and 2) to aid in the prification of the target recombinant protein by acting as a ligand in affinity purification. Often, in fusion expression vectors, a proteolytic cleavage site is introduced at the junction of the reporter group and the target recombinant protein to enable separation of the target recombinant protein from the reporter group subsequent to purification of the fusion protein. Such enzymes, and their cognate recognition sequences, include Factor Xa, thrombin and enterokinase. Typical fusion expression vectors include pGEX (Amrad Corp., Melbourne, Australia), pMAL (New England WO 98/24475 PCTIS97/22104 -43- Biolabs, Beverly, MA) and pRIT5 (Pharmacia, Piscataway, NJ) which fuse glutathione S-transferase, maltose E binding protein, or protein A, respectively, to the target recombinant protein. A preferred reporter group is poly(His), which may be fused to the amino or carboxy terminus of the protein and which renders the recombinant fusion protein easily purifiable by metal chelate chromatography.

Inducible non-fusion expression vectors include pTrc (Amann et al., (1988) Gene 69:301-315) and pET1 Id (Studier et al., Gene Expression Technology: Methods in Enzvmology 185, Academic Press, San Diego, California (1990) 60-89). While target gene expression relies on host RNA polymerase transcription from the hybrid trp-lac fusion promoter in pTrc, expression of target genes inserted into pET1 Id relies on transcription from the T7 gnlO-lac 0 fusion promoter mediated by coexpressed viral RNA polymerase (T7 gnl). This viral polymerase is supplied by host strains BL21(DE3) or HMS174(DE3) from a resident X prophage harboring a T7 gnl under the transcriptional control of the lacUV 5 promoter.

For example, a host cell transfected with a nucleic acid vector directing expression of a nucleotide sequence encoding an H. pylori polypeptide can be cultured under appropriate conditions to allow expression of the polypeptide to occur. The polypeptide may be secreted and isolated from a mixture of cells and medium containing the peptide. Alternatively, the polypeptide may be retained cytoplasmically and the cells harvested, lysed and the protein isolated. A cell culture includes host cells, media and other byproducts. Suitable media for cell culture are well known in the art.

Polypeptides of the invention can be isolated from cell culture medium, host cells, or both using techniques known in the art for purifying proteins including ion-exchange chromatography, gel filtration chromatography, ultrafiltration, electrophoresis, and immunoaffinity purification with antibodies specific for such polypeptides.

Additionally, in many situations, polypeptides can be produced by chemical cleavage of a native protein tryptic digestion) and the cleavage products can then be purified by standard techniques.

In the case of membrane bound proteins, these can be isolated from a host cell by contacting a membrane-associated protein fraction with a detergent forming a solubilized complex, where the membrane-associated protein is no longer entirely embedded in the membrane fraction and is solubilized at least to an extent which allows it to be chromatographically isolated from the membrane fraction. Several different criteria are used for choosing a detergent suitable for solubilizing these complexes. For example, one property considered is the ability of the detergent to solubilize the H.

pylori protein within the membrane fraction at minimal denaturation of the membraneassociated protein allowing for the activity or functionality of the membrane-associated WO 98/24475 PCT/US97/22104 -44protein to return upon reconstitution of the protein. Another property considered when selecting the detergent is the critical micelle concentration (CMC) of the detergent in that the detergent of choice preferably has a high CMC value allowing for ease of removal after reconstitution. A third property considered when selecting a detergent is the hydrophobicity of the detergent. Typically, membrane-associated proteins are very hydrophobic and therefore detergents which are also hydrophobic, the triton series, would be useful for solubilizing the hydrophobic proteins. Another property important to a detergent can be the capability of the detergent to remove the H. pylori protein with minimal protein-protein interaction facilitating further purification. A fifth property of the detergent which should be considered is the charge of the detergent. For example, if it is desired to use ion exchange resins in the purification process then preferably detergent should be an uncharged detergent. Chromatographic techniques which 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 recombinant H. pylori peptide expression in E. coli is to express the protein in a host bacteria with an impaired capacity to proteolytically cleave the recombinant protein (Gottesman, Gene Expression Technology: Methods in Enzvmology 185, Academic Press, San Diego, California (1990) 119-128). Another strategy would be to alter the nucleic acid encoding an H. pylori peptide to be inserted into an expression vector so that the individual codons for each amino acid would be those preferentially utilized in highly expressed E. coli proteins (Wada et al., (1992) Nuc. Acids Res. 20:2111-2118). Such alteration of nucleic acids of the invention can be carried out by standard DNA synthesis techniques.

The nucleic acids of the invention can also be chemically synthesized using standard techniques. Various methods of chemically synthesizing polydeoxynucleotides are known, including solid-phase synthesis which, like peptide synthesis, has been fully automated in commercially available DNA synthesizers (See, Itakura et al. U.S.

Patent Nos. 4,401,796 and 4,373,071, incorporated by reference herein).

III. H. pylori Polvpeptides This invention encompasses isolated H. pylori polypeptides encoded by the disclosed H. pylori genomic sequences, including the polypeptides of the invention contained in the Sequence Listing. Polypeptides of the invention are preferably at least 5 amino acid residues in length. Using the DNA sequence information provided herein, the amino acid sequences of the polypeptides encompassed by the invention can be deduced using methods well-known in the art. It will be understood that the sequence of WO 98/24475 PCTIUS97/22104 an entire nucleic acid encoding an H. pylori polypeptide can be isolated and identified based on an ORF that encodes only a fragment of the cognate protein-coding region.

This can be acheived, for example, by using the isolated nucleic acid encoding the ORF, or fragments thereof, to prime a polymerase chain reaction with genomic H. pylori DNA as template; this is followed by sequencing the amplified product.

The polypeptides of the invention can be isolated from wild-type or mutant H.

pylori cells or from heterologous organisms or cells (including, but not limited to, bacteria, yeast, insect, plant and mammalian cells) into which an H. pylori nucleic acid has been introduced and expressed. In addition, the polypeptides can be part of recombinant fusion proteins.

H pylori polypeptides of the invention can be chemically synthesized using commercially automated procedures such as those referenced herein.

H pylori polypeptides of the invention are also intended to include chimeric proteins and truncated proteins as decribed herein.

Chimeric H. pylori proteins H. pylori chimeric polypeptides comprise one or more H pylori polypeptides fused together. These combined sequences can be made by combining two or more genes, or two or more polypeptide encoding sequences, or at least one gene and at least one polypeptide encoding sequence in tandem, and the subsequent expression of the encoded proteins by conventional molecular biological techniques. The combined nucleotide sequences may be composed of a combination of either full length H pylori nucleotide sequences or fragments of such sequences, fragments which contain immunologically relevant portions of the encoded H. pylori protein. These chimeric H.

pylori proteins then contain the combined or synergistic vaccine potential of each individual H pylori protein sequence and can be used in vaccine formulations of the invention.

Truncated gene expression and protein production H. pylori proteins encoded by a given nucleotide sequence can also be used in a biologically active truncated form. Such truncation can be produced, for example, by the elimination of either 5' and/or 3' regions of the encoding nucleotide sequence.

These truncations can affect recombinant expression of the encoded protein and/or subsequent purification of the protein. For example, truncation of a nucleotide sequence encoding a predicted export sequence of a specific protein may alter expression of the protein. Alternatively, C-terminal truncation of an H. pylori polypeptide by elimination of the 3' end of the nucleic acid coding region may also improve protein expression and WO 98/24475 PCTfUS97/22104 -46subsequent purification and use, as is outlined in Example VIII below. Deletion of nucleic acid regions encoding internal H. pylori protein regions can also result in improved protein expression, purification and/or efficacy as a vaccine candidate.

IV. Identification of Nucleic Acids Encoding Vaccine Components and Targets for Agents Effective Against H. pvylori The disclosed H. pylori genome 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 encompasses nucleic acids encoding immunogenic components of vaccines and targets for agents effective against H. pylori. Identification of said immunogenic components involved in the determination of the function of the disclosed sequences can be achieved using a variety of approaches. Non-limiting examples of these approaches are described briefly below.

Homology to known sequences: Computer-assisted comparison of the disclosed H. pylori sequences with previously reported sequences present in publicly available databases is useful for identifying functional H. pylori nucleic acid and polypeptide sequences. It will be understood that protein-coding sequences, for example, may be compared as a whole, and that a high degree of sequence homology between two proteins (such as, for example, >80-90%) at the amino acid level indicates that the two proteins also possess some degree of functional homology, such as, for example, among enzymes involved in metabolism, DNA synthesis, or cell wall synthesis, and proteins involved in transport, cell division, etc. In addition, many structural features of particular protein classes have been identified and correlate with specific consensus sequences, such as, for example, binding domains for nucleotides, DNA, metalions, and other small molecules; sites for covalent modifications such as phosphorylation, acylation, and the like; sites of protein:protein interactions, etc. These consensus sequences may be quite short and thus may represent only a fraction of the entire protein-coding sequence. Identification of such a feature in an H. pylori sequence is therefore useful in determining the function of the encoded protein and identifying useful targets of antibacterial drugs.

Of particular relevance to the present invention are structural features that are common to secretory, transmembrane, and surface proteins, including secretion signal peptides and hydrophobic transmembrane domains. H. pylori proteins identified as containing putative signal sequences and/or transmembrane domains are useful as immunogenic components of vaccines.

WO 98/24475 PCTIUS97/22104 -47- Identification of essential genes: Nucleic acids that encode proteins essential for growth or viability of H. pylori are preferred drug targets. H. pylori genes can be tested for their biological relevance to the organism by examining the effect of deleting and/or disrupting the genes, by so-called gene "knockout", using techniques known to those skilled in the relevant art. In this manner, essential genes may be identified.

Strain-specific sequences: Because of the evolutionary relationship between different H pylori strains, it is believed that the presently disclosed H. pylori sequences are useful for identifying, and/or discriminating between, previously known and new H.

pylori strains. It is believed that other H. pylonri strains will exhibit at least sequence homology with the presently disclosed sequence. Systematic and routine analyses of DNA sequences derived from samples containing H. pylori strains, and comparison with the present sequence allows for the identification of sequences that can be used to discriminate between strains, as well as those that are common to all H. pylori strains. In one embodiment, the invention provides nucleic acids, including probes, and peptide and polypeptide sequences that discriminate between different strains of H.

pylori. Strain-specific components can also be identified functionally by 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 Candidate Protein Antigens For Antibody And Vaccine Development The selection of candidate protein antigens for vaccine development can be 4 .1 cr the c e;n, ,i ,,1ypePti. First, the OnuRF's can be analyzed for homology to other known exported or membrane proteins and analyzed using the discriminant analysis described by Klein, et al. (Klein, Kanehsia, and DeLisi, C. (1985) Biochimica et Biophysica Acta 815,468-476) for predicting exported and membrane proteins.

.Homology searches can be performed using the BLAST algorithm contained in the Wisconsin Sequence Analysis Package (Genetics Computer Group, Unlve.sity Research Park, 575 Science Drive, Madison, WI 53711) to compare each predicted ORF amino acid sequence with all sequences found in the current GenBank, SWISS-PROT and PIR databases. BLAST searches for local alignments between the ORF and the databank sequences and reports a probability score which indicates the probability of finding this sequence by chance in the database. ORF's with significant homology (e.g.

probabilities lower than 1 x 0-6 that the homology is only due to random chance) to WO 98/24475 PCT/US97/22104 -48membrane or exported proteins represent protein antigens for vaccine development.

Possible functions can be provided to H. pylori genes based on sequence homology to genes cloned in other organisms.

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

Surface exposed outer membrane proteins are likely to represent the best antigens to provide a protective immune response against H pylori. Among the algorithms that can be used to aid in prediction of these outer membrane proteins include the presence of an amphipathic beta-sheet 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) approximately at positions 1, 3, 5, 7 and 9 from the C-terminus see Figure 1, block Importantly, these sequences have not been detected at the C-termini of periplasmic proteins, thus allowing preliminary distinction between these classes of proteins based on primary sequence data. This phenomenon has been reported previously by Struyve et al. Mol.

Biol. 218:141-148, 1991).

Also illustrated in Figure 1 are additional amino acid sequence motifs found in many outer membrane proteins ofH. pylori. The amino acid sequence alignment in Figure 1 depicts portions of the sequence of five H. pylori proteins (depicted in the single Icttcr amino acid code) labeled with their amino acid Sequence !D Numbers and shown N-terminal to C-terminal, left to right. Six distinct blocks (labeled A through F) of similar amino acid residues are found including the distinctive hydrophobic residues (Phe or Tyr; F or Y according to the single letter code for amino acid residues) frequently found at positions near the C-terminus of outer membrane proteins. The presence of several shared motifs clearly establishes the similarity between members of this group of proteins.

In addition, outer membrane proteins isolated from H. pylori frequently share a motif near the mature N-terminus after processing to remove the secretion signal) as illustrated in the blocked amino acid residues in Figure 2. Figure 2 depicts the Nterminal portion of three H. pylori proteins (designated by their amino acid Sequence ID Numbers and shown N-terminal to C-terminal, left to right).

WO 98/24475 PCT/S97/22104 -49- One skilled in the art would know that these shared sequence motifs are highly significant and establish a similarity among this group of proteins.

Infrequently it is not possible to distinguish between multiple possible nucleotides at a given position in the nucleic acid sequence. In those cases the ambiguities are denoted by an extended alphabet as follows: These are the official IUPAC-IUB single-letter base codes Code

G

A

T

C

R

Y

M

K

S

W

H

B

V

D

N

Base Description Guanine Adenine Thymine Cytosine Purine Pyrimidine Amino Ketone Strong interaction Weak interaction Not-G Not-A Not-T (not-U) Not-C Any (A or G) (C or T or U) (A or C) (G or T) (C or G) (A or T) (A or C or T) (C or G or T) (A or C or G) (A or G or T) (A or C or G or T) The amino acid translations of this invention account for the ambiguity in the nucleic acid sequence by translating the ambiguous codon as the letter In all cases, the permissible amino acid residues at a position are clear from an examination of the nucleic acid sequence based on the standard genetic code.

V. Production of Fragments and Analogs of H. pylori Nucleic Acids and Polypeptides Based op the discovery of the H. pylori gene products of the invention provided in the Sequence Lsiting, one skilled in the art can alter the disclosed structure (of H.

pylori genes), by producing fragments or analogs, and test the newly produced structures for activity. Examples of techniques known to those skilled in the relevant art which allow the production and testing of fragments and analogs are discussed below.

These, or analogous methods can be used to make and screen libraries of polypeptides, WO 98/24475 PCT/U~S97/22104 libraries of random peptides or libraries of fragments or analogs of cellular proteins for the ability to bind H. pylori polypeptides. Such screens are useful for the identification of inhibitors of H. pylori.

Generation of Fragments Fragments of a protein can be produced in several ways, recombinantly, by proteolytic digestion, or by chemical synthesis. Internal or terminal fragments of a polypeptide can be generated by removing one or more nucleotides from one end (for a terminal fragment) or both ends (for an internal fragment) of a nucleic acid which encodes the polypeptide. Expression of the mutagenized DNA produces polypeptide fragments. Digestion with "end-nibbling" endonucleases can thus generate DNA's which encode an array of fragments. DNA's which encode fragments of a protein can also be generated by random shearing, restriction digestion or a combination of the above-discussed methods.

Fragments can also be chemically synthesized using techniques known in the art such as conventional Merrifield solid phase f-Moc or t-Boc chemistry. For example, peptides of the present invention may be arbitrarily divided into fragments of desired length with no overlap of the fragments, or divided into overlapping fragments of a desired length.

Alteration of Nucleic Acids and Polypeptides: Random Methods Amino acid sequence variants of a protein can be prepared by random mutagenesis of DNA which encodes a protein or a particular domain or region of a protein. Useful methods include PCR mutagenesis and saturation mutagenesis. A ib ofrandom amino acid uence variants can also begenerated by the synthesis of a set of degenerate oligonucleotide sequences. (Methods for screening proteins in a library of variants are elsewhere herein).

PCR Mutagenesis In PCR mutagenesis, reduced Taq polymerase fidelity is used to introduce random mutations into a cloned fragment of DNA (Leung et al., 1989, Technique 1:11- The DNA region to be mutagenized is amplified using the polymerase chain reaction (PCR) under conditions that reduce the fidelity of DNA synthesis by Taq DNA polymerase, by using a dGTP/dATP ratio of five and adding Mn 2 to the PCR reaction. The pool of amplified DNA fragments are inserted into appropriate cloning vectors to provide random mutant libraries.

WO 98/24475 PCTfUS97/22104 -51- Saturation Mutagenesis Saturation mutagenesis allows for the rapid introduction of a large number of single base substitutions into cloned DNA fragments (Mayers et al., 1985, Science 229:242). This technique includes generation of mutations, by chemical treatment or irradiation of single-stranded DNA in vitro, and synthesis of a complimentary DNA strand. The mutation frequency can be modulated by modulating the severity of the treatment, and essentially all possible base substitutions can be obtained. Because this procedure does not involve a genetic selection for mutant fragments both neutral substitutions, as well as those that alter function, are obtained. The distribution of point mutations is not biased toward conserved sequence elements.

Degenerate Olinonucleotides A library of homologs can also be generated from a set of degenerate oligonucleotide sequences. Chemical synthesis of a degenerate sequences can be carried out in an automatic DNA synthesizer, and the synthetic genes then 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 AcidRes. 11:477. Such techniques have been employed 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 U.S. Patents Nos. 5,223,409, 5,198,346, and 5,096,815).

Alteration of Nucleic Acids and Polypeptides: Methods for 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 create variants which include, deletions, insertions, or substitutions, of residues of the known amino acid sequence of a protein. The sites for mutation can be modified individually or in series, by substituting first with conserved Amino acids and then with more radical choices depending upon results achieved, deleting the target residue, or inserting residues of the same or a different class adjacent to the located site, or combinations of options 1-3.

WO 98/24475 PCTIUS97/22104 -52- Alanine Scanning Mutagenesis Alanine scanning mutagenesis is a useful method for identification of certain residues or regions of the desired protein that are preferred locations or domains for mutagenesis, Cunningham and Wells (Science 244:1081-1085, 1989). In alanine scanning, a residue or group of target residues are identified charged residues such as Arg, Asp, His, Lys, and Glu) and replaced by a neutral or negatively charged amino acid (most preferably alanine or polyalanine). Replacement of an amino acid can affect the interaction of the amino acids with the surrounding aqueous environment in or outside the cell. Those domains demonstrating functional sensitivity to the substitutions are then refined by introducing further or other variants at or for the sites of substitution.

Thus, while the site for introducing an amino acid sequence variation is predetermined, the nature of the mutation per se need not be predetermined. For example, to optimize the performance of a mutation at a given site, alanine scanning or random mutagenesis may be conducted at the target codon or region and the expressed desired protein subunit variants are screened for the optimal combination of desired activity.

Oligonucleotide-Mediated Mutagenesis Oligonucleotide-mediated mutagenesis is a useful method for preparing substitution, deletion, and insertion variants of DNA, see, Adelman et al., (DNA 2:183, 1983). Briefly, the desired DNA is altered by hybridizing an oligonucleotide encoding a mutation to a DNA template, where the template is the single-stranded form of a plasmid or bacteriophage containing the unaltered or native DNA sequence of the desired protein. After hybridization, a DNA polymerase is used to synthesize an entire second complementary strand of the template that will thus incorporate the oligonucleotide primer, and will code for the selected alteration in the desired protein DNA. Generally, oligonucleotides of at least 25 nucleotides in length are used. An optimal oligonucleotide will have 12 to 15 nucleotides that are completely complementary to the template on either side of the nucleotide(s) coding for the mutation. This ensures that the oligonucleotide will hybridize properly to the singlestranded DNA template molecule. The oligonucleotides are readily synthesized using techniques known in the art such as th it described by Crea et al. (Proc. Natl. Acad. Sci.

USA, 75: 5765[1978]).

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) which includes the protein subunit DNA to be mutated. The WO 98/24475 PCT/US97/22104 -53 codon(s) in the protein subunit DNA to be mutated are identified. There must be a unique restriction endonuclease site on each side of the identified mutation site(s). If no such restriction sites exist, they may be generated using the above-described oligonucleotide-mediated mutagenesis method to introduce them at appropriate locations in the desired protein subunit DNA. After the restriction sites have been introduced into the plasmid, the plasmid is cut at these sites to linearize it. A double-stranded oligonucleotide encoding the sequence of the DNA 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. This double-stranded oligonucleotide is referred to as the cassette. This cassette is designed to have 3' and 5' ends that are comparable with the ends of the linearized plasmid, such that it can be directly ligated to the plasmid. This plasmid now contains the mutated desired protein subunit DNA sequence.

Combinatorial Mutagenesis Combinatorial mutagenesis can also be used to generate mutants (Ladner et al., WO 88/06630). In this method, the amino acid sequences for a group of homologs or other related proteins are aligned, preferably to promote the highest homology possible.

All of the amino acids which appear at a given position of the aligned sequences can be selected to create a degenerate set of combinatorial sequences. The variegated library of variants is generated by combinatorial mutagenesis at the nucleic acid level, and is encoded by a variegated gene library. For example, a mixture of synthetic oligonucleotides can be enzymatically ligated into gene sequences such that the degenerate set of potential sequences are expressible as individual peptides, or alternatively, as a set of larger fusion proteins containing the set of degenerate sequences.

Other Modifications of H. pylori Nucleic Acids and Polypeptides It is possible to modify the structure of an H. pylori polypeptide for such purposes as increasing solubility, enhancing stability shelf life ex vivo and resistar ce to proteolytic degradation in vivo). A modified H. pylori protein or peptide can be produced in which the amino acid sequence has been altered, such as by amino acid substitution, deletion, or addition as described herein.

An H. pylori peptide can also be modified by substitution of cysteine residues preferably with alanine, serine, threonine, leucine or glutamic acid residues to minimize dimerization via disulfide linkages. In addition, amino acid side chains of fragments of WO 98/24475 PCTIUJS97/22104 -54the protein of the invention can be chemically modified. Another modification is cyclization of the peptide.

In order to enhance stability and/or reactivity, an H. pylori polypeptide can be modified to incorporate one or more polymorphisms in the amino acid sequence of the protein resulting from any natural allelic variation. Additionally, D-amino acids, nonnatural amino acids, or non-amino acid analogs can be substituted or added to produce a modified protein within the scope of this invention. Furthermore, an H. pylori polypeptide can be modified using polyethylene glycol (PEG) according to the method of A. Sehon and co-workers (Wie et al., supra) to produce a protein conjugated with PEG. In addition, PEG can be added during chemical synthesis of the protein. 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 to an appropriate carrier (Mishell and Shiigi, eds, Selected Methods in Cellular Immunology, WH Freeman, San Francisco, CA (1980), U.S. Patent 4,939,239; or mild formalin treatment (Marsh, (1971) Int. Arch. of Allergy and Appl. Immunol., 41: 199 215).

To facilitate purification and potentially increase solubility of an 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 the protein for purification by immobilized metal ion affinity chromatography (Hochuli, E. et al., (1988) Bio/Technology, 6: 1321 1325). In addition, to facilitate isolation ofpeptides free of irrelevant sequences, specific endoprotease cleavage sites can be introduced between the sequences of the fusion moiety and the peptide.

To potentially aid proper antigen processing of epitopes within an H. pylori polypeptide, canonical protease sensitive sites can be engineered between regions, each comprising at least one epitope via recombinant or synthetic methods. For example, charged amino acid pairs, such as KK or RR, can be introduced between regions within a protein or fragment during recombinant construction thereof. The resulting peptide can be rendered sensitive to cleavage by cathepsin and/or other trypsin-like enzymes which would generate portions of the protein containing one or more epitopes. In addition, such charged amino acid residues can result in an increase in the solubility of the peptide.

Primary Methods for Screening Polypeptides and Analogs Various techniques are known in the art for screening generated mutant gene products. Techniques for screening large gene libraries often include cloning the gene library into replicable expression vectors, transforming appropriate cells with the WO 98/24475 PCT/US97/22104 resulting library of vectors, and expressing the genes under conditions in which detection of a desired activity, in this case, binding to H. pylori polypeptide or an interacting protein, facilitates relatively easy isolation of the vector encoding the gene whose product was detected. Each of the techniques described below is amenable to high through-put analysis for screening large numbers of sequences created, by random mutagenesis techniques.

Two Hybrid Systems Two hybrid assays such as the system described above (as with the other screening methods described herein), can be used to identify polypeptides, e.g., fragments or analogs of a naturally-occurring H. pylori polypeptide, of cellular proteins, or of randomly generated polypeptides which bind to an H. pylori protein.

(The H. pylori domain is used as the bait protein and the library of variants are expressed as fish fusion proteins.) In an analogous fashion, a two hybrid assay (as with the other screening methods described herein), can be used to find polypeptides which bind a H.

pylori polypeptide.

Display Libraries In one approach to screening assays, the candidate peptides are displayed on the surface of a cell or viral particle, and the ability of particular cells or viral particles to bind an appropriate receptor protein via the displayed product is detected in a "panning assay". For example, the gene library can be cloned into the gene for a surface membrane protein of a bacterial cell, and the resulting fusion protein detected by panning (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 fashion, a detectably labeled ligand can be used to score for potentially functional peptide homologs. Fluorescently labeled ligands, receptors, can be used to detect homologs which retain ligandbinding activity. The use offluorescently labeled ligands, allows cells to be visually inspected and separated under a fluorescence microscope, or, where the morphology of the cell permits, to be separated by a fluorescence-activated cell sorter.

A gene library can be expressed as a fusion prote;n r n the surface of a viral particle. For instance, in the filamentous phage system, foreign peptide sequences can be expressed on the surface of infectious phage, thereby conferring two significant benefits. First, since these phage can be applied to affinity matrices at concentrations well over 1013 phage per milliliter, a large number of phage can be screened at one time.

Second, since each infectious phage displays a gene product on its surface, if a particular phage is recovered from an affinity matrix in low yield, the phage can be amplified by WO 98/24475 PCTIS97/22104 -56another round of infection. The group of almost identical E. coli filamentous phages M13, fd., and fl are most often used in phage display libraries. Either of the phage gill or gVIII coat proteins can be used to generate fusion proteins without disrupting the ultimate packaging of the viral particle. Foreign epitopes can be expressed at the NH 2 terminal end of pill and phage bearing such epitopes recovered from a large excess of phage lacking this epitope (Ladner et al. PCT publication WO 90/02909; Garrard et al., PCT publication WO 92/09690; Marks et al. (1992) J. Biol. Chem. 267:16007-16010; Griffiths et al. (1993) EMBO J 12:725-734; Clackson et al. (1991) Nature 352:624-628; and Barbas et al. (1992) PNAS 89:4457-4461).

A common approach uses the maltose receptor of E. coli (the outer membrane protein, LamB) as a peptide fusion partner (Charbit et al. (1986) EMBO 5, 3029-3037).

Oligonucleotides have been inserted into plasmids encoding the LamB gene to produce peptides fused into one of the extracellular loops of the protein. These peptides are available for binding to ligands, to antibodies, and can elicit an immune response when the cells are administered to animals. Other cell surface proteins, OmpA (Schorr et al. (1991) Vaccines 91, pp. 387-392), PhoE (Agterberg, et al. (1990) Gene 88, 37-45), and PAL (Fuchs et al. (1991) Bio/Tech 9, 1369-1372), as well as large bacterial surface structures have served as vehicles for peptide display. Peptides can be fused to pilin, a protein which polymerizes to form the pilus-a conduit for interbacterial exchange of genetic information (Thiry et al. (1989) Appl. Environ. Microbiol. 55, 984-993).

Because of its role in interacting with other cells, the pilus provides a useful support for the presentation of peptides to the extracellular environment. Another large surface structure used for peptide display is the bacterial motive organ, the flagellum. Fusion of peptides to the subunit protein flagellin offers a dense array of many peptide copies on the host cells (Kuwajima et al. (1988) Bio/Tech. 6, 1080-1083). Surface proteins of other bacterial species have also served as peptide fusion partners. Examples include the Staphylococcus protein A and the outer membrane IgA protease ofNeisseria (Hansson et al. (1992) J. Bacteriol. 174, 4239-4245 and Klauser et al. (1990) EMBOJ. 9, 1991- 1999).

In the filamentous phage systems and the LamB system described above, the physical link between the ner tide and its encoding DNA occurs by the containment of the DNA within a particle (cell or phage) that carries the peptide on its surface.

Capturing the peptide captures the particle and the DNA within. An alternative scheme uses the DNA-binding protein LacI to form a link between peptide and DNA (Cull et al.

(1992) PNAS USA 89:1865-1869). This system uses a plasmid containing the LacI gene with an oligonucleotide cloning site at its 3'-end. Under the controlled induction by arabinose, a LacI-peptide fusion protein is produced. This fusion retains the natural WO 98/24475 PCT/US97/22104 -57ability of LacI to bind to a short DNA sequence known as LacO operator (LacO). By installing two copies of LacO on the expression plasmid, the Lacl-peptide fusion binds tightly to the plasmid that encoded it. Because the plasmids in each cell contain only a single oligonucleotide sequence and each cell expresses only a single peptide sequence, the peptides become specifically and stably associated with the DNA sequence that directed its synthesis. The cells of the library are gently lysed and the peptide-DNA complexes are exposed to a matrix of immobilized receptor to recover the complexes containing active peptides. The associated plasmid DNA is then reintroduced into cells for amplification and DNA sequencing to determine the identity of the peptide ligands.

As a demonstration of the practical utility of the method, a large random library of dodecapeptides was made and selected on a monoclonal antibody raised against the opioid peptide dynorphin.B. A cohort of peptides was recovered, all related by a consensus sequence corresponding to a six-residue portion of dynorphin B. (Cull et al.

(1992) Proc. Natl. Acad. Sci. U.S.A. 89-1869) This scheme, sometimes referred to as peptides-on-plasmids, differs in two important ways from the phage display methods. First, the peptides are attached to the C-terminus of the fusion protein, resulting in the display of the library members as peptides having free carboxy termini. Both of the filamentous phage coat proteins, pIll and pVIII, are anchored to the phage through their C-termini, and the guest peptides are placed into the outward-extending N-terminal domains. In some designs, the phagedisplayed peptides are presented right at the amino terminus of the fusion protein.

(Cwirla, et al. (1990) Proc. Natl. Acad Sci. U.S.A. 87, 6378-6382) A second difference is the set of biological biases affecting the population of peptides actually present in the libraries. The LacI fusion molecules are confined to the cytoplasm of the host cells.

The phage coat fusions are exposed briefly to the cytoplasm during translation but are rapidly secreted through the inner membrane into the periplasmic compartment, remaining anchored in the membrane by their C-terminal hydrophobic domains, with the N-termini, containing the peptides, protruding into the periplasm while awaiting assembly into phage particles. The peptides in the Lad and phage libraries may differ significantly as a result of their exposure to different proteolytic activities. The phage coat proteins require transport across the inner membrane and signal peptidase processing as a prelude to incorporation into phage. Certain peptides exert a deleterious effect on these processes and are underrepresented in the libraries (Gallop et al. (1994) J.

Med. Chem. 37(9):1233-1251). These particular biases are not a factor in the LacI display system.

The number of small peptides available in recombinant random libraries is enormous. Libraries of 107-109 independent clones are routinely prepared. Libraries as WO 98/24475 PCTfUS97/22104 -58large as 1011 recombinants have been created, but this size approaches the practical limit for clone libraries. This limitation in library size occurs at the step of transforming the DNA containing randomized segments into the host bacterial cells. To circumvent this limitation, an in vitro system based on the display of nascent peptides in polysome complexes has recently been developed. This.display library method has the potential of producing libraries 3-6 orders of magnitude larger than the currently available phage/phagemid or plasmid libraries. Furthermore, the construction of the libraries, expression of the peptides, and screening, is done in an entirely cell-free format.

In one application of this method (Gallop et al. (1994) J. Med. Chem.

37(9):1233-1251), a molecular DNA library encoding 1012 decapeptides was constructed and the library expressed in an E. coli S30 in vitro coupled transcription/translation system. Conditions were chosen to stall the ribosomes on the mRNA, causing the accumulation of a substantial proportion of the RNA in polysomes and yielding complexes containing nascent peptides still linked to their encoding RNA.

The polysomes are sufficiently robust to be affinity purified on immobilized receptors in much the same way as the more conventional recombinant peptide display libraries are screened. RNA from the bound complexes is recovered, converted to cDNA, and amplified by PCR to produce a template for the next round of synthesis and screening.

The polysome display method can be coupled to the phage display system. Following several rounds of screening, cDNA from the enriched pool of polysomes was cloned into a phagemid vector. This vector serves as both a peptide expression vector, displaying peptides fused to the coat proteins, and as a DNA sequencing vector for peptide identification. By expressing the polysome-derived peptides on phage, one can either continue the affinity selection procedure in this format or assay the peptides on individual clones for binding activity in a phage ELISA, or for binding specificity in a completion phage ELISA (Barret, et al. (1992) Anal. Biochem 204,357-364). To identify the sequences of the active peptides one sequences the DNA produced by the phagemid host.

Secondary Screening of Polvpeptides and Analogs The high through-put assays described above can be followed by secondar/ screens in order to identify further biological activities which will, allow one skilled in the art to differentiate agonists from antagonists. The type of a secondary screen used will depend on the desired activity that needs to be tested. For example, an assay can be developed in which the ability to inhibit an interaction between a protein of interest and its respective ligand can be used to identify antagonists from a group of peptide fragments isolated though one of the primary screens described above.

WO 98/24475 PCT/US97/22104 -59- Therefore, methods for generating fragments and analogs and testing them for activity are known in the art. Once the core sequence of interest is identified, it is routine for one skilled in the art to obtain analogs and fragments.

Peptide Mimetics ofH. pylori Polypeptides The invention also provides for reduction of the protein binding domains of the subject H. pylori polypeptides to generate mimetics, e.g. peptide or non-peptide agents.

The peptide mimetics are able to disrupt binding of a polypeptide to its counter ligand, in the case of an H pylori polypeptide binding to a naturally occurring ligand. The critical residues of a subject H. pylori polypeptide which are involved in molecular recognition of a polypeptide can be determined and used to generate H. pylori-derived peptidomimetics which competitively or noncompetitively inhibit binding of the H pylori polypeptide with an interacting polypeptide (see, for example, European patent applications EP-412,762A and EP-B31,080A).

For example, scanning mutagenesis can be used to map the amino acid residues of a particular H. pylori polypeptide involved in binding an interacting polypeptide, peptidomimetic compounds diazepine or isoquinoline derivatives) can be generated which mimic those residues in binding to an interacting polypeptide, and which therefore can inhibit binding of an H. pylori polypeptide to an interacting polypeptide and thereby interfere with the function ofH. pylori polypeptide. For instance, nonhydrolyzable peptide analogs of such residues can be generated using benzodiazepine see Freidinger et al. in Peptides.: Chemistry and Biology, G.R. Marshall ed., ESCOM Publisher: Leiden, Netherlands, 1988), azepine see Huffman et al. in Peptides: Chemistry and Biology, G.R. Marshall ed., ESCOM Publisher: Leiden, Netherlands, 1988), substituted gama lactam rings (Garvey ct al. in Peptides: Chemistry and Biology, G.R. Marshall ed., ESCOM Publisher: Leiden, Netherlands, 1988), ketomethylene 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), p-turn dipeptide cores (Nagai et al. (1985) Tetrahedron Lett 26:647; and Sato et al. (1986) J Chem Soc Perkin Trans 1:1231), and p-aminoalcohols (Gordon et al. (1085) Biochem Biophys Res Commun 126:419; and Dann et al. (1986) Biochem Biophys Res Commun 134:71).

VI. Vaccine Formulations for H. pylori Nucleic Acids and Polvpeptides This invention also features vaccine compositions or formulations (used interchangeably herein) for protection against infection by H. pylori or for treatment of H. pylori infection. As used herein, the term "treatment of H. pylori infection" refers to WO 98/24475 PCT/UIJS97/22104 therapeutic treatment of an existing or established H. pylori infection. The terms "protection against H. pylori infection" or "prophylactic treatment" refer to the use ofH.

pylori vaccine formulation for reducing the risk of or preventing an infection in a subject at risk for H. pylori infection. In one embodiment, the vaccine compositions contain one or more immunogenic components, such as a surface protein, from H. pylori, or portion thereof, and a pharmaceutically acceptable carrier. For example, in one embodiment, the vaccine formulations of the invention contain at least one or combination of H. pyiori polypeptides or fragments thereof, from same or different H. pylori antigens. Nucleic acids and H. pylori polypeptides for use in the vaccine formulations of the invention include the nucleic acids and polypeptides set forth in the Sequence Listing, preferably those H. pylori nucleic acids that encode surface proteins and surface proteins or fragments thereof. For example, a preferred nucleic acid and H. pylori polypeptide for use in a vaccine composition of the invention is selected from the group of nucleic acids which encode cell envelope proteins and H. pylori cell envelope proteins as set forth in Table 1. However, any nucleic acid encoding an immunogenic H. pylori protein and H.

pylori polypetide, or portion thereof, can be used in the present invention. These vaccines have therapeutic and/or prophylactic utilities.

One aspect of the invention provides a vaccine composition for protection against infection by H. pylori which contains at least one immunogenic fragment of an H. pylori protein and a pharmaceutically acceptable carrier. Preferred fragments include peptides of at least about 10 amino acid residues in length, preferably about 10-20 amino acid residues in length, and more preferably about 12-16 amino acid residues in length.

Immunogenic components of the invention can be obtained, for example, by screening polypeptides recombinantly produced from the corresponding fragment of the nucleic acid encoding th full-length H. protein. In addition, fragments can be chemically synthesized using techniques known in the art such as conventional Merrifield solid phase f-Moc or t-Boc chemistry.

In one embodiment, immunogenic components are identified by the ability of the peptide to stimulate T cells. Peptides which stimulate T cells, as determined by, for example, T cell proliferation or cytokine secretion are defined herein as comprising at least one T cell enitcpe. T cell epitopes are believed to be involved in initiation and perpetuation of the immune response to the protein allergen which is responsible for the clinical symptoms of allergy. These T cell epitopes are thought to trigger early events at the level of the T helper cell by binding to an appropriate HLA molecule on the surface of an antigen presenting cell, thereby stimulating the T cell subpopulation with the relevant T cell receptor for the epitope. These events lead to T cell proliferation, lymphokine secretion, local inflammatory reactions, recruitment of additional immune WO 98/24475 PCT/US97/22104 -61 cells to the site of antigen/T cell interaction, and activation of the B cell cascade, leading to the production of antibodies. A T cell epitope is the basic element, or smallest unit of recognition by a T cell receptor, where the epitope comprises amino acids essential to receptor recognition approximately 6 or 7 amino acid residues). Amino acid sequences which mimic those of the T cell epitopes are within the scope of this invention.

In another embodiment, immunogenic components of the invention are identified through genomic vaccination. The basic protocol is based on the idea that expression libraries consisting of all or parts of a pathogen genome, an H. pylori genome, can confer protection when used to genetically immunize a host. This expression library immunization (ELI) is analogous to expression cloning and involves reducing a genomic expression library of a pathogen, H. pylori, into plasmids that can act as genetic vaccines. The plasmids can also be designed to encode genetic adjuvants which can dramatically stimulate the humoral response. These genetic adjuvants can be introduced at remote sites and act as well extracelluraly as intracellularly.

This is a new approach to vaccine production that has many of the advantages of live/attenuated pathogens but no risk of infection. An expression library of pathogen DNA is used to immunize a host thereby producing the effects of antigen presentation of a live vaccine without the risk. For example, in the present invention, random fragments from the H. pylori genome or from cosmid or plasmid clones, as well as PCR products from genes identified by genomic sequencing, can be used to immunize a host. The feasibility of this approach has been demonstrated with Mycoplasmapulmonis (Barry et al., Nature 377:632-635, 1995), where even partial expression libraries of Mycoplasma pulmonis, a natural pathogen in rodents, provided protection against challenge from the pathogen.

ELI is a technique that allows for production of a non-infectious multipartite vaccine, even when little is known about pathogen's biology, because ELI uses the immune system to screen candidate genes. Once isolated, these genes can be used as genetic vaccines or for development of recombinant protein vaccines. Thus, ELI allows for production of vaccines in a systematic, largely mechanized fashion.

Screening immunogenic components can be accomplished using one or more of several different assays. For example, in vitro, peptide T cell stimulatory activity is assayed by contacting a peptide known or suspected of being immunogenic with an antigen presenting cell which presents appropriate MHC molecules in a T cell culture.

Presentation of an immunogenic H. pylori peptide in association with appropriate MHC molecules to T cells in conjunction with the necessary costimulation has the effect of transmitting a signal to the T cell that induces the production of increased levels of WO 98/24475 PCTIS97/22104 62 cytokines, particularly of interleukin-2 and interleukin-4. The culture supernatant can be obtained and assayed for interleukin-2 or other known cytokines. For example, any one of several conventional assays for interleukin-2 can be employed, such as the assay described in Proc. Natl. Acad. Sci USA, 86: 1333 (1989) the pertinent portions of which are incorporated herein by reference. A kit for an assay for the production of interferon is also available from Genzyme Corporation (Cambridge, MA).

Alternatively, a common assay for T cell proliferation entails measuring tritiated thymidine incorporation. The proliferation of T cells can be measured in vitro by determining the amount of 3 H-labeled thymidine incorporated into the replicating DNA of cultured cells. Therefore, the rate of DNA synthesis and, in turn, the rate of cell division can be quantified.

Vaccine compositions or formulations of the invention containing one or more immunogenic components H. pylori polypeptide or fragment thereof or nucleic acid encoding an H. pylori polypeptide or fragment thereof) preferably include a pharmaceutically acceptable carrier. The term "pharmaceutically acceptable carrier" is intended to include any and all solvents, dispersion media, coatings, antibacterial and antifungal agents, isotonic and absorption delaying agents, and the like, 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 auxiliary substances such as wetting or emulsifying agents, preservatives or buffers, which enhance the shelf life or effectiveness of the H. pylori nucleic acid or polypeptide. For vaccine formulations of the invention containing H. pylori polypeptides, the polypeptide is preferably coadministered with a suitable adjuvant and/or a delivery system described herein.

It will be apparent to those of skill in the art that the therapeutically effective amount of DNA or protein of this invention will depend, inter alia, upon the administration schedule, the unit dose of an H. pylori nucleic acid or polypeptide administered, whether the protein or nucleic acid is administered in combination with other therapeutic agents, the immune status and health of the patient, and the therapeutic activity of the particular protein or nucleic acid.

Vaccine formulations are conventionally administered parenterally, by injection, either subcutaneously or intramuscularly. Methods for intramuscular immunization are described by Wolff et al. (1990) Science 247: 1465-1468 and by Sedegah et al. (1994) Immunology 91: 9866-9870. Other modes of administration include oral and pulmonary formulations, suppositories, and transdermal applications.

Oral immunization is preferred over parenteral methods for inducing protection against WO 98/24475 PCT/US97/22104 -63infection by H. pylori. Czinn et. al. (1993) Vaccine 11: 637-642. Oral formulations include such normally employed excipients as, for example, pharmaceutical grades of mannitol, lactose, starch, magnesium stearate, sodium saccharine, cellulose, magnesium carbonate, and the like.

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

In another embodiment, the vaccine formulation includes, as a pharmaceutically acceptable carrier, a delivery system. Suitable delivery systems for use in the vaccine formulations of the invention include biodegradable microcapsules or immunostimulating complexes (ISCOMs), cochleates, or liposomes, genetically engineered attenuated live vectors such as viruses or bacteria, and recombinant (chimeric) virus-like particles, bluetongue. In another embodiment of the invention, the vaccine formulation includes both a delivery system and an adjuvant.

Delivery systems in humans may include enteric release capsules protecting the antigen from the acidic environment of the stomach, and including H. pylori polypeptide in an insoluble form as fusion proteins. Suitable carriers for the vaccines of the invention are enteric coated capsules and polylactide-glycolide microspheres. Suitable diluents are 0.2 N NaHCO3 and/or saline.

Vaccines of the invention can be administered as a primary prophylactic agent in adults or in children, as a secondary prevention, after successful eradication ofH. pylori in an infected host, or as a therapeutic agent in the aim to induce an immune response in a susceptible host to prevent infection by H. pylori. The vaccines of the invention are administered in amounts readily determined by persons of ordinary skill in the art.

Thus, for adults a suitable dosage will be in the range of 10 ug to 10 g, preferably 10 jg WO 98/24475 PCT/US97/22104 -64to 100 mg, for example 50 pg to 50 mg. A suitable dosage for adults will also be in the range of 5 lpg to 500 mg. Similar dosage ranges will be applicable for children.

The amount of adjuvant employed 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 5 pg to 50 pg, for example 10 pg to 35 pg. When used in the form of microcapsules, the amount used will depend on the amount employed in the matrix of the microcapsule to achieve the desired dosage. The determination of this amount is within the skill of a person of ordinary skill in the art.

Those skilled in the art will recognize that the optimal dose may be more or less depending upon the patient's body weight, disease, the route of administration, and other factors. Those skilled in the art will.also recognize that appropriate dosage levels can be obtained based on results with known oral vaccines such as, for example, a vaccine based on an E. coli lysate (6 mg dose daily up to total of 540 mg) and with an enterotoxigenic E. coli purified antigen (4 doses of I mg) (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 upon the disease, the formulation, and efficacy data from clinical trials. Without intending any limitation as to the course of treatment, the treatment can be administered over 3 to 8 doses for a primary immunization schedule over 1 month (Boedeker, American Gastroenterological Assoc.

888:A-222 (1993)).

In a preferred embodiment, a vaccine composition of the invention can be based on a killed whole E. coli preparation with an immunogenic fragment of an H. pylori protein of the invention expressed on its surface or it can be based on an E. coli lysate, wherein the killed E. coli acts as a carrier or an adjuvant.

It will be apparent to those skilled in the art that some of the vaccine compositions of the invention are useful only for preventing H. pylori infection, some are useful only for treating H. pylori infection, and some are useful for both preventing and treating 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 should be understood that amelioratio.i of any of the symptoms of H. pylori infection is a desirable clinical goal, including a lessening of the dosage of medication used to treat H. pylori-caused disease, or an increase in the production of antibodies in the serum or mucous of patients.

WO 98/24475 PCT/US97/22104 VII. Antibodies Reactive With H. pylori Polypeptides The invention also includes antibodies specifically reactive with the subject H pylori polypeptide. Anti-protein/anti-peptide antisera or monoclonal antibodies can be made by standard protocols (See, for example, Antibodies: A Laboratory Manual ed. by Harlow and Lane (Cold Spring Harbor Press: 1988)). A mammal such as a mouse, a hamster or rabbit can be immunized with an immunogenic form of the peptide.

Techniques for conferring immunogenicity on a protein or peptide include conjugation to carriers or other techniques well known in the art. An immunogenic portion of the subject H. pylori polypeptide can be administered in the presence of adjuvant. The progress of immunization can be monitored by. detection of antibody titers in plasma or serum. Standard ELISA or other immunoassays can be used with the immunogen as antigen to assess the levels of antibodies.

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

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

Both monoclonal and polyclonal antibodies (Ab) directed against H. pylori polypeptides or H. pylori polypeptide variants, and antibody fragments such as Fab' and F(ab')2, can be used to block the action ofH. pylori polypeptide and allow the study of the role of a particular H. pylori polypeptide of the invention in aberrant or unwanted WO 98/24475 PCT/US97/22104 -66intracellular signaling, as well as the normal cellular function of the H. pylori and by microinjection of anti-H. pylori polypeptide antibodies of the present invention.

Antibodies which specifically bind H. pylori epitopes can also be used in immunohistochemical staining of tissue samples in order to evaluate the abundance and pattern of expression of H. pylori antigens. Anti H. pylori polypeptide antibodies can be used diagnostically in immuno-precipitation and immuno-blotting to detect and evaluate H. pylori levels in tissue or bodily fluid as part of a clinical testing procedure. Likewise, the ability to monitor H. pylori polypeptide levels in an individual can allow determination of the efficacy of a given treatment regimen for an individual afflicted with such a disorder. The level of an H. pyloripolypeptide can be measured in cells found in bodily fluid, such as in urine samples or can be measured in tissue, such as produced by gastric biopsy. Diagnostic assays using anti-H. pylori antibodies can include, for example, immunoassays designed to aid in early diagnosis of H. pylori infections. The present invention can also be used as a method of detecting antibodies contained in samples from individuals infected by this bacterium using specific H. pylori antigens.

Another application of anti-H. pylori polypeptide antibodies of the invention is in the immunological screening ofcDNA libraries constructed in expression vectors such as Xgtl 1, gtl8-23, XZAP, and XORF8. Messenger libraries of this type, having coding sequences inserted in the correct reading frame and orientation, can produce fusion proteins. For instance, Xgtl will produce fusion proteins whose amino termini consist of B-galactosidase amino acid sequences and whose carboxy termini consist of a foreign polypeptide. Antigenic epitopes of a subject H. pylori polypeptide can then be detected with antibodies, as, for example, reacting nitrocellulose filters lifted from infected plates with anti-H. pylori polypeptide antibodies. Phage, scored by this assay, can then be isolated from the infected plate. Thus, the presence ofH. pylori gene homologs can be detected and cloned from other species, and alternate isoforms (including splicing variants) can be detected and cloned.

VIII. Kits Containing Nucleic Acids, Polypeptides or Antibodies of the Invention The nucleic acid, polypeptides and antibodies of the invention can be combined with other reagents and articles to form kits. Kits for diagnostic purposes typically comprise the nucleic acid, polypeptides or antibodies in vials or other suitable vessels.

Kits typically comprise other reagents for performing hybridization reactions, polymerase chain reactions (PCR), or for reconstitution of lyophilized components, such as aqueous media, salts, buffers, and the like. Kits may also comprise reagents for sample processing such as detergents, chaotropic salts and the like. Kits may also WO 98/24475 PCTfUS97/22104 -67comprise immobilization means such as particles, supports, wells, dipsticks and the like.

Kits may also comprise labeling means such as dyes, developing reagents, radioisotopes, fluorescent agents, luminescent or chemiluminescent agents, enzymes, intercalating agents and the like. With the nucleic acid and amino acid sequence information provided herein, individuals skilled in art can readily assemble kits to serve their particular purpose. Kits further can include instructions for use.

IX. Drug Screening Assays Using H pylori Polypeptides By making available purified and recombinant H. pylori polypeptides, the present invention provides assays which can be used to screen for drugs which are either agonists or antagonists of the normal cellular function, in this case, of the subject H.

pylori polypeptides, or of their role in intracellular signaling. Such inhibitors or potentiators may be useful as new therapeutic agents to combat H. pylori infections in humans. A variety of assay formats will suffice and, in light of the present inventions, will be comprehended by the skilled artisan.

In many drug screening programs which test libraries of compounds and natural extracts, high throughput assays are desirable in order to maximize the number of compounds surveyed in a given period of time. Assays which are performed in cell-free systems, such as may be derived with purified or semi-purified proteins, are often preferred as "primary" screens in that they can be generated to permit rapid development and relatively easy detection of an alteration in a molecular target which is mediated by a test compound. Moreover, the effects of cellular toxicity and/or bioavailability of the test compound can be generally ignored in the in vitro system, the assay instead being focused primarily on the effect of the drug on the molecular target as may be manifest in an alteration of binding affinity with other proteins or change in enzymatic properties of the molecular target. Accordingly, in an exemplary screening assay of the present invention, the compound of interest is contacted with an isolated and purified H. pylori polypeptide.

Screening assays can be constructed in vitro with a purified H. pylori polypeptide or fragment thereof, such as an H. pylori polypeptide having enzymatic activity, such that the activity of .he polypeptide produces a detectable reaction product.

The efficacy of the compound can be assessed by generating dose response curves from data obtained using various concentrations of the test compound. Moreover, a control assay can also be performed to provide a baseline for comparison. Suitable products include those with distinctive absorption, fluorescence, or chemi-luminescence properties, for example, because detection may be easily automated. A variety of synthetic or naturally occurring compounds Can be tested in the assay to identify those WO 98/24475 PCT[US97/22104 -68which inhibit or potentiate the activity of the H. pylori polypeptide. Some of these active compounds may directly, or with chemical alterations to promote membrane permeability or solubility, also inhibit or potentiate the same activity enzymatic activity) in whole, live H. pylori cells.

This invention is further illustrated by the following examples which should not be construed as limiting. The contents of all references and published patent applications cited throughout this application are hereby incorporated by reference.

EXEMPLIFICATION

I. Cloning and Sequencing of H. pylori DNA H. pylori chromosomal DNA was isolated according to a basic DNA protocol outlined in Schleif R.F. and Wensink Practical Methods in Molecular Biology, p.98, Springer-Verlag, NY., 1981, with minor 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-laurylsarcosine) was added. Suspension was chilled and ammonium acetate (NH 4 Ac) was added to final concentration of 2.0 M. DNA was extracted, first with chloroform, then with phenolchloroform, and reextracted with chloroform. DNA was precipitated with isopropanol, washed twice with 70% EtOH, dried and resuspended in TE.

Following isolation whole genomic H. pylori DNA was nebulized (Bodenteich et al., Automated DNA Sequencing and Analysis Venter, Academic Press, 1994) to a median size of 2000 bp. After nebulization, the DNA was concentrated and separated on a standard 1% agarose gel. Several fractions, corresponding to approximate sizes 900-1300 bp, 1300-1700 bp, 1700-2200 bp, 2200-2700 bp, were excised from the gel and purified by the GeneClean procedure (BiolOl, Inc.).

The purified DNA fragments were then blunt-ended using T4 DNA polymerase.

The healed DNA was then ligated to unique BstXI-linker adapters in 100-1000 fold molar excess. These linkers are complimentary to the BstXI-cut pMPX vectors, while the overhang is not self-complimentary. Therefore, the linkers will not concatemerize nor will the cut-vector religate itself easily. The linker-adopted inserts were separated from the unincorporated linkers on a 1% agarose gel and purified using GeneClean. The linker-adopted inserts were then ligated to each of the 20 pMPX vectors to construct a series of "shotgun" subclone libraries. The vectors contain an out-of-frame lacZ gene at the cloning site which becomes in-frame in the event that an adapter-dimer is cloned, allowing these to be avoided by their blue-color.

WO 98/24475 PCTIUS97/22104 -69- All subsequent steps were based on the multiplex DNA sequencing protocols outlined in Church G.M. and Kieffer-Higgins Science 240:185-188, 1988. Only major modifications to the protocols are highlighted. Briefly, each of the 20 vectors was then transformed into DH5a competent cells (Gibco/BRL, DH5a transformation protocol). The libraries were assessed by plating onto antibiotic plates containing ampicillin, methicillin and IPTG/Xgal. The plates were incubated overnight at 370C.

Successful transformants were then used for plating of clones and pooling into the multiplex pools. The clones were picked and pooled into 40 ml growth medium cultures. The cultures were grown overnight at 370C. DNA was purified using the Qiagen Midi-prep kits and Tip-100 columns (Qiagen, Inc.). In this manner, 100 pg of DNA was obtained per pool. Fifteen 96-well plates of DNA were generated to obtain a 5-10 fold sequence redundancy assuming 250-300 base average read-lengths.

These purified DNA samples were then sequenced using the multiplex DNA sequencing based on chemical degradation methods (Church G.M. and Kieffer-Higgins Science 240:185-188, 1988) or by Sequithrem (Epicenter Technologies) dideoxy sequencing protocols. The sequencing reactions were electrophoresed and transferred onto nylon membranes by direct transfer electrophoresis from 40 cm gels (Richterich P.

and Church Methods in Enzymology 218:187-222, 1993) or by electroblotting (Church, supra). 24 samples were run per gel. 45 successful membranes were produced by chemical sequencing and 8 were produced by dideoxy sequencing. The DNA was covalently bound to the membranes by exposure to ultraviolet light, and hybridized with labeled oligonucleotides complimentary to tag sequences on the vectors (Church, supra).

The membranes were washed to rinse off non-specifically bound probe, and exposed to X-ray film to visualize individual sequence ladders. After autoradiography, the hybridized probe was removed by incubation at 650 C, and the hybridization cycle repeated with another tag sequence until the membrane had been probed 38 times for chemical sequencing membranes and 10 times for the dideoxy sequencing membranes.

Thus, each gel produced a large number of films, each containing new sequencing information. Whenever a new blot was processed, it was initially probed for an internal standard sequence added to each of the pools.

Digital images of the films were generated using a laser-scanning densitomet;r (Molecular Dynamics, Sunnyvale, CA). The digitized images were processed on computer workstations (VaxStation 4000's) using the program REPLICATM (Church et al., Automated DNA Sequencing and Analysis Venter, Academic Press, 1994).

Image processing included lane straightening, contrast adjustment to smooth out intensity differences, and resolution enhancement by iterative gaussian deconvolution.

The sequences were then automatically picked in REPLICA T M and displayed for WO 98/24475 PCT/US97/22104 interactive proofreading before being stored in a project database. The proofreading was accomplished by a quick visual scan of the film image followed by mouse clicks on the bands of the displayed image to modify the base calls. Many of the sequence errors could be detected and corrected because multiple sequence reads covering the same portion of the genomic DNA provide adequate sequence redundancy for editing. Each sequence automatically received an identification number (corresponding to microtiter plate, probe information, and lane set number). This number serves as a permanent identifier of the sequence so it is always possible to identify the original of any particular sequence without recourse to a specialized database.

Routine assembly ofH. pylori sequences was done using the program FALCON (Church, Church et al., Automated DNA Sequenicng and Analysis Venter, ed.), Academic Press, 1994). This program has proven to be fast and reliable for most sequences. The assembled contigs were displayed using a modified version of GelAssemble, developed by the Genetics Computer Group (GCG) (Devereux et al., Nucleic Acid Res. 12:387-95, 1984) that interacts with REPLICA

TM

This provided for an integrated editor that allows multiple sequence gel images to be instantaneously called up from the REPLICAT' database and displayed to allow rapid scanning of contigs and proofreading of gel traces where discrepancies occurred between different sequence reads 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 powerful gene expression system, the pET System (Novagen), for cloning and expression of recombinant proteins in E. coli, was selected. Also, a DNA sequence encoding a peptide tag, the His-Tag, was fused to the 3' end of DNA sequences of interest in order to facilitate purification of the recombinant protein products. The 3' end was selected for fusion in order to avoid alteration of any terminal signal sequence. The exception to the above was ppiB, a gene cloned for use as a control in the expression studies. In this study, the sequence for H. pylori ppiB contains a DNA sequence encoding a His-Tag fused to the 5' end of the full length gene, because the protein product of this gene does not cont;.in a signal sequence and is expressed as a cytosolic protein.

WO 98/24475 PCT/US97/22104 -71- PCR Amplification and cloning ofDNA sequences containing ORF'sfor membrane and secreted proteins from the J99 Strain of Helicobacter pylori.

Sequences chosen (from the list of the DNA sequences of the invention) for cloning from the J99 strain ofH. pylori were prepared for amplification cloning by polymerase chain reaction (PCR). Synthetic oligonucleotide primers (Table 3) specific for the 5' and 3' ends of open reading frames (ORFs) were designed and purchased (GibcoBRL Life Technologies, Gaithersburg, MD, USA). All forward primers (specific for the 5' end of the sequence) were designed to include an Ncol cloning site at the extreme 5' terminus, except for HpSeq. 4821082 where Ndel was used. These primers were designed to permit initiation of protein translation at a methionine residue followed by a valine residue and the coding sequence for the remainder of the native H pylori DNA sequence. An exception is H. pylori sequence 4821082 where the initiator methionine is immediately followed by the remainder of the native H. pylori DNA sequence. All reverse primers (specific for the 3' end of any H. pylori ORF) included a EcoRI site at the extreme 5' terminus to permit cloning of each H pylori sequence into the reading frame of the pET-28b. The pET-28b vector provides sequence encoding an additional 20 carboxy-terminal amino acids (only 19 amino acids in HpSeq. 26380318 and HpSeq.14640637) including six histidine residues (at the extreme C-terminus), which comprise the His-Tag. An exception to the above, as noted earlier, is the vector construction for the ppiB gene. A synthetic oligonucleotide primer specific for the end of ppiB gene encoded a BamHI site at its extreme 5' terminus and the primer for the 3' end of the ppiB gene encoded a Xhol site at its extreme 5' terminus.

TABLE 3 Oligonucleotide primers used for PCR amplification of H ,lonr DNA sequences Outer membrane Forward primer 5' to 3' Reverse Primer 5' to 3' Proteins Protein 16225006 5'-TATACCATGGTGGG CGCTAA-3' (SEQ ID AGGATTTTTG-3' (SEQ NO:195) ID NO:196) Protein 26054702 5'-TTAACCATGGTGA AAAGCGATA-3' (SEQ ID ACGATCAATC-3' (SEQ NO:197) ID NO:198) Protein 7116626 5'-ATATCCATGGTGA GTTTGATGA-3' (SEQ ID TTTATTTTGCCA-3' NO:199) (SEQ ID NO:200) WO 98/24475 PTU9/20 PCTIUS97/22104 72 Protein 29479681 5'-AATTCCATGGTGG GGGCTATG-3' (SEQ ID AGCCAAAATC-3' (SEQ ID NO:202) Protein 14640637 5'-AATTCCATGGTG CATAACTTCCATT-3' GCATCCAAATGGA-3' ID NO:203) (SEQ ID NO:204) Periplasmic/ Secreted Protein 30100332 5'-ATTTCCATGGTCATG TCTCATATT-3' (SEQ ID TTTTATTCCAC-3' (SEQ ID NO:206) Protein 4721061 5'-AACCATGGTGATTT TAAGCATTGAAAG-3' TCAAAATTTTTTAAC ID NO:207) AG-3' (SEQ ID NO:208) Other Surface Proteins Protein 4821082 5'-GATCATCCATATGTT ATCTTCTAAT-3' (SEQ TTTTAACCCTG-3' NO:209) (SEQ ID NO:2 Protein 978477 5'-TATACCATGGTGAA ATTTTTTCTTTTA-3' GCGTCTTGTAAAAG- (SEQ ID NO:21 1) 3' (SEQ ID NO:2 12) Inner Membrane Protein Protein 26380318 5'-TATACCATGGTGAT GGACAAACTC-3' (SEQ GGGGCGATA-3' (SEQ ID NO:213) ID NO:214) Cytoplasmic Protein U T'i* A r T

A

ppi 50-TTAT GGATCCAAAC 51-TATC-I-A' i 1ui CAATTAAAACT-3' (SEQ GAGAAGGGC-3' (SEQ NO:215) IID NO:216) Genomic DNA prepared from the J99 strain of H pylori (ATCC #55679; deposited by Genome Therapeutics Corporation, 100 Beaver Street, Waltham, MA 02154) was used as the source of template DNA for PCR amplification reactions (Current Protocols in Molecular Biology, John Wiley and Sons, Inc., F. Ausubel et al., eds., 1994). To amplify a DNA sequence containing an H pylori ORF, genomic DNA nanograms) was introduced into a reaction vial containing 2 mM MgCI2, 1 micromolar synthetic oligonucleotide primers (forward and reverse primers) complementary to and flanking a defined H pylori ORF, 0.2 mM of each deoxynucleotide triphosphate; dATP, dGTP, dCTP, dTTP and 2.5 units of heat stable WO 98/24475 PCT/US97/22104 -73- DNA polymerase (Amplitaq, Roche Molecular Systems, Inc., Branchburg, NJ, USA) in a final volume of 100 microliters. 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 26054702, Protein 7116626, Protein 29479681, Protein 30100332, and Protein 4821082; Denaturation at 94 0 C for 2 min, 2 cycles at 94 0 C for 15 sec, 30 0 C for 15 sec and 72 0 C for 1.5 min 23 cycles at 94 0 C for 15 sec, 55 0 C for 15 sec and 72 0 C for 1.5 min Reactions were concluded at 72 0 C for 6 minutes.

Protein 16225006; Denaturation at 94 0 C for 2 min, 25 cycles at 95 0 C for 15 sec, 55 0 C for 15 sec and 72 0 C for 1.5 min Reaction was concluded at 72 0 C for 6 minutes.

Protein 4721061; Denaturation at 94 0 C for 2 min, 2 cycles at 94 0 C for 15 sec, 36 0 C for 15 sec and 72 0 C for 1.5 min 23 cycles at 94 0 C for 15 sec, 60 0 C for 15 sec and 720C for 1.5 min Reactions were concluded at 72 0 C for 6 minutes.

Protein 26380318; Denaturation at 94°C for 2 min, 2 cycles at 94 0 C for 15 sec, 38 0 C for 15 sec and 72 0 C for 1.5 min 23 cycles at 94 0 C for 15 sec, 62 0 C for 15 sec and 72 0 C for 1.5 min Reactions were concluded at 72 0 C for 6 minutes.

Protein 14640637; Denaturation at 94 0 C for 2 min, 2 cycles at 94 0 C for 15 sec, 33 0 C for 15 sec and 720C for 1.5 min cycles at 94 0 C for 15 sec, 55 0 C for 15 sec and 720C for 1.5 min Reactions were concluded at 72 0 C for 6 minutes.

WO 98/24475 PCTI/US97/22104 -74- Conditions for amplification ofH. pylori ppiB; Denaturation at 94 0 C for 2 min, 2 cycles at 94 0 C for 15 sec, 32 0 C for 15 sec and 72 0 C for 1.5 min cycles at 94 0 C for 15 sec, 56 0 C for 15 sec and 72 0 C for 1.5 min Reactions were concluded at 72 0 C for 6 minutes Upon completion of thermal cycling reactions, each sample of amplified DNA was washed and purified using the Qiaquick Spin PCR purification kit (Qiagen, Gaithersburg, MD, USA). All amplified DNA samples were subjected to digestion with the restriction endonucleases, Ncol 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 Molecular Biology, John Wiley and Sons, Inc., F. Ausubel et al., eds., 1994). DNA samples were then subjected to electrophoresis on 1.0 NuSeive (FMC BioProducts, Rockland, ME USA) agarose gels. DNA was visualized by exposure to ethidium bromide and long wave uv irradiation. DNA contained in slices isolated from the agarose gel was purified using the Bio 101 GeneClean Kit protocol (Bio 101 Vista, CA, USA).

Cloning ofH. pylori DNA sequences into the pET-28b prokaryotic expression vector.

The pET-28b vector was prepared for cloning by digestion with Ncol and EcoRI, or in the case of H. pylori protein 4821082 with NdeI and EcoRI (Current Protocols in Molecular Biology, John Wiley and Sons, Inc., F. Ausubel et al., eds., 1994). In the case of cloning ppiB, the pET-28a vector, which encodes a His-Tag that can be fused to the end of an inserted gene, was used and the cloning site prepared for cloning with the ppiB gene by digestion with BaHI and Xhol restriction endonucleases.

Following digestion, DNA inserts were cloned (Current Protocols in Molecular Biology, John Wiley and Sons, Inc., F. Ausubel et al., eds., 1994) into the previously digested pET-28b expression vector, except for the amplified insert for ppiB, which was cloned into the pET-28a expression vector. Products of the ligation reaction were then used to transform the BL21 strain of E. coli (Current Protocols in Molecular Biology, John Wiley and Sons, Inc., F. Ausubel et el., 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 with recombinant pET expression plasmids carrying the cloned H. pylori sequences according to standard methods (Current Protocols in Molecular, John Wiley and Sons, Inc., F. Ausubel et al., eds., 1994). Briefly, 1 microliter ofligation reaction WO 98/24475 PCT/US97/22104 was mixed with 50 microliters of electrocompetent cells and subjected to a high voltage pulse, after which, samples were incubated in 0.45 milliliters SOC medium yeast extract, 2.0 tryptone, 10 mM NaC1, 2.5 mM KC1, 10 mM MgC12, 10 mM MgSO4 and mM glucose) at 37 0 C with shaking for 1 hour. Samples were then spread on LB agar plates containing 25 microgram/ml kanamycin sulfate for growth overnight.

Transformed colonies of BL21 were then picked and analyzed to evaluate cloned inserts as described below.

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

Isolation and Preparation ofplasmid DNA from BL21 transformants Individual clones of recombinant pET-28b vectors carrying properly cloned H.

pylori ORFs were picked and incubated in 5 mis of LB broth plus 25 microgram/ml kanamycin sulfate overnight. The following day plasmid DNA was isolated and purified using the Qiagen plasmid purification protocol (Qiagen Inc., Chatsworth, CA,

USA).

Expression of recombinant H. pylori sequences in E. coli The pET vector can be propagated in any E. coli K-12 strain e.g. HMS1 74, HB101, JM109, DH5, etc. for the purpose of cloning or plasmid preparation. Hosts for expression include E. coli strains containing a chromosomal copy of the gene for T7 RNA polymerase. These hosts are lysogens of bacteriophage DE3, a lambda derivative that carries the lacI gene, the lacUV5 promoter and the gene for T7 RNA polymerase.

T7 RNA polymerase is induced by addition of isopropyl-B-D-thiogalactoside (IPTG), and the T7 RN A polymerase transcribes any target plasmid, such as pET-28b, carrying a T7 promoter and a gene of interest. Strains used include: BL21(DE3) (Studier, F.W., Rosenberg, Dunn, and Dubendorff, J.W. (1990) Meth. Enzymol. 185, 60-89).

To express recombinant H. pylori sequences, 50 nanograms of plasmid DNA isolated as described above was used to transform competent BL21(DE3) bacteria as described above (provided by Novagen as part of the pET expression system kit). The lacZ gene (beta-galactosidase) was expressed in the pET-System as described for the H.

WO 98/24475 PCT/US97/22104 -76pylori recombinant constructions. Transformed cells were cultured in SOC medium for 1 hour, and the culture was then plated on LB plates containing 25 micrograms/ml kanamycin sulfate. The following day, bacterial colonies were pooled and grown in LB medium containing kanamycin sulfate (25 micrograms/ml) to an optical density at 600 nM of 0.5 to 1.0 O.D. units, at which point, 1 millimolar IPTG was added to the culture for 3 hours to induce gene expression of the H. pylori recombinant DNA constructions.

After induction of gene expression with IPTG, bacteria were pelleted by centrifugation in a Sorvall RC-3B centrifuge at 3500 x g for 15 minutes at 4 0 C. Pellets were resuspended in 50 milliliters of cold 10 mM Tris-HC1, pH 8.0, 0.1 M NaCI and 0.1 mM EDTA (STE buffer). Cells were then centrifuged at 2000 x g for 20 min at 4 0

C.

Wet pellets were weighed and frozen at -80 0 C until ready for protein purification.

III. Purification of recombinant proteins from E. coli Analytical Methods The concentrations of purified protein preparations were quantified spectrophotometrically using absorbance coefficients calculated from amino acid content (Perkins, S.J. 1986 Eur. J. Biochem. 157, 169-180). Protein concentrations were also measured by the method of Bradford, M.M. (1976) Anal. Biochem. 72, 248-254, and Lowry, Rosebrough, Farr, A.L. Randall, R.J. (1951) J. Biol. Chem. 193, pages 265-275, using bovine serum albumin as a standard.

SDS-polyacrylamide gels (12% or 4.0 to 25 acrylamide gradient gels) were purchased from BioRad (Hercules, CA, USA), and stained with Coomassie blue.

Molecular weight markers included rabbit skeletal muscle myosin (200 kDa), E. coli galactosidase (116 kDa), rabbit muscle phosphorylase B (97.4 kDa), bovine serum albumin (66.2 kDa), ovaibumin (45 kDa), bovine carbonic anhydrase (31 kDa), soybean trypsin inhibitor (21.5 kDa), egg white lysozyme (14.4 kDa) and bovine aprotinin kDa).

1. Purification of soluble proteins All steps were carried out at 4 0 C. Frozen cells were thawed, resuspended in volumes of lysis buffer (20 mM Tris, pH 7.9, 0.5 M NaCI, 5 mM imidazole with glycerol, 0.1 2-mercaptoethanol, 200 ltg/ ml lysozyme, 1 mM phenylmethylsulfonyl fluoride (PMSF), and 10 ug/ml each ofleupeptin, aprotinin, pepstatin, L-l-chloro-3-[4tosylamido]-7-amino-2-heptanone (TLCK), L-l-chloro-3-[4-tosylamido]-4-phenyl-2butanone (TPCK), and soybean trypsin inhibitor, and ruptured by several passages through a small volume microfluidizer (Model M-110S, Microfluidics International WO 98/24475 PCTllS97/22104 -77- Corporation, Newton, MA). The resultant homogenate was made 0.1 Brij 35, and centrifuged at 100,000 x g for 1 hour to yield a clear supernatant (crude extract).

Following filtration through a 0.8 pm Supor filter (Gelman Sciences, FRG) the crude extract was loaded directly onto a Ni 2 nitrilotriacetate-agarose (NTA) with a milliliter bed volume (Hochuli, Dbeli, and Schacheer, A. (1987) J.

Chromatography 411, 177-184) pre-equilibrated in lysis buffer containing 10 glycerol, 0.1 Brij 35 and 1 mM PMSF. The column was washed with 250 ml (50 bed volumes) of lysis buffer containing 10 glycerol, 0.1 Brij 35, and was eluted with sequential steps of lysis buffer containing 10 glycerol, 0.05 Brij 35, 1 mM PMSF, and 20, 100, 200, and 500 mM imidazole in succession. Fractions were monitored by absorbance at OD 2 8 0 nm, and peak fractions were analyzed by SDS-PAGE. Fractions containing the recombinant protein eluted at 100 mM imidazole.

Recombinant protein 14640637 andproteins, beta-galactosidase (lacZ) andpeptidylprolyl cis-trans isomerase (ppiB) Fractions containing the recombinant proteins from the Ni2+-NTA-agarose columns were pooled and then concentrated to approximately 5 ml by centrifugal filtration (Centriprep-10, Amicon, MA), and loaded directly onto a 180-ml column (1.6 X 91 cm) of Sephacryl S-100 HR gel filtration medium equilibrated in Buffer A (10 mM Hepes, pH 7.5, 150 mM NaCI, 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 by SDS-PAGE. Fractions were pooled and concentrated by centrifugal filtration.

Recombinnt protein 7116626 Fractions containing the recombinant protein from the Ni 2 -NTA-agarose column were pooled and dialyzed overnight against 1 liter of dialysis buffer (10 mM MOPS, pH 6.5, 50 mM NaCI, 0.1 mM EGTA, 0.02% Brij 35 and 1 mM PMSF). In the morning, a fine white precipitate was removed by centrifugation and the resulting supernatant was loaded onto an 8 ml (8 x 75 mm) MonoS high performance liquid chromatography column (Pharmacia Biotechnology, Inc., Piscataway, NJ, USA) equilibrated in buffer B (10 mM MOPS, pH 6.5, 0.1 mM EGTA) containing 50 mM NaCI. The column was washed with 10 bed volumes of buffer B containing 50 mM NaCI, and developed with a 50-ml linear gradient of increasing NaCI (50 to 500 mM).

Recombinant protein 7116626 eluted as a sharp peak at 300 mM NaC1.

WO 98/24475 PCT/US97/22104 -78- 2. Purification of insoluble proteins from inclusion bodies The following steps were carried out at 4 0 C. Cell pellets were resuspended in lysis buffer with 10% glycerol 200 pg/ ml lysozyme, 5 mM EDTA, 1mM PMSF and 0.1 -mercaptoethanol. After passage through the cell disrupter, the resulting homogenate was made 0.2 deoxycholate, stirred 10 minutes, then centrifuged at 20,000 x g, for min. 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 2mercaptoethanol. The resulting white pellet was composed primarily of inclusion bodies, free of unbroken cells and membranous materials.

Recombinant proteins 26054702, 16225006, 30100332, 4721061 The following steps were carried out at room temperature. Purified inclusion bodies were dissolved in 20 ml 8.0 M urea in lysis buffer with 1 mM PMSF and 0.1 2-mercaptoethanol, and incubated at room temperature for 1 hour. Materials that did not dissolve were removed by centrifugation. The clear supematant was filtered, then loaded onto a Ni 2 -NTA agarose column pre-equilibrated in 8.0 M urea in Lysis Buffer. The column was washed with 250 ml (50 bed volumes) of lysis buffer containing 8 M urea, 1.0 mM PMSF and 0.1 2-mercaptoethanol, and developed with sequential steps of lysis buffer containing 8M urea, 1 mM PMSF, 0.1 2mercaptoethanol and 20, 100, 200, and 500 mM imidazole in succession. Fractions were monitored by absorbance at OD 2 80 nm, and peak fractions were analyzed by SDS- PAGE. Fractions containing the recombinant protein eluted at 100 mM imidazole.

Recombinani proteins 29479681, 26380318 The pellet containing the inclusion bodies was solubilized 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 x g for min, and the cleared 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 the column with 10 b.d volumes, the column was developed with a linear gradient from 0 to 500 mM NaCl.

Dialysis and concentration ofprotein samples Urea was removed slowly from the protein samples by dialysis against Trisbuffered saline (TBS; 10 mM Tris pH 8.0, 150 mM NaCI) containing 0.5 deoxycholate (DOC) with sequential reduction in urea concentration as follows; 6M, WO 98/24475 PTU9/20 PCTIUS97/22104 79 4M, 3M, 2M, I M, 0.5 M and finally TBS without any urea. Each dialysis step was conducted for a minimum of 4 hours at room temperature.

After dialysis, samples were concentrated by pressure filtration using Amicon stirred-cells. Protein concentrations were measured using the methods of Perkins (1986 Eur. J. Biochem. 157, 169-180), Bradford ((1976) Anal. Biochem. 72, 248-254) and Lowry ((195 1) J1. Biol.- Chem. 193, pages 265 -275).

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

TABLE 4 J99 Homolog Gene Bacterial cell Method of Relative Final Composit Sequence identified symbol fraction used to purification MW on concentratio ionof Identifier by Blast of purify SDS- n of purified buffer Homolog recombinant PAGE gel protein proteins Outer Membrane Proteins 16225006 P28635 YEAC Inclusion bodies His-Tag 18 kDa 5 mg/mI B 26054702 P15929 fIgH Inclusion bodies His-Tag 37 kDa 1. 18 mg/mI B as dry 7116626 P26093 e(P4) Soluble fraction His-Tag 29 kDa 0.8 mg/mI A mg/mI C 29479681 P13036 fecA Inclusions SP- 23 kDa 2.36 mg/mI B bodies Sephaos

B

as dry pellet 14640637 P16665 TPF1 Soluble fraction His-Tag 17 kDa 2.4 mg/mI A filtration SIOO HR I Periplasmic/SecretedProtein 31)032 P23 847 dppA Inclusion bodies His-Tag I11 kDa 2.88 mg/mI B 4721061 P36175 GCP Inclusion bodies His-Tag 38 kDa 2.8 mg/mI B WO 98/24475 PCTIUS9722104 Other Surface Proteins 4821082 P08089 M Inclusion bodies His-Tag 20 kDa 1.16 mg/ml B protein 978477 L28919 FBP54 Inclusion bodies SP- 44 kDa 2.56 mg/ml B Sepharose 0.3 mg/ml B Inner Membrane Proteins 26380318 P15933 fliG Inclusion bodies SP- 11 kDa 22 mg/ml B Sepharose Control Proteins with His-Tag P00722 lacZ Soluble fraction His-Tag 116 kDa 10 mg/ml A gel filtration S200 HR ppiB Soluble fraction His-Tag 21 kDa 4.4 mg/ml A gel filtration S100 HR Buffer composition s: mM Hepes pH 7.5, 150 mM NaCI, 0.1 mM EGTA B= 10 mM Tris pH 8.0, 150 mM NaCI, 0.5 DOC C= 10 mM MOPS pH 6.5, 300 mM NaCI, 0.1 EGTA IV. Analysis of H. pylori proteins as Vaccine candidates To analyze H. pylori proteins for use in the vaccine formulations of the invention, several H. pylori proteins were expressed, characterized immunologically and tested in animal efficacy studies as outlined below. Specifically, the immunomodulatory effects of H. pylori proteins were investigated in a mouse/H pylori model which mimics the human H. pylori infection in humans. In these studies, the effect of oral immunization of selected H. pylori polypeptides in H. pylori infected mice was determined.

Identification, cloning and expression ofrecombinant Helicobacter pylori sequences.

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

WO 98/24475 PCT/US97/22104 -81 PCR amplification and cloning ofDNA sequences containing ORFsfor membrane and secreted proteins from the J99 strain ofHelicobacter pylori.

The sequences selected (from the list of the DNA sequences of the invention) for cloning from H. pylori strain J99 were prepared for amplification cloning by the polymerase chain reaction (PCR). All of the selected sequences encode for outer membrane H. pylori proteins, with vac9 (SEQ ID NO:125), vacl0 (SEQ ID NO:147), vac22 (SEQ ID NO:121) and vac41 (SEQ ID NO:176) sequences all sharing a terminal phenylalanine residue. Likewise, the vac32 (SEQ ID NO:108), vac36 (SEQ ID NO:149) and vac37 (SEQ ID NO: 139) sequences all share a terminal phenylalanine residue and a tyrosine cluster at the C-terminus. Synthetic oligonucleotide primers for each ORF of interest (Table 5) specific for the predicted mature 5' end of the ORF and downstream of the predicted translational termination codon were designed and purchased (GibcoBRL Life Technologies, Gaithersburg, MD, USA). All forward primers (specific for the 5' terminus of the region of ORF of interest) were designed to include a BamIII restriction site followed by a NdeI restriction site. These primers were designed to permit the initiation of protein translation at a methionine residue encoding within the NdeI restriction site sequence (in the case of producing a non His-tagged recombinant protein) or to fuse in frame with the DNA sequence encoding the His-tag (for producing His-tagged recombinant protein), followed by the coding sequence for the remainder of the native H. pylori DNA. All reverse oligonucleotide primers (specific for downstream of the predicted translational termination codon of the ORF) were designed to include an EcoRI restriction site at the 5' terminus. This combination of primers would enable each ORF of interest to be cloned into pET28b (to produce a His-tagged recombinant protein) or pET30a k(t produce a non His-taggUed or ative recombinant protein). The pET28b vector provides sequence encoding an additional 20 aminoterminal amino acids (plus the methionine in the NdeI restriction site) including a stretch of six histidine residues which makes up the His-tag.

Genomic DNA prepared from H. pylori strain J99 (ATCC 55679) was used as the source of template DNA for the PCR amplification reactions (Current Protocols in Molecular Biology, John Wiley and Sons, Inc., F. Ausube, et al., eds., 1994). To amplify a DNA sequence containing a specific H. pylori ORF, genomic DNA nanograms) was introduced into a reaction tube containing 200 nanograms of both the forward and reverse synthetic oligonucleotide primer specific for the ORF of interest, and 45 microliters of PCR SuperMix purchased (GibcoBRL Life Technologies, Gaithersburg, MD, USA) in a total of 50 microliters. The PCR SuperMix is supplied in 1.1X concentrations and contains 22mM Tris-HCI (pH 55mM KC1, 1.65 mM WO 98/24475 WO 9824475PCT/US97/22104 82 MgCl 2 220 micromolar of each dATP, dCTP, dGTP and dTTP, 22 units recombinant Taq polymerase/mi and stabilizers. The following thermal cycling conditions were used to obtain amplified DNA products for each ORF using a Perkin Elmer Cetus/Gene Amp PCR System thermal cycler.

Table 5: Oligonucleotide primers Gene Forward primer Reverse primer vac9 CGCGGATCCATATGGCTGAAA CCGGAATTCATCAGTATTCAA (nt SEQ ID AAACGCCTTTTTTTAAAACTAA TGGGAATAAAGCC (SEQ ID NO:28) AAACCAC (SEQ ID NO: 257) NO: 258) (aa SEQ ID NO:_125) vacl 0 CGCGGATCCATATGAAAGAAG CCGGAATTCGCTTAAAAGAAA (nt SEQ ID AAGAAAAAGAAGAAAAAAAG ATAGTCCCCCAAACGC (SEQ ACAGAAAGG (SEQ ID NO: 259) ID NO: 260) (aa SEQ ID NO: 147) vac22 CGCCGGATCCATATGAAAGAG CCGGAATTCATATAAATATCA (nt SEQ ID GTCATTCCACCCCTTCAACCCC TATAGGCAGAAAAAC (SEQ ID NO:24) (SEQ ID NO: 261) NO: 262) (aa SEQ ID NO: 121) vac32 CGCGGATCCATATGGAGGCAG CCGGAATTCGATTGATTTTGTC (nt SEQ ID AGCTTGATGAAAAATC (SEQ I1) AAATCIAAAATCCC (SEQ I NO: 11) NO: 263) NO: 264) (aa SEQ ID NO: 108) vac3 6 (hop TATTATACATATGGAAGAAGA TAATCTCGAGTTTAGAAGGCG B) TGGG (SEQ ID NO: 265) TA (SEQ ID NO: 266) (nt SEQ ID NO:52) (aa SEQ ID NO:149) WO 98/24475 PCTIUS97/22104 -83 vac37 TTATATTCATATGGAAGACGAT AATTCTCGAGCCTCTTTATAA (i-hop) GGC (SEQ ID NO: 267) GCC (SEQ ID NO: 268) (nt SEQ ID NO:42) (aa SEQ ID NO: 139) vac41 CGCGGATCCATATGGTAGAAG CCGGAATTCGGAGCCAATAGG (nt SEQ ID CCTTTCAAAAACACCAAAAAG GAGCTAAAGCC (SEQ ID NO: NO:79) ACGG (SEQ ID NO: 269) 270) (aa SEQ ID NO: 176) Sequences for Vac32, Vac9 and Vac22 Denaturation at 94 0 C for 30 sec cycles at 94 0 C for 15 sec, 55°C for 15 sec, and 72 0 C for 1.5 min Reactions were concluded at 72 0 C for 8 minutes Sequences for Vacl0 and Vac41 Denaturation at 94°C for 30 sec cycles at 94 0 C for 15 sec, 55°C for 15 sec, and 72 0 C for 2.5 min Reactions were concluded at 72 0 C for 8 minutes Sequences for Vac36 and Vac37 Denaturation at 2 cycles at 94°C for 15 sec, 30°C for 15 sec, and 72 0 C for 1.5 min 23 cycles at 94C for 15 sec, 55°C for 15 see, and 72 0 C for 1.5 min Reactions were concluded at 72 0 C for 6 minutes Upon completion of the thermal cycling reactions, each sample of amplified DNA was subjected to electrophoresis on 1.0% agarose gels. The DNA was visualized '0 by exposure to ethidium bromide and long wave UV irradiation, and cut out in gel slices. DNA was purified using the Wizard PCR Preps Kit (Promega Corp., Madison, WI, USA), and then subjected to digestion with BamHI and EcoRI (Current Protocols in Molecular Biology, John Wiley and Sons, Inc., F. Ausubel et al., eds., 1994). The digested PCR amplicon was then re-electrophoresed and purified as before.

WO 98/24475 PCT/US97/22104 84- Ligation of H. pylori DNA sequences into cloning vectors The pOK12 vector Vieira and J. Messing, Gene 100:189-194, 1991) was prepared for cloning for digestion with BamHI and EcoRI in the case of Vac9, 10, 22, 31 and 32, whereas the pSU21 vector Bartolome et al., Gene 102:75-78, 1991) was prepared for cloning by digestion with BamHI and EcoRI in the case of Vac 41 (Current Protocols in Molecular Biology, John Wiley and Sons, Inc., F. Ausubel et al., eds., 1994). The vectors were subjected to electrophoresis on 1.0% agarose gels and purified using the Wizard PCR Preps kit (Promega Corp., Madison, WI, USA). Following ligation of the purified, digested vector and the purified, digested amplified H. pylori ORF, the products of the ligation reaction were transformed into E. coli JM 109 competent cells according to standard methods (Current Protocols in Molecular Biology, John Wiley and Sons, Inc., F. Ausubel et al., eds., 1994). Individual bacterial colonies were screened for those containing the correct recombinant plasmids by incubating in LB broth overnight (plus 25ug/ml kanamycin sulfate for the pOK12 based plasmids or 25ug/ml chloramphenicol for the pSU21 based plasmids) followed by plasmid DNA preparation using the Magic Minipreps system (Promega Corp., Madison, WI, USA), and then analyzed by restriction digestion (Current Protocols in Molecular Biology, John Wiley and Sons, Inc., F. Ausubel et al., eds., 1994).

Cloning ofH. pylori DNA sequences into the pET28b and pET30a prokaryotic expression vectors Both the pET28b and pET30a expression vectors were prepared for cloning by digestion with NdeI and EcoRI (Current Protocols in Molecular Biology, John Wiley and Sons, Inc., F. Ausubel et al., eds., 1994). The H. pylori DNA sequences were .J removeu Hu pl .Jr 1 .i.L k v ac, 1n I tiu J) or acV t ppa U2IkvaI u removed from pOK12 (Vac9,1023,31 and 32) or pSU21 (Vac41) plasmid backbones by digestion with NdeI and EcoRI (Current Protocols in Molecular Biology, John Wiley and Sons, Inc., F. Ausubel et al., eds., 1994). The pET28b, pET30a and H. pylori DNA sequences were all electrophoresed on a 1% agarose gel and purified using the Wizard PCR Preps kit (Promega Corp., Madison WI, USA). Following ligation of the purified, digested expression vector and the purified, digest H. pylori DNA sequences, the products of the ligation reaction were transformed into E. coli JM 109 competen. cells (Current Protocols in Molecular Biology, John Wiley and Sons, Inc., F. Ausubel et al., eds., 1994). Individual bacterial colonies were screened for those containing the correct recombinant plasmids by preparing plasmid DNA as described above followed by analysis by restriction digestion profiles and DNA sequencing (Current Protocols in Molecular Biology, John Wiley and Sons, Inc., F. Ausubel et al., eds., 1994). These recombinant plasmids were then used to transform specific E. coli expression strains.

WO 98/24475 PCTIUS97/22104 Transformation of competent bacteria with recombinant expression plasmids Competent bacterial strains (BL21 (DE3), BL21 (DE3)pLyS, HMS 174(DE3) and HMS 174(DE3)pLysS were prepared and transformed with the recombinant pET28b expression plasmids carrying the cloned H. pylori sequences according to standard methods (Current Protocols in Molecular Biology, John Wiley and Sons, Inc., F.

Ausubel et al., eds., 1994). These expression host strains contain a chromosomal copy of the gene for T7 RNA polymerase. These hosts are lysogens of bacteriophage DE3, a lambda derivate that carries the lad gene, the lacUV5 promoter and the gene for T7 RNA polymerase. T7 RNA polymerase expression is induced by the addition of isopropyl-p-D thiogalactoside (1PTG), and the T7 RNA polymerase then transcribes any target plasmid, such as pET28b, that carries a T7 promoter sequence and a gene of interest.

Expression of recombinant H. pylori sequences in E. coli Transformants were collected from LB agar plates containing kanamycin sulfate (ensures maintenance of the pET28b-based recombinant plasmids) and used to inoculate LB broth containing 25ug/ml kanamycin sulfate and grown to an optical density at 600nm of 0.5 to 1.0 OD units, at which point ImM 1PTG was added to the culture for one to three hours to induce gene expression of the H. pylori recombinant DNA constructions. After induction of gene expression with 1PTG, bacteria were pelleted by centrifugation and resuspended in SDS-PAGE solubilization buffer and subjected to SDS-PAGE (Current Protocols in Molecular Biology, John Wiley and Sons, Inc., F. Ausubel et al., eds., 1994). Proteins were visualized by staining WILI Cooma1ssie Brilliant Blue or Ldetected by western immunoblotting using the specific anti-His tag monoclonal antibody (Clontech, Palo Alto, CA, USA) using standard methods (Current Protocols in Molecular Biology, John Wiley and Sons, Inc., F.

Ausubel et al., eds., 1994). The host strain that provided the highest level of recombinant protein production was then chosen for use in a large-scale induction in order to purify the recombinant protein. All of the following proteins listed were expressed recombinantly and the strain giving the highest level of expression listed: BL21(DE3) (vac31, vac26, vac37); BL21(DE3) pLysS (vac 9, 32); HMS174(DE3) (vacl0,11).

WO 98/24475 PCT/US97/22104 86 Purification of recombinant proteins and generation ofspecific antiserum Large scale cultures were inoculated and grown as above, and induced with ImM 1PTG for 3 hours. After induction, bacteria were pelleted by centrifugation in a Sorvall centrifuge at 3500 x g for 15 min at 4°C. All of the expressed recombinant proteins were present in the insoluble inclusion body fraction. Inclusion bodies were purified according to standard protocols (Antibodies, Cold Spring Harbor Laboratory Press, E.

Harlow and D. Lane, eds., 1988). The recombinant protein produced by vac32 was solubilized in 8M urea and partially purified by nickel chromatography (REF here).

Denatured recombinant proteins were purified by electrophoresis on SDS-PAGE gels, and after visualization with Coomassie Brilliant Blue, the protein was excised from the gel and the gel slices homogenized. This material was used to raise specific polyclonal antibodies in mice or rabbits according to standard protocols (Antibodies, Cold Spring Harbor Laboratory Press, E. Harlow and D. Lane, eds., 1988).

Immunological characterization ofrecombinant proteins In all cases where antibody was attempted to be raised, high titre antisera was generated, confirming the immunogenicity of the recombinant proteins. Further, these specific antisera were used to analyze whether the protein encoded by the cloned gene was expressed in H. pylori. Western immunoblot analysis using standard protocols (Current Protocols in Molecular Biology, John Wiley and Sons, Inc., F. Ausubel et al., eds., 1994) confirmed that the H. pylori strain J99 did express proteins of the expected molecular weight that reacted with the vacl0, vac32, vac31, vac36 antiserum. The specific antiserum was also used to determine the level of antigenic conservation between a large number of H. pylori isolates that had been obtained from distinct geographical sites around the world, and from all types of clinical manifestations, including gastritis, duodenal ulcer, gastric ulcer and gastric cancer. It was found that every strain produced a protein that reacted specifically with each antiserum.

Further, H. pylori cells from strains J99, 17874, AH244 and SSI were fractionated into different cellular compartments (Doig and Trust 1994 Infect. Immun.

62:4526-4533: O'Toole et al. 1995 J. Bacteriol. 177:6049-6057). The specific antiserum was used to probe .hese fractions by western immunoblot to identify in which fraction the protein was localized. In all cases, the immunoreactive protein was present in the outer membrane as had been predicted by the sequence features and motif searches described herein.

WO 98/24475 PCT/US97/22104 -87- Demonstration ofprotein efficacy as a vaccine Purification of vac36 for efficacy studies All the following steps were carried out at 4 0 C. Cell pellets were resuspended in volumes per gram of cell of lysis buffer (50mM Sodium Phosphate pH 8.0, 0.5 M NaC 1, 5mM Imidazole) with 10mM EDTA, 1 mM phenylmethylsulfonyl fluoride (PMSF) and 0.1 p-mercaptoethanol, and ruptured by several passages through a small volume microfluidizer (Model M- 10S, Microfluidics International Corporation, Newton, MA). The resulting homogenate was made 0.2% sodium deoxycholate (DOC), stirred 20 minutes, then centrifuged (10,000 g x 30 min). The pellets were washed twice with Lysis Buffer containing 10mM EDTA, 1% Triton X-100, 1 mM PMSF and 0.1% P -mercaptoethanol, then with lysis buffer containing 1M urea, ImM PMSF and 0.1 pmercaptoethanol. The resulting white pellet is composed primarily of inclusion bodies, free of unbroken cells and membranous materials.

The inclusion bodies were dissolved in 20 ml 6M guanidine-HC1 in lysis buffer with 1 mM PMSF and 0.1% P-mercaptoethanol, and incubated on ice for 1 hour.

Materials that did not dissolve were removed by centrifugation (100,000 g x 30 min.) The clear supernatant was filtered through a 0.8 pm Supor filter (Gelman Sciences, FRG) and then load directly onto a 10 ml Ni 2 NTA agarose column (Hochuli et al.

1987) pre-equilibrated in 6M guanidine-HCl in Lysis Buffer containing 1 mM PMSF and 0.1% p-Mercaptoethanol. The column was washed with 20ml (2 bed volumes) of Lysis Buffer containing 6M guanidine-HCl, ImM PMSF and 0.1 %p-mercaptoethanol, then guanidine-HCl was removed slowly with a 100 ml linear gradient (from 6M to 0 M Guanidine-HCl) of lysis buffer containing 0.5% Brij 35, 1 mM PMSF, 0.1% Pmercaptochanol. Next, the column was developed with a 25 ml linear gradient of increasing imidazole (5 to 500 mM) in Lysis buffer containing rij 35, 1 mM PMSF and 0.1% p-mercaptoethanol. The recombinant proteins elute as a peak centered at 100mM imidazole.

Fractions containing the recombinant proteins were pooled and then concentrated to approximately 8 ml by centrifugal filtration (Centriprep-10, Amicon, MA), and loaded directly onto a 350-ml column (2.2 X 91 cm) of Sephacyl S-100 HR gel filtration medium equilibrated in Buffer A (50mM Sodium Phosphate, pH 8.0, 500 mM NaC 1, 0.1 mM EGTA, 1 mM PMSF, 0.1%p-mercaptoethanol, 0.5% Brij 35) and ran in Buffer A at 30 ml/h. Fractions containing the recombinant protein were identified by absorbance at 280 nm and analyzed by SDS-PAGE. Fractions were pooled, concentrated to 1.5 to 2 mg/ml and dialysed overnight against 10 mM Potassium Phosphate pH 7.5, 150 mM NaCI, 0.1 mM EGTA and 0.5% Brij 35. The concentration of protein in the dialysate was quantified, then aliquoted prior to freezing at 20 0

C.

WO 98/24475 PCTIUS97/22104 -88- Mouse model of Heliocobacter pylori infection A murine model ofH. pylori infection was produced by infection of C57BL/6 mice with with H. pylori Sydney strain SS1 and was used to assess the efficacy of recombinant H. pylori vac36. This mouse-adapted H. pylori strain is cagA+ vacA+, shows colonization levels in C57BL/6 mice equivalent to those observed in humans, forms adhesion pedestals, colonizes for at least 8 months, and elicits a chronic-active gastritis and mucosal atrophy (Lee et al., Gastroenterology, 112:1386-1397, 1997).

Dose-response studies have shown 100% infection rates of inbred C57BL/6 and Balb/C mice at 8 weeks post-challenge with a single inoculation of 106 organisms.

Assessment of gastric H. pylori infection The presence of H. pylori organisms in gastric tissue was determined by culture of gastric tissue and by a quantitative urease assay. In the latter method, a longitudinal segment of antrum, representing approximately /4 of the total antral region was placed in 1 ml of urea broth. After 4 hr, the extent of color change resulting from urea hydrolysis and increased pH was quantiated by spectrophotometric measurement of A 5 5 0 (Fox et al., Immunol. 88:400-406, 1996). The assay sensitivity is 103 H pylori organisms. A positive pylori-infected) gastric tissue was defined as that sample showing 2 standard deviations above the mean A 5 5 0 value derived from a group of unchallenged uninfected age-matched control mice.

Assessment of local immune response to immunization in gastric tissue Longitudinal sections of gastric tissues from the esophageal to the duodenal junction were emIbeddeUUd iln OC embeddIU g UUill II.compound, IfronLI Illliquid nitrogenLJll, Iand cryosections immunostained with monoclonal antibodies recognizing CD4+ or CD8+T cells or with antisera against mouse IgA for identification of IgA containing (IgACC) plasma cells (Pappo et al., Infect. Immun. 63:1246-1252, 1995). The degree of local gastric immune response was expressed quantitatively as the number of CD4+, CD8+ or.

IgACC cells per mm 2 of gastric region examined.

Protective activity of purified recombinant H. pylori vac36 antigen The ability of purified recombinant vac36 antigen derived from H. pylori to interfere with the establishment of an H. pylori infection was examined in mice. Groups (n=10) of 6-8 week-old female C57BL/6 mice were immunized orally 4 times at weekly intervals as follows: 1) 100 p.g of recombinant vac36 antigen and 10 .ig cholera toxin (CT) adjuvant, 2) 1 mg H pylori lysate antigens and 10 jig CT, and 3) 0.2 M WO 98/24475 PCT[US97/22104 -89bicarbonate buffer and 10 ug CT adjuvant. The mice were challenged 2 weeks later on 3 consecutive days by oral administration of 108 H. pylori organisms. The experiment was terminated 2 weeks post-challenge, and the H. pylori infection level assessed by bacterial colony counts and by quantitative urease assays.

Oral immunization with vac36 antigen interfered with the establishment of H.

pylori infection upon challenge with live H. pylori organisms. Mice immunized with purified recombinant vac36 antigen exhibited a significantly lower level of colonization by H. pylori, as assessed by gastric urease activity and bacterial count assays (Table 6).

Oral immunization with vac36 antigen also resulted in the generation of a local protective gastric immune response. Greater numbers of CD4+T cells and of IgACC were recruited in the gastric tissues of vac36-immunized mice when compared with unimmunized H. pylori-infected mice (Table 7).

Table 6 Recombinant vac36 antigen protects mice from challenge with H. pylori Vaccine Urease pb H pylori pb Treatment Activity a burdenc Group vac36 0.199±0.080 0.0022 55,800±12,599 0.0125 H. pylori lysate 0.057±0.007 0.0002 2,360±955 0.0002 buffer 1.655±0.420 131,000±18,39 1 a Urease activity is expressed as mean A 5 5 0± SEM of duplicate antral samples from n=10 mice/group.

b by Wilcoxon Rank Sum Test compared with mice immunized with CT adjuvant alone c The level ofH. pylori in gastric tissue was assessed by bacterial counts, and shown as mean colony forming units±SEM WO 98/24475 PCTIUS9722104 Table 7 vac36-immunized mice generate a local gastric immune response upon challenge with H. pylori Vaccine Treatme CD4+ CD8+ IgACC nt Group cardi corpu antru cardi corpu antru cardi corpu antru aa s m a s m a s m vac36 33+ 54+ 31±8 3±2 0 1±1 24 79 67 9 a 8* 12 16 13

H.

pylori 31 36 24 8 4±2 2±1 2+1 31 9 73 79 lysate 13 19 13* buffer 12 2 27 8 18 4 1±1 0 0 4±2 30 46 13 14 a Mean number of cells/mm 2 of gastric region SEM p<0.05 by Wilcoxon Rank Sum Test when compared with unimmunized H.

pylori infected mice V. Sequence Variance Analysis of genes in Helicobacter pylori strains Four genes were cloned and sequenced from several strains of H pylori to compare the DNA and deduced amino acid sequences. This information was used to determine the sequence variation between the H. pylori strain, J99, and other H. pylori strains isolated from human patients.

Preparation of Chromosomal DNA.

Cultures of H. pylori strains (as listed in Table 10) were grown in BLBB (1% Tryptone, 1% Peptamin 0.1% Glucose, 0.2% Yeast Extract 0.5% Sodium Chloride, Fetal Bovine Serum) to an OD600 of 0.2. Cells were centrifuged in a Sorvall RC-3B at 3500 x g at 4 0 C for 15 minutes and the pellet resuspended in 0.95 mls of 10 mM Tris- HCI, 0.1 mM EDTA Lysozyme was added to a final concentration of Img/ml along with, SDS to 1% and RNAse A TI to 0.5mg/ml and 5 units/ml respectively, and incubated at 37 0 C for one hour. Proteinase K was then added to a final concentration of 0.4mg/ml and the sample was incubated at 55 C for more than one hour. NaCI was added to the sample to a concentration of 0.65 M, mixed carefully, and 0.15 ml of WO 98/24475 WO 9824475PCT/US97/22104 -91 CTAB in 037M NaCL (final is 1% CTAB/7OmM NaCL) was added followed by incubation at 65 0 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 volumes) or isopropanol (0.6 x volumes) at -70*C for IOmninutes, washed in 70% EtOH and resuspended in TB.

PCR Amplification and cloning.

Genomic DNA prepared from twelve strains of Helicobacter pyloni was used as the source of template DNA for PCR amplification reactions (Current Protocols in Molecular Biology, John Wiley and Sons, Inc., F. Ausubel et al., editors, 1994). To amplify a DNA sequence containing an H. pylori ORF, genomic DNA (10 nanograms) was introduced into a reaction vial containing 2 mM MgCl2, 1 micromolar synthetic oligonucleotide primers (forward and reverse primers, see Table 8) complementary to and flanking a defined H pylori ORF, 0.2 mnM of each deoxynucleotide triphosphate; dATP, dGTP, dCTP, dTTP and 0.5 units of heat stable DNA polymerase (Amplitaq, Roche Molecular Systems, Inc., Branchburg, NJ, USA) in a final volume of microliters in duplicate reactions.

Table 8 Oligonucleotide primers used for PCR amplification of H.

Dylori DNA sequences.

[Outer membrane Forward primer 5' to 3' Reverse Primer 5' to 3' Proteins Protein 26054702 5'-TFTAACCATGGTGAAAA (for strains AH4, AHI15, GCGATA-3' (SEQ ID AACTTTAG-3 (SEQ ID AH6I, 5294, 5640, AHI18, NO:2 17) NO:218) and Protein 26054702 5'-TTAACCATGGTGAAAA 5'-TAGAATI7CGCATAA (for strains AH5, 5155, G CGATA-3' (SEQ ID CGATCAATC-3' (SEQ I D 7958, AH24,and 199) NO:2 19) NO:220) Protein 7116626 5'-ATATCCATGGTGAGTT TGATGA-3' (SEQ ID TTATTTTGCCA-3' (SEQ ID NO:221) NO:222) Protein 29479681 5'-AATTCCATGGCTATC CAAATCCG-3' (SEQ ID TCGTAGTATT-3- (SEQ ID NO:223) NO:224) Protein 346 5'-GATACCATGGAATTT AT GAAAAA G -3 SELQ I D TAGTTATAC-3' (SEQ ID 0"22) 22 6) WO 98/24475 PCTIUS97/22104 -92- 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 94C for 2 min, 2 cycles at 94 0 C for 15 sec, 30 0 C for 15 sec and 72 0 C for 1.5 min 23 cycles at 94 0 C for 15 sec, 55°C for 15 sec and 72 0 C for 1.5 min Reactions were concluded at 72 0 C for 6 minutes.

Protein 26054702 for strains AH5, 5155, 7958, AH24,and J99; Denaturation at 94 0 C for 2 min, 2 cycles at 94C for 15 sec, 30 0 C for 15 sec and 72 0 C for 1.5 min cycles at 94C for 15 sec, 55 0 C for 15 sec and 72 0 C for 1.5 min Reaction was concluded at 72 0 C for 6 minutes.

Protein 26054702 and Protein 294796813 for strains AH4, AH15, AH61, 5294, 5640, AH18, and Hp244; Denaturation at 94 0 C for 2 min, 2 cycles at 94 0 C for 15 sec, 30 0 C for 20 sec and 72 0 C for 2 min cycles at 94C for 15 sec, 55 0 C for 20 sec and 72 0 C for 2 min Reactions were concluded at 72 0 C for 8 minutes.

Upon completion of thermal cycling reactions, each pair of samples were combined and used directly for cloning into the pCR cloning vector as described below.

Cloning ofH. pylori DNA sequences into the pCR TA cloning vector.

All amplified inserts were cloned into the pCR 2.1 vector by the method described in the Original TA cloning kit (Invitrogen, San Diego, CA). Products of the ligation reaction were then used to transform the TOP 1OF' (INVaF' in the case of H.

pylori sequence 350) strain of E. coli as described below.

Transformation of competent bacteria with recombinant plasmids Competent bacteria, E coli strain TOPI OF' or E. coli strain INVaF' were transformed with recombinant pCR expression plasmids carrying the cloned H. pylori sequences according to standard methods (Current Protocols in Molecular Biology, John Wiley and Sons, Inc., F. Ausubel et al., editors, 1994). Briefly, 2 microliters of WO 98/24475 PCTIUS97/22104 -93micromolar BME was added to each vial of 50 microliters of competent cells.

Subsequently, 2 microliters of ligation reaction was mixed with the competent cells and incubated on ice for 30 minutes. The cells and ligation mixture were then subjected to a "heat shock" at 42 0 C for 30 seconds, and were subsequently placed on ice for an additional 2 minutes, after which, samples were incubated in 0.45 milliliters SOC medium yeast extract, 2.0 tryptone, 10 mM NaCl, 2.5 mM KC1, 10 mM MgC12, 10 mM MgSO4 and 20, mM glucose) at 37 0 C with shaking for 1 hour. Samples were then spread on LB agar plates containing 25 microgram/ml kanamycin sulfate or 100 micrograms/ml ampicillan for growth overnight. Transformed colonies of TOP OF' or INVaF' were then picked and analyzed to evaluate cloned inserts as described below.

Identification ofrecombinant PCR plasmids carrying H. pylori sequences Individual TOP 1OF' or INVaF' clones transformed with recombinant pCR- H.pylori ORFs were analyzed by PCR amplification of the cloned inserts using the same forward and reverse primers, specific for each H. pylori sequence, that were used in the original PCR amplification cloning reactions. Successful amplification verified the integration of the H. pylori sequences in the cloning vector (Current Protocols in Molecular Biology, John Wiley and Sons, Inc., F. Ausubel et al., editors, 1994).

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

WO 98/24475 PTU9/20 PCTfIJS97/22104 -94- Table 9 Oligonuclegfide primers used for sequencing of H pylori DNA sequences.

Outer membrane Forward primers 5' to 3' Reverse Primers 5' to 3' Proteins Protein 26054702 5'CCCTTCATTTTAGAAATC G-3' (SEQ ID NO:227) (SEQ ID NO:234) GCG-3' (SEQ ID NO:228) A-3'(SEQ ID NO:235) GCT-3' (SEQ ID NO:229) (SEQ ID NO:236) GAAGT-3' (SEQ ID NO:230) GATCG-3' (SEQ ID NO:23 1) GAAGT-3' (SEQ ID NO:232) TTGGT-3' (SEQ ID NO:233). Protein 7116626 5'TTGAACACTTTTGATTAT GCGG-3' (SEQ ID NO:237) TC-3' (SEQ ID NO:239) (SEQ ID NO:238) (SEQ ID NO:240) Protein 5'CTTATGGGGGTATTGTC 29479681 A-3'(SEQ ID NO:241) (SEQ ID NO:243) ID NO:242). 3'(SEQ ID NO:244) Protein 346 5'ACCAATATCAATTGGCA CT-3' (SEQ ID NO:245) 3'(SEQ ID NO:247) ~A ATi/ A C VP~~ 1t- A A f T'f' flr ID NO:246) 3' (SEQ ID NO:248) TTTAG-3' (SEQ ID NO:249) CAT-3'(SEQ ID NO:25 1) TGAAG-3' (SEQ ID NO:250) TTGTC-3'(SEQ ID NO:252) Vector Primers 5'-GTAAAACGACGGCCAG- 3'(SEQ ID NO:253) 3'(SEQ ID NO:254) WO 98/24475 PCT/US97/22104 Results To establish the PCR error rate in these experiments, five individual clones of Protein 26054702, prepared from five separate PCR reaction mixtures from H. pylori strain J99, were sequenced over a total length of 897 nucleotides for a cumulative total of 4485 bases of DNA sequence. DNA sequence for the five clones was compared to a DNA sequence obtained previously by a different method, random shotgun cloning and sequencing. The PCR error rate for the experiments described herein was determined to be 2 base changes out of 4485 bases, which is equivalent to an estimated error rate of less than or equal to 0.04%.

DNA sequence analysis was performed on four different open reading frames identified as genes and amplified by PCR methods from a dozen different strains of the bacterium Helicobacterpylori. The deduced amino acid sequences of three of the four open reading frames that were selected for this study showed statistically significant BLAST homology to defined proteins present in other bacterial species. Those ORFs included: Protein 26054702, homologous to the val A B genes encoding an 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, an outer membrane receptor in iron (III) dicitrate transport in E. coli. Protein 346 was identified as an unknown open reading frame, because it showed low homology with sequences in the public databases.

To assess the extent of conservation or variance in the ORFs across various strains of H. pylori, changes in DNA sequence and the deduced protein sequence were compared to the DNA and deduced protein sequences found in the J99 strain of H.

pylori (see Table 10 below). Results are presented as percent identity to the J99 strain of n. pytori sequenced by random shotgun cloning. To control, for any variations in the J99 sequence each of the four open reading frames were cloned and sequenced again from the J99 bacterial strain and that sequence information was compared to the sequence information that had been collected from inserts cloned by random shotgun sequencing of the J99 strain. The data demonstrate that there is variation in the DNA sequence ranging from as little as 0.12 difference (Protein 346, J99 strain) to approximately 7% change (Protein 26054702, strain AH5). The deduced protein sequences show either no variation Protein 346, strains AH 18 and AH24) or up to as much as 7.66% amino acid changes (Protein 26054702, Strain WO 98/24475 PCTIUS97/22104 -96- Table Multiple Strain DNA Sequence analysis of H. pylori Vaccine Candidates J99 Protein 26054702 26054702 7116626 7116626 29479681 29479681 346 346 Length of Region Sequenced: 248 a.a. 746 nt. 232 a.a. 96 nt. 182 a.a. 548 nt. 273 a.a. 819 nt.

Strain Tested J99.

AH244 AH4 AH61 5155 5294 7958 5640 AH18 AH24 AA Nuc. AA Nuc. AA Nuc. AA Nuc.

identity identity identity identity identity identity identity identity 100.00% 100.00% 100.00% 100.00% 100.00% 100.00% 99.63% 99.88% 95.16% 95.04% n.d. n.d. 99.09% 96.71% 98.90% 96.45% 95.97% 95.98% 97.84% 95.83% n.d. n.d. 97.80% 95.73% 92.34% 95.16% n.d.

n.d.

94.35% 94.35% 95.16% n.d.

94.75% 93.03% 98.28% 94.91% 97.41% n.d. 97.84% n.d. n.d.

94.37% 98.28% 94.10% 97.84% 94.37% 97.41% n.d. 98.71% 95.04% 97.84% 96.12% 95.98% 95.98% n.d.

95.40% 95.40% 95.69% 95.69% 95.40% 98.91% 99.82% 99.27% 99.45% 99.64% n.d.

99.09% 99.64% 99.27% 96.90% 97.99% 97.44% 97.08% 97.26% n.d.

97.63% 97.44% 96.71% 98.53% 95.73% 99.63% 96.09% n.d. n.d.

98.53% 95.60% 97.07% 95.48% 99.63% 96.46% 98.53% 95.48% 100.00% 95.97% 100.00% 96.46% not done.

VI. Experimental Knock-Out Protocol for the Determination of Essential H. pylori Genes as Potential Therapeutic Targets Therapeutic targets are chosen from genes whose protein products appear to play key roles in essential cell pathways such as cell envelope synthesis, DNA synthesis, transcription, translation, regulation and colonization/virulence.

The protocol for the deletion of portions of H. pylori genes/ORFs and the insertional mutagenesis of a kanamycin-resistance cassette in order to identify genes which are essential to the cell is modified from previously published methods (Labigne- Roussel et al., 1988, J. Bacteriology 170, pp. 1704-1708; Cover et al.,1994, J. Biological WO 98/24475 PCTS97/22104 -97- Chemistry 269, pp. 10566-10573; Reyrat et al., 1995, Proc. Natl. Acad. Sci. 92, pp 8768-8772). The result is a gene "knock-out." Identification and Cloning ofH. pylori Gene Sequences The sequences of the genes or ORFs (open reading frames) selected as knock-out targets are identified from the H. pylori genomic sequence and used to design primers to specifically amplify the genes/ORFs. All synthetic oligonucleotide primers are designed with the aid of the OLIGO program (National Biosciences, Inc., Plymouth, MN 55447, USA), and can be purchased from Gibco/BRL Life Technologies (Gaithersburg, MD, USA). If the ORF is smaller than 800 to 1000 base pairs, flanking primers are chosen outside of the open reading frame.

Genomic DNA prepared from the Helicobacterpylori HpJ99 strain (ATCC 55679; deposited by Genome Therapeutics Corporation, 100 Beaver Street, Waltham, MA 02154) is used as the source of template DNA for amplification of the ORFs by PCR (polymerase chain reaction) (Current Protocols in Molecular Biology, John Wiley and Sons, Inc., F. Ausubel et al., editors, 1994). For the preparation of genomic DNA from H. pylori, see Example I. PCR amplification is carried out by introducing nanograms of genomic HpJ99 DNA into a reaction vial containing 10 mM Tris pH 8.3, mM KCI, 2 mM MgCI 2 2 microMolar synthetic oligonucleotide primers (forward=FI and reverse=R1), 0.2 mM of each deoxynucleotide triphosphate (dATP,dGTP, dCTP, dTTP), and 1.25 units of heat stable DNA polymerase (Amplitaq, Roche Molecular Systems, Inc., Branchburg, NJ, USA) in a final volume of microliters. The PCR is carried out with Perkin Elmer Cetus/GeneAmp PCR System 9600 thermal cyclers.

Upon completion of thermal cycling reactions, each sample of amplified DNA is visualized on a 2% TAE agarose gel stained with Ethidium Bromide (Current Protocols in Molecular Biology, John Wiley and Sons, Inc., F. Ausubel et al., editors, 1994) to determine that a single product of the expected size had resulted from the reaction.

Amplified DNA is then washed and purified using the Qiaquick Spin PCR purification kit (Qiagen, Gaithersburg, MD, USA).

PCR products a.e cloned into the pT7Blue T-Vector (catalog#69820-1, Novagen, Inc., Madison, WI, USA) using the TA cloning strategy (Current Protocols in Molecular Biology, John Wiley and Sons, Inc., F. Ausubel et al., editors, 1994). The ligation of the PCR product into the vector is accomplished by mixing a 6 fold molar excess of the PCR product, 10 ng of pT7Blue-T vector (Novagen), I microliter of T4 DNA Ligase Buffer (New England Biolabs, Beverly, MA, USA), and 200 units ofT4 DNA Ligase WO 98/24475 PCT/US97/22104 98 (New England Biolabs) into a final reaction volume of 10 microliters. Ligation is allowed to proceed for 16 hours at 16 0

C.

Ligation products are electroporated (Current Protocols in Molecular Biology, John Wiley and Sons, Inc., F. Ausubel et al., editors, 1994) into electroporationcompetent XL-1 Blue or DH5-a E.coli cells (Clontech Lab., Inc. Palo Alto, CA, USA).

Briefly, 1 microliter ofligation reaction is mixed with 40 microliters of electrocompetent cells and subjected to a high voltage pulse (25 microFarads, 2.5 kV, 200 ohms) after which the samples are incubated in 0.45 ml SOC medium yeast extract, 2% tryptone, 10 mM NaCI, 2.5 mM KCI, 10 mM MgCl 2 10 mM MgSO 4 and mM glucose) at 37°C with shaking for 1 hour. Samples are then spread onto LB (10 g/1 bacto tryptone, 5 g/l bacto yeast extract, 10 g/l sodium chloride) plates containing 100 microgram/ml of Ampicillin, 0.3% X-gal, and 100 microgram/ml IPTG. These plates are incubated overnight at 37 0 C. Ampicillin-resistant colonies with white color are selected, grown in 5 ml of liquid LB containing 100 microgram/ml of Ampicillin, and plasmid DNA is isolated using the Qiagen miniprep protocol (Qiagen, Gaithersburg, MD, USA).

To verify that the correct H.pylori DNA inserts had been cloned, these pT7Blue plasmid DNAs are used as templates for PCR amplification of the cloned inserts, using the same forward and reverse primers used for the initial amplification of the J99 H.pylori sequence. Recognition of the primers and a PCR product of the correct size as visualized on a 2% TAE, ethidium bromide stained agarose gel are confirmation that the correct inserts had been cloned. Two to six such verified clones are obtained for each knock-out target, and frozen at -70 0 C for storage. To minimize errors due to PCR, plasmid DNA from these verified clones are pooled, and used in subsequent cloning steps.

The sequences of the genes/ORFs are again used to design a second pair of primers which flank the region of H pylori DNA to be either interrupted or deleted (up to 250 basepairs) within the ORFs but are oriented away from each other. The pool of circular plasmid DNAs of the previously isolated clones are used as templates for this round of PCR. Since the orientation of amplification of this pair of deletion primers is away from each other, the portion of the ORF between the pr;mers is not included in the resultant PCR product. The PCR product is a linear piece of DNA with H. pylori DNA at each end and the pT7Blue vector backbone between them which, in essence, resultes in the deletion of a portion of the ORFs. The PCR product is visualized on a 1% TAE, ethidium bromide stained agarose gel to confirm that only a single product of the correct size has been amplified.

WO 98/24475 PCT/S97/22104 -99- A Kanamycin-resistance cassette (Labigne-Roussel et al., 1988 J. Bacteriology 170, 1704-1708) is ligated to this PCR product by the TA cloning method used previously (Current Protocols in Molecular Biology, John Wiley and Sons, Inc., F.

Ausubel et al., editors, 1994). The Kanamycin cassette containing a Campylobacter kanamycin resistance gene is obtained by carrying out an EcoRI digestion of the recombinant plasmid pCTB8:kan (Cover et al.,1994, J. Biological Chemistry 269, pp.

10566-10573). The proper fragment (1.4 kb) is isolated on a 1% TAE gel, and isolated using the QIAquick gel extraction kit (Qiagen, Gaithersburg, MD, USA). The fragment is end repaired using the Klenow fill-in protocol, which involved mixing 4ug of the DNA fragment, 1 microliter of dATP,dGTP, dCTP, dTTP at 0.5 mM, 2 microliter of Klenow Buffer (New England Biolabs) and 5 units of Klenow DNA Polymerase I Large (Klenow) Fragment (New England Biolabs) into a 20 microliter reaction, incubating at 0 C for 15 min, and inactivating the enzyme by heating to 75 0 C for 10 minutes. This blunt-ended Kanamycin cassette is then purified through a Qiaquick column (Qiagen, Gaithersburg, MD, USA) to eliminate nucleotides. The overhang is then generated by mixing 5 micrograms of the blunt-ended kanamycin cassette, 10 mM Tris pH 8.3, mM KCI, 2 mM MgCl 2 5 units of DNA Polymerase (Amplitaq, Roche Molecular Systems, Inc., Branchburg, NJ, USA), 20 microliters of 5 mM dTTP, in a 100 microliter reaction and incubating the reaction for 2 hours at 37 0 C. The "Kan-T" cassette is purified using a QIAquick column (Qiagen, Gaithersburg, MD, USA). The PCR product of the deletion primers (F2 and R2) is ligated to the Kan-T cassette by mixing to 25 ng of deletion primer PCR product, 50 75 ng Kan-T cassette DNA, 1 microliter 1 Ox T4 DNA Ligase reaction mixture, 0.5 microliter T4 DNA Ligase (New England Biolabs, Beverly, MA, USA) in a 10 microliter reaction and incubating for 16 .2 hours at 16uC.

The ligation products are transformed into XL-1 Blue or DH5-a E.coli cells by electroporation as described previously. After recovery in SOC, cells are plated onto LB plates containing 100 microgram/ml Ampicillin and grown overnight at 37 0 C. These plates are then replica plated onto plates containing 25 microgram/ml Kanamycin and allowed to grow overnight. Resultant colonies have both the Ampicillin resistance gene present in the pT7Blue vector, .md the newly introduced Kanamycin resistance gene.

Colonies are picked into LB containing 25 microgram/ml Kanamycin and plasmid DNA is isolated from the cultured cells using the Qiagen miniprep protocol (Qiagen, Gaithersburg, MD, USA).

Several tests by PCR amplification are conducted on these plasmids to verify that the Kanamycin is inserted in the H. pylori gene/ORF, and to determine the orientation of the insertion of the Kanamycin-resistance gene relative to the H. pylori gene/ORF. To WO 98/24475 PCTI~S97/22104 100verify that the Kanamycin cassette is inserted into the H. pylori sequence, the plasmid DNAs are used as templates for PCR amplification with the set of primers originally used to clone the H. pylori gene/ORFs. The correct PCR product is the size of the deleted gene/ORF but increased in size by the addition of a 1.4 kilobase Kanamycin cassette. To avoid potential polar effects of the kanamycin resistance cassette on H.

pylori gene expression, the orientation of the Kanamycin resistance gene with respect to the knock-out gene/ORF is determined and both orientations are eventually used in H.

pylori transformations (see below). To determine the orientation of 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:255)), and "Kan-2" 5'-AGACAGCAACATCTTTGTGAA-3' (SEQ ID NO:256)). By using each of the cloning primers in conjunction with each of the Kan primers (4 combinations of primers), the orientation of the Kanamycin cassette relative to the H.pylori sequence is determined. Positive clones are classified as either in the orientation (the same direction of transcription is present for both the H pylori gene and the Kanamycin resistance gene), or in the orientation (the direction of transcription for the H.pylori gene is opposite to that of the Kanamycin resistance gene). Clones which share the same orientation (A or B) are pooled for subsequent experiments and independently transformed into H. pylori.

Transformation ofPlasmid DNA into H. pylori cells Two strains of H. pylori are used for transformation: ATCC 55679, the clinical isolate which provided the DNA from which the H pylori sequence database is obtained, and A-244,, an isolate which had been passaged in, and has the ability to colonize the mouse stomach. Cells for transformation are grown at 37 0 C, 10% CO 2 100% humidity, either on Sheep-Blood agar plates or in Brucella Broth liquid. Cells are grown to exponential phase, and examined microscopically to determine that the cells are "healthy" (actively moving cells) and not contaminated. If grown on plates, cells are harvested by scraping cells from the plate with a sterile loop, suspended in 1 ml of '3rucella Broth, spun down (1 minute, top speed in eppendorf microfuge) and resuspended in 200 microliters Brucella Broth. If grown in Brucella Broth liquid, cells are centrifuged (15 minutes at 3000 rpm in a Beckman TJ6 centrifuge) and the cell pellet resuspended in 200 microliters of Brucella broth. An aliquot of cells is taken to determine the optical density at 600 nm, in order to calculate the concentration of cells.

An aliquot (1 to 5 OD 600 units/25 microliter) of the resuspended cells is placed onto a prewarmed Sheep-Blood agar plate, and the plate is further incubated at 37 0 C, 6% CO 2 WO 98/24475 PCTfUS97/22104 101 100% humidity for 4 hours. After this incubation, 10 microliters of plasmid DNA (100 micrograms per microliter) is spotted onto these cells. A positive control (plasmid DNA with the ribonuclease H gene disrupted by kanamycin resistance gene) and a negative control (no plasmid DNA) are done in parallel. The plates are returned to 37 0 C, 6% CO 2 for an additional 4 hours of incubation. Cells are then spread onto that plate using a swab wetted in Brucella broth, and grown for 20 hours at 37 0 C, 6% CO 2 Cells are then transferred to a Sheep-Blood agar plate containing 25 micrograms/ml Kanamycin, and allowed to grow for 3 to 5 days at 37 0 C, 6% CO2, 100% humidity. If colonies appear, they are picked and regrown as patches on a fresh Sheep-Blood agar plate containing micrograms/ml Kanamycin.

Three sets of PCR tests are done to verify that the colonies of transformants have arisen from homologous recombination at the proper chromosomal location. The template for PCR (DNA from the colony) is obtained by a rapid boiling DNA preparation method as follows. An aliquot of the colony (stab of the colony with a toothpick) is introduced into 100 microliters of 1% Triton X-100, 20 mM Tris, pH and boiled for 6 minutes. An equal volume of phenol chloroform is added and vortexed. The mixture is microfuged for 5 minutes and the supernatant is used as DNA template for PCR with combinations of the following primers to verify homologous recombination at the proper chromosomal location.

TEST 1. PCR with cloning primers originally used to amplify the gene/ORF. A positive result of homologous recombination at the correct chromosomal location should show a single PCR product whose size is expected to be the size of the deleted gene/ORF but increased in size by the addition of a 1.4 kilobase Kanamycin cassette. A PCR product of just the size of the gene/ORF is proof that the gene had not been knocked out and that the transformant is not the result of homologous recombination at the correct chromosome location.

TEST 2. PCR with F3 (primer designed from sequences upstream of the gene/ORF and not present on the plasmid), and either primer Kan-1 or Kan-2 (primers designed from the ends of the kanamycin resistance gene), depending on whether the plasmid DNA used was of"A" or orientation. Homologous recombination at the correct chromosomal location will result in a single PCR product of the expected s;ze from the location of F3 to the insertion site of kanamycin resistance gene). No PCR product or PCR product(s) of incorrect size(s) will prove that the plasmid had not integrated at the correct site and that the gene had not been knocked out.

TEST 3. PCR with R3 (primer designed from sequences downstream of the gene/ORF and not present on the plasmid) and either primer Kan-1 or Kan-2, depending on whether the plasmid DNA used was of or orientation. Homologous WO 98/24475 PCT/US97/22104 -102recombination at the correct chromosomal location will result in a single PCR product of the expected size from the insertion site of kanamycin resistance gene to the downstream location of R3). Again, no PCR product or PCR product(s) of incorrect size(s) will prove that the plasmid had not integrated at the correct site and that the gene had not been knocked out.

Transformants showing positive results for all three tests above indicate that the gene is not essential for survival in vitro.

A negative result in any of the three above tests for each transformant indicates that the gene had not been disrupted, and that the gene is essential for survival in vitro.

In the event that no colonies result from two independent transformations while the positive control with the disrupted ribonuclease H plasmid DNA produces transformants, the plasmid DNA is further analyzed by PCR on DNA from transformant populations prior to plating for colony formation. This will verify that the plasmid can enter the cells and undergo homologous recombination at the correct site. Briefly, plasmid DNA is incubated according to the transformation protocol described above.

DNA is extracted from the H. pylori cells immediately after incubation with the plasmid DNAs and the DNA is used as template for the above TEST 2 and TEST 3. Positive results in TEST 2 and TEST 3 would verify that the plasmid DNA could enter the cells and undergo homologous recombination at the correct chromosomal location. If TEST 2 and TEST 3 are positive, then failure to obtain viable transformants indicates that the gene is essential, and cells suffering a disruption in that gene are incapable of colony formation.

VII. High-throughput drug screen assay Cloning, expression and protein purification Cloning, transformation, expression and purification of the H. pylori target gene and its protein product,e.g., an H. pylori enzyme, to be used in a high-throughput drug screen assay, is carried out essentially as described in Examples II and III above.

Development and application of a screening assay for a particular H. pylori gene product, peptidyl-propyl cis-trans isomerase, is described below as a specific example.

Enzymatic Assay The assay is essentially as described by Fisher (Fischer, et.al. (1984) Biomed.

Biochim. Acta 43:1101-1111). The assay measures the cis-trans isomerization of the Ala-Pro bond in the test peptide N-succinyl-Ala-Ala-Pro-Phe-p-nitroanilide (Sigma S- 7388, lot 84H5805). The assay is coupled with a-chymotrypsin, where the ability of the protease to cleave the test peptide occurs only when the Ala-Pro bond is in trans.

The conversion of the test peptide to the trans isomer in the assay is followed at 390 nm WO 98/24475 PCT/US97/22104 -103 on a Beckman Model DU-650 spectophotometer. The data are collected every second with an average scanning of time of 0.5 second. Assays are carried out in 35 mM Hepes, pH 8.0, in a final volume of 400 ul, with 10 iM ac-chymotrypsin (type 1-5 from bovine Pancreas, Sigma C-7762, lot 23H7020) and 10 nM PPIase. To initiate the reaction, 10 pl of the substrate (2 mM N-Succinyl-Ala-Ala-Pro-Phe-p-nitroanilide in DMSO) is added to 390 l1 of reaction mixture at room temperature.

Enzymatic assay in crude bacterial extract.

A 50 ml culture of Helicobacterpylori (strain J99) in Brucella broth is harvested at mid-log phase (OD 600 nm 1) and resuspended in lysis buffer with the following protease inhibitors: 1 mM PMSF, and 10 pg/ml of each of aprotinin, leupeptin, pepstatine, TLCK, TPCK, and soybean trypsin inhibitor. The suspension is subjected to 3 cycles of freeze-thaw (15 minutes at -70 0 C, then 30 minutes at room temperature), followed by sonication (three 20 second bursts). The lysate is centrifuged (12,000 g x 30 minutes) and the supernatant is assayed for enzymatic activity as described above.

Many H. pylori enzymes can be expressed at high levels and in an active form in E. coli. Such high yields of purified proteins provide for the design of various high throughput drug screening assays.

VIII. Truncated gene expression and protein production Identification, cloning and expression ofrecombinant Helicobacter pylori sequences.

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

PCR amplification and cloning ofDNA sequences containing ORFsfor membrane and secreted proteins from the J99 strain ofHelicobacter pylori.

The sequences chosen (from the list of the DNA sequences of the invention) for cloning from H. pylori strain J99 were prepared for amplification cloning by the polymerase chain reaction (PCR). Synthetic oligonucleotide primers for the ORF of interest (Table 11) specific for the predicted mature 5' end of the ORF and either WO 98/24475 PCT/US97/22104 -104downstream of the predicted translational termination codon or at specific points within the coding region were designed and purchased (GibcoBRL Life Technologies, Gaithersburg, MD, USA). All forward primers (specific for the 5' terminus of the region of ORF of interest) were designed to include either a BamHI or a NdeI restriction site. These primers within the NdeI restriction site sequence were designed to permit the initiation of protein translation at a methionine residue (encoded within the NdeI restriction site sequence, in the case of producing a non His-tagged recombinant protein) or to fuse in frame with the DNA sequence encoding the His-tag (for producing His tagged recombinant protein), followed by the coding sequence for the remainder of the native H. pylori DNA. The primer with the BamHI restriction site was produced to fuse the H. pylori specific sequence in-frame with the C-terminus of the glutathione-Stransferase gene in the pGEX vectors (Pharmacia LKB, Uppsala, Sweden). All reverse oligonucleotide primers designed to include an EcoRI restriction site at the 5' terminus.

Several reverse oligonucleotide primers were selected that would cause a truncation of the polypeptide to remove certain portions of the C-terminus, and in these cases the EcoRI restriction site at the 5' end was followed by a translational termination codon.

This combination of primers would enable the ORF of interest (or parts of the ORF of interest) to be cloned into pET28b (to produce a His-tagged recombinant protein), (to produce a non His tagged or native recombinant protein) or the pGEX-4T or pGEX-5X series (to produce a GST fusion protein). The pET28b vector provides sequence encoding an additional 20 amino-terminal amino acids (plus the methionine in the NdeI restriction site) including a stretch of six histidine residues which makes up the His-tag, whereas the pGEX vectors fuse the H. pylori protein to a 26,000Da glutathione- S-transferase protein.

Genomic DNA prepared from H. pylori strain J99 (ATCC 55679) was used as the source of template DNA for the PCR amplification reactions (Current Protocols in Molecular Biology, John Wiley and Sons, Inc., F. Ausubel et al., eds., 1994). To amplify a DNA sequence containing a specific H. pylori ORF, genomic DNA nanograms) was introduced into a reaction tube containing 200 nanograms of both the forward and reverse synthetic oligonucleotide primer specific for the ORF of interest, and 45 microliters of PCR SuperMix purchased (GibcoBRL Life Technologies, Gaithersburg, MD, USA) in a total of 50 microliters. The PCR SuperMix is supplied in 1.1X concentrations and contains 22mM Tris-HCl (pH 55mM KC1, 1.65mM MgCl2, 220 micromolar of each dATP, dCTP, dGTP and dTTP, 22units recombinant Taq polymerase/ml and stabilizers. The following thermal cycling conditions were used to obtain amplified DNA products for each ORF using a Perkin Elmer Cetus/GeneAmp PCR System thermal cycler.

WO 98/24475 PCT/US97/22104 -105- Table 11: Oligonucleotide primers Gene and location Sequence Vac38- BamHI post signal sequence CGGGATCCGAAGGTGATGGTGTTTATA TAGG (SEQ ID NO: 271) Vac38- Ndel post signal sequence CGCATATGGAAGGTGATGGTGTTTATA TAGGG (SEQ ID NO: 272) Vac38- EcoRl/stop codon (removes C- GCGAATTCTCACTCTTTCCAATAGTTTG terminal third of protein) CTGCAGAGC (SEQ ID NO: 273) Vac38- EcoRI/stop codon (removes C- CCGGAATTCTTAATCCCGTTTCAAATG terminal 11 amino acids) GTAATAAAGG (SEQ ID NO: 274) Vac38- EcoRl downstream of native stop GCGAATTCCCTTTTATTTAAAAAGTGT codon AGTTATACC (SEQ ID NO: 275) Sequences for Vac38 (full length or truncated) Denaturation at 94 0 C for 30 sec cycles at 94 0 C for 15 sec, 55 0 C for 15 sec, and 72 0 C for 1.5 min Reactions were concluded at 72 0 C for 8 minutes Upon completion of the thermal cycling reactions, each sample of amplified DNA was subjected to electrophoresis on 1.0% agarose gels. The DNA was visualized by exposure to ethidium bromide and long wave UV irradiation, and cut out in gel slices. DNA was purified using the Wizard PCR Preps kit (Promega Corp., Madison WI, USA), and then subjected to digestion with Bamili and EcoRI (Current Protocols in Molecular Biology, John Wiley and Sons, Inc., F. Ausubel et al., eds., 1994). The digested PCR amplicon was then re-electrophoresed and purified as before.

Ligation ofH. pylori DNA sequences into cloning vectors The pOK12 vector Vieira and J. Messing, Gene 100:189-194, 1991) was prepared for cloning by digestion with BamHI and EcoRI or NdeI and EcoRI in the case of Vac41 (Current Protocols in Molecular Biology, John Wiley and Sons, Inc., F.

Ausubel et al., eds., 1994). The vectors were subjected to electrophoresis on agarose gels and purified using the Wizard PCR Preps kit (Promega Corp., Madison WI, USA). Following ligation of the purified, digested vector and the purified, digested SUBSTITUTE SHEET (RULE 26) WO 98/24475 PCTIUS97/22104 -106amplified H. pylori ORF, the products of the ligation reaction were transformed into E.

coli JM 109 competent cells according to standard methods (Current Protocols in Molecular Biology, John Wiley and Sons, Inc., F. Ausubel et al., eds., 1994). Individual bacterial colonies were screened for those containing the correct recombinant plasmids by incubating in LB broth overnight (plus 25ug/ml kanamycin sulfate) followed by plasmid DNA preparation using the Magic Minipreps system (Promega Corp., Madison WI, USA), and then analyzed by restriction digestion (Current Protocols in Molecular Biology, John Wiley and Sons, Inc., F. Ausubel et al., eds., 1994).

Cloning ofH. pylori DNA sequences into the pET28b, pET30a andpGEX4T-3 prokaryotic expression vectors Both the pET28b and pET30a expression vectors were prepared for cloning by digestion with NdeI and EcoRI, and the pGEX4T-3 vector was prepared for cloning by digestion with BamHI and EcoRI (Current Protocols in Molecular Biology, John Wiley and Sons, Inc., F. Ausubel et al., eds., 1994). The H. pylori DNA sequences were removed from pOK12 plasmid backbones by digestion with NdeI and EcoRI or BamHI and EcoRI (Current Protocols in Molecular Biology, John Wiley and Sons, Inc., F.

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

Transformation of competent bacteria with recombinant expression plasmids Competent bacterial strains BL21 (DE3), BL21 (DE3)pLysS, HMS 174(DE3) and HMS 174(DE3)pLysS were prepared and transformed with the recombinant pET28b expression plasmids carrying the cloned H. pylori sequences according to standard methods (Current Protocols in Molecular Biology, John Wiley and Sons, Inc., F.

Ausubel et al., eds., 1994). These expression host strains contain a chromosomal copy of the gene for T7 RNA polymerase. These hosts are lysogens of bacteriophage DE3, a lambda derivative that carries the lac gene, the lacUV5 promoter and the gene for T7 WO 98/24475 PCT/US97/22104 -107- RNA polymerase. T7 RNA polymerase expression is induced by the addition of isopropyl-p-D-thiogalactoside (IPTG), and the T7 RNA polymerase then transcribes any taget plasmid, such as pET28b, that carries a T7 promoter sequence and a gene of interest.

Competent bacterial strains JM109 and DH5a were prepared and transformed with the recombinant pGEX4T-3 expression plasmid carrying the cloned H. pylori sequences according to standard methods (Current Protocols in Molecular Biology, John Wiley and Sons, Inc., F. Ausubel et al., eds., 1994).

Expression ofrecombinant H. pylori sequences in E. coli Transformants were collected from LB agar plates containing kanamycin sulfate (ensures maintenance of the pET28b-based recombinant plasmids) or 100ug/ml ampicillin (ensures maintenance of the pGEX4T-3-based recombinant plasmids) and used to inoculate LB broth containing 25ug/ml kanamycin sulfate or 100ug/ml ampicillin and grown to an optical density at 600nm of 0.5 to 1.0 OD units, at which point ImM IPTG was added to the culture for one to three hours to induce gene expression of the H. pylori recombinant DNA constructions. After induction of gene expression with IPTG, bacteria were pelleted by centrifugation and resuspended in SDS- PAGE solubilization buffer and subjected to SDS-PAGE (Current Protocols in Molecular Biology, John Wiley and Sons, Inc., F. Ausubel et al., eds., 1994). Proteins were visualized by staining with Coomassie Brilliant Blue or detected by western immunoblotting using the specific anti-His tag monoclonal antibody (Clontech, Palo Alto, CA, USA) or the anti-GST tag antibody (Pharmacia LKB) using standard methods (Current Protocols in Molecular Biology, John Wiley and Sons, Inc., F. Ausubel et al., eds., 1994). The host strain that provided the highest level of recombinant protein production was then chosen for use in a large-scale induction in order to purify the recombinant protein. The strains used were HMS174(DE3) (pET28b-based constructs) and DH5a (pGEX4T-3-based constructs).

Removal of the C-terminal regions appeared in both systems to improve the level of expression, although this increase was far more prominent in the GST-fusion system.

All recombi'iant proteins produced were of the predicted molecular weight based on the DNA sequence plus, if necessary, the size of the fusion tag. The truncated portion of the H. pylori protein contains some extremely hydrophobic stretches, and removal of these may be the reason for the increased expression.

-108-

EQUIVALENTS

Those skilled in the art will recognize, or be able to ascertain using no more than routine experimentation, many equivalents to the specific embodiments and methods described herein. Such equivalents are intended to be encompassed by the scope of the following claims.

With reference to the use of the word(s) "comprise" or "comprises" or "comprising" in the foregoing description and/or in the following claims, we note that unless the context requires otherwise, those words are used on the basis and clear understanding that they are to be interpreted inclusively, rather than exclusively, and that we intend each of those words to be so interpreted in construing the foregoing description and/or the following claims.

WO 98/24475 PCT/US97/22104 -109- SEQUENCE LISTING 1) GENERAL INFORMATION:

APPLICANT:

NAME: Astra Aktiebolag STREET: S-151 CITY: Sodertalje

STATE:

COUNTRY: Sweden POSTAL CODE (ZIP) (ii) TITLE OF INVENTION: NUCLEIC.ACID AND AMINO ACID SEQUENCES RELATING TO HELICOBACTER PYLORI AND VACCINE COMPOSITIONS THEREOF (iii) NUMBER OF SEQUENCES: 275 (iv) COMPUTER READABLE FORM: MEDIUM TYPE: CD/ROM ISO9660

COMPUTER:

OPERATING SYSTEM:

SOFTWARE:

CURRENT APPLICATION DATA: APPLICATION NUMBER FILING DATE: (vi) PRIOR

(A)

(B)

(vii) PRIOR

(A)

(B)

(viii) PRIOR

(A)

(B)

APPLICATION DATA: APPLICATION NUMBER:US 08/759,625 FILING DATE: 05-DEC-1996 APPLICATION DATA: APPLICATION NUMBER: US 08/823,745 FILING DATE: 25-MAR-1997 APPLICATION DATA: APPLICATION NUMBER: US 08/891,928 FILING DATE: 14-JULY-1997 (ix) CORRESPONDENCE ADDRESS: ADDRESSEE: LAHIVE COCKFIELD STREET: 28 State Street CITY: Boston STATE: Massachusetts COUNTRY: USA ZIP: 02109-1875 ATTORNEY/AGENT INFORMATION: NAME: Mandragouras, Amy E.

REGISTRATION NUMBER: 36,207 REFERENCE/DOCKET NUMBER: GTN-011CP2PC (xi) TELECOMMUNICATION INFORMATION: WO 98/24475 PTU9/20 PCT/US97/22104 -110- TELEPHONE: (617)227-7400 TELEFAX: (617)227-5941 INFORMATION FOR SEQ ID NO:1: Ci) SEQUENCE CHARACTERISTICS: LENGTH: 687 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc-feature LOCATION .687 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:l:

ATGAGATTTA

GAATATGAAG

TTGTTCATTT

GGCGAATTGT

GAATCCCTTT

TTAATCATTT

GAAACCACCA

AAAGAAGAAT

ACAGAGCGTT

GAAAGAGTAA

AGGATTTATA

CAAAGGATAA

AGGGTTCAAG

AGTTTAAAGA

CTTGCGTGGA

ATGTGATCCG

CTACCATTGC

GCGGGCATAG

AAGCTAAAAC

TAAAAAACCA

TGAATGCGCG

TAAATAACGA

ATTATAATTT

GTCATGAAAA

AGTGGAAGCG

GCTTTATGAG

TTCACGAGTC

CAACATGGGC

GAGCGTTGAA

CGATTGTGGG

CCCTTACATT

CCCGCAATTC

CTTGCAACTC

ATTAAAAATT

TGAAAGCCAT

CTTCTAA

TTTTTAGGAG

AGCTTAAAAA

GTGCCTAATT

AATGTGATCC

TACGCTATCG

GCTTGCGGGA

GCAAACTGGA

AGCAACCATT

AACAACCTCT

TTTGGTTGGC

TTTTTTGAGC

CGTTAGAATT

CCAAGCAAAA

TAATCACAGG

CCCCTAAAAC

CGCATGTGGG

GCATTCATTT

TACAATTTTT

TCGCCAAGCG

TAAGCTATGA

ACTATATCAT

CGATTGAAGA

TCAAGAGAAT

GCCCCACACT

CACCCAACCG

AAGCTATAAA

CGTTCAAAAC

AATCCATGAT

AGAGCCTATT

TTCATGGCTT

TTTCATTCAA

AGAAACAGGC

AACCATTAAA

INFORMATION FOR SEQ ID NO:2: Ci) SEQUENCE CHARACTERISTICS: LENGTH: 666 base pairs TYPE: nucleic acid STRANDEDNESS; double TOPOLOGY: .i:cular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: WO 98/24475PCUS7214 PCTfUS97/22104 -1III- ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc-feature LOCATION I1.. .666 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:2:

GTGGAAGCGT

CTTTATGAGA

TCACGAGTCG

AACATGGGCA

AGCGTTGAAT

GATTGTGGGG

CCTTACATTG

CCGCAATTCA

TTGCAACTCA

TTAAAAATTT

GAAAGCCATT

TTCTAA

TTTTAGGAGC

GCTTAAAAAC

TGCCTAATTT

ATGTGATCCC

ACGCTATCGC

CTTGCGGGAG

CAAACTGGAT

GCAACCATTT

ACAACCTCTT

TTGGTTGGCA

TTTTTGAGCC

GTTAGAATTT

CAAGCAAAAG

AATCACAGGC

CCCTAAAACA

GCATGTGGGC

CATTCATTTA

ACAATTTTTA

CGCCAAGCGT

AAGCTATGAT

CTATATCATA

GATTGAAGAA

CAAGAGAATG

CCCCACACTT

ACCCAACCGG

AGCTATAAAG

GTTCAAAACT

ATCCATGATG

GAGCCTATTA

TCATGGCTTA

TTCATTCAAG

GAAACAGGCA

ACCATTAAAC

AATATGAAGA

TGTTCATTTC

GCGAATTGTA

AATCCCTTTC

TAATCATTTG

AAACCACCAA

AAGAAGAATT

CAGAGCGTTT

AAAGAGTAAT

GGATTTATAA

AAAGGATAAG

GTTTAAAGAG

TTGCGTGGAT

TGTGATCCGC

TACCATTGCG

CGGGCATAGC

AGCTAAAACC

AAAAAACCAC

GAATGCGCGC

AAATAACGAA

TTATAATTTT

TCATGAAAAC

120 180 240 300 360 420 480 540 600 660 666 INFORMATION FOR SEQ ID NO:3: SEQUENCE CHARACTERISTICS: LENGTH: 1008 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc-feature LOCATION .1008 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:3: ATn1TTAGTTA CTCGTTTTAA AAAAGCCTTC ATTTCTTATT

ATTATTAT

GGGGAGCAAA

GTGCCTGCCA

GATGACATTG

ACCGATCATA

GTAACCTTTG

CTTTCTTTCC

GTCTTAGAAA

GCTGAGCGTT

TGAATGTGTG

CCATAA.AGCT

TGCTTAATGT

TCAAAGCCAC

CAGCCGCGTT

TGGGTAACCC

AAGAGACAAC

TTGACGCTTC

TGAAGGGCGT

CAACGCTTCA

TCCTGTTTCC

TTGGGATAGG

TCTCAAAGGC

GAATGTGGAA.

TAAAGCGGTA

GATTGCAGAG

CAAAAAATTC

TAAAAAGAAA

GCACAAGAAG

AAAATAGCCT

GTTGTAGGCG

GAGGATCTTA

TTATTAAAAA

GAGCATGCGA

GCCATGCAAG

GCCAAAATGC

AAGGGGGTGG

CTTTAGGCGT

TCAAAGTCAA

ATATAGGGAG

TTTCTGATTA

AACGAGTCAA

AGCTTAGCCC

AAAAATTTGG

CTATGCAAGC

AAGAAACTTT

AGCTTTTCCA

GCTTGTTGTT

GGATTATTTT

TTATGTAGAA

TGCCTTTAAG

ACACATGAGC

TGATCTTGTG

GATTTCATTC

TCAAGCCACG

GGACTTTATT

TAAAGCCAAT

120 180 240 300 360 420 480 540 600 WO 98/24475 PCTIUS97/22104 -112-

AAAATCAGCG

TTTGGCTTGA

GAAAACCCTG

AACAACCCTA

ACGATGGATA

CACCCTGAAG

GTCTTTGATT

GCCATCAAGC

AATACGTTAA

AAATCATTTT

AATTTTCCAC

TTGGCGGTCC

CCTTTAAAGG

TGAATGATGC

CATTAGCTCA

GTTTGGACGC

CATTTGGTGG

TATCAAAGCC

TAGAGCCCCA

CGTGGATATT

GGAAATTGAG

GACATTTTAG

GCTGACATTA

GTAAGCCCAC

ATTAAAAATA

CTCATTAGTC

AATGCGATAG

CCATTCTTAT

AAAAAGGGGG

GTGTGGAAAA

TCACTCCTGA

AGCAAGTCTA

TTTTTATCGC

TCAAAGATTA

GGCACTGA

TATAGATAAT

AATCGTTAAA

AGACGTGTTG

TAAGCTCCCC

TTTAAAAGC C

TTATAAAGTG

660 720 780 840 900 960 1008 INFORMATION FOR SEQ ID NO:4: SEQUENCE CHARACTERISTICS: LENGTH: 825 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NANE/KEY: misc-feature LOCATION .825 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:4:

ATGTTAGTTA

TCATTATTAT

GGGGAGCA~A

GTGCCTGCCA

GATGACATTG

ACCGATCATA

GTAACCTTTG

CTTTCTTTCC

GTCTTAGAAA

GCTGATCGTT

AAAATCAGCG

TTTGGCTTGA

GAAAACCCTG

AACAACCCAA

CTCGTTTTAA

TGAATGTGTG

CCATAAAGCT

TGCTTAATGT

TCAAAGCCAC

CAGCCGCGTT

TGGGTAACCC

AAGAGACAAC

TTGACGCTTC

TGAAGGGCGT

GCCATCAAGC

AATACGTCAA

AAATCATTTT

AATTTTCTAC

AAAAGCCTTC

CAACGCTTCA

TCCTGTTTCC

TTGGGATAGG

TCTCAAAGGC

GAATGTGGAA

TAAAGCGGTA

GATTGCAGAG

CAAAAAATTC

TAAAAAGAA

CATTAACTCA

GTTTGGACGC

ATTTCTTATT

GCACAAGAAG

AAAATAGCCT

GTTGTAGGCG

GAGGATCTTA

TTATTAAAAA

GAGCATGCGA

GCCATGCAAG

GCCAAAATGC

AAGGGGGTGG

GACATTTTAC

GCTGACATTA

CTTTAGGCGT

TCAAAGTCAA

ATATAGGGAG

TTTCTGATTA

AACGAGTCAA

AGCTTAGCCC

AAAAATTTGG

CTATGCAAGC

AAGAAACTTT

AGCTTTTCCA.

AACAAGGGGG

GTGTGGAAAA

TCACTCCTGA

TATAA

GCTTGTTGTT

GGATTATTTT

TTATGTAGAA

TGCCTTTAAG

ACACATGAGC

TGATCTTGTG

GATTTCATTC

TCAAGCCACG

GGACTTTATT

TAAAGCCAAT

TATTGATAAT

AATCGTTAAA

TTACGTGTTG

120 180 240 300 360 420 480 540 600 660 720 780 CATTAGGTGG GTAACCCCAC TATCAATGCC ATTAAAAACA INFORMATION FOR SEQ ID Wi SEQUENCE CHARACTERISTICS: LENGTH: 1287 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular WO 98/24475 PTU9/20 PCT[US97/22104 -113- (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc-feature LOCATION .1287 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:

ATGAAGAAAA

GAAGACAACG

AAAAACACCA

ACGAATTATA

AACGCAAGGG

CCGGCGTATC

AGCTATGCGA

ACTTTCCACA

GGTTATGAAC

GCTTATCAAA

GACACCAACA

AATAATGGAG

ACCATTATAA

GCGAGTAGTG

ATTTTTAAAA

GAGCAATCCA

ACATTCAACC

CAAGCGGAGA

GAGTTCGTAA

ACGCCATCCG

ACCGTAmkACGA

AACGCGCGCA

AATTTCTGTC

GCTTTTTTGT

AAGGCATTCA

GCGTCCTAAA

GCAATTTGAA

AAGCCGTGCT

TCAGCCCTTG

ACACGCCTTC

CAGGACCATA

TCATCCAAAA

CAGAACTCAA

AAGAAATTGT

CTACCCTTAA

GTAGTTTATG

ATGAAATCAG

AGATCGTTGC

CCTATAAAGA

TTTTAAACCG

AAGACTCTTT

GCACGGTAAC

A T CT AA-AAG A

ACCTCGCTAC

ATTAACCTTA

GAGCGCCGGC

AGATCTTTCA

CGCTCTCATC

CGCGAGCGCG

TTTAGCCTTG

TGGTCCCGGT

AAATCAATGG

CAGCATTTTA

GGCTTTTGGG

ATTCACAATC

TACAAAAAAT

TAGCGCATGC

GGAAGGAATA

CGCGATTCAA

TGCAAACGCG

CGCCAACTTC

CGCCCAAGCA

AGGGGTGTGC

TGATAACACT

CAGCATCGCT

ACTTTAG

GGTTCGCTTT

TATCAAATCG

GACAGCTATG

AGGCAGTCCG

AAGAATTTGA

AATGCGGCAG

AAAGACACAA

GGAGGCACTA

TCCACTGAAA

AGCAGCGGAA

AATAAAAATA

AACGCTCAAG

CCATGGATCA

TATTTGAAAG

GACATGATCA

CAAAACCAGC

GCCCAAAGCA

GTGGTGAXAG

CATGAAGTGC

TGGGGAGCCG

CATTTTGGCG

TAGTTTCCGC

GTGAATCCGC

AAAGATTGAA

CCGACCCCAA

TCAATGATAA

CGGGGTTGTG

GCAAAAATGG

CCATTACTTG

ATTACGCGAA

AAGATATTCC

ATGGAAACAC

TTCTTTTAGA

ACAATGGTGG

GCGATGGGAG

AAAACGCTGC

GCAACCTAGA

TGTTCGCTAA

ACTTTGAAAG

AAAACGGCCA

GTTGCGCGTA

ACCAAGCCGA

TTTAAGCGCT

TCAAATGGTG

CAACCTTTTA

CGCCATCAAT

AAAGAATTCC

GCAAGTCATG

GGGCGTTCAA

TGGCACTACT

AATCAATAAA

TGCCTTAAGC

GAATACGAAT

ACAGGCTAGC

TGCAGGTGGT

CGCTTGCGGG

AATAGCCGTA

CACCGGGAAG

CGCCAAAGCG

AATCCCTGCA

TCTCCGTGGC

TGTGGGAGAG

GCGAATCCAT

120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1140 1200 1260 1287 INFORMATION FOR SEQ ID NO:6: SEQUENCE CHARACTERISTICS: LENGTH: 537 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) *(iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori WO 98/24475 PTU9/20 PCTIUS97/22104 -114- (ix) FEATURE: NAME/KEY: misc-feature LOCATION .537 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:6:

ATGAACCCCT

TTGAGCGGCG

TTAGAATTTG

GCTATCCCTT

AAAAGAGCGG

ATTAAAAAGC

GCGGTCGCTA

TATTTTTTAT

TGCTTTATGC

TATTGCAAGA

CGAGAAATTT

TCAAAGATTT

TAGCCCTTGA

CTTTTTTAAA.

GTTTAGAAGA

GCTCTTCTTT

TCTATAAAGG

ATCAAAAGCG

TTATGCGCGC

AAGCGAATTA

TAAAAGCTGC

AAAACCTGAA

CTACCTTAAA

TTATCAAAAT

TTTGATAGAA

CGAGCAGTTA

CGTTTATTTT

ATCCTTTTAG,

GAACCCCAGA

TTGGATATTG

GCGCAATTCA

AGCGTTTTGC

CTTTTACAAG

AAAAGCCAAC

AAGAATGAAA

TACAAATCAA

AATGGAATCA

TCACAGACGC

GGAGCGGGGC

TTCTTTTAGA

CTTTAAACAA

TGGATTTAAT

GCTTCCTAAA

TCGCTTATAA

AGGAAAGTTT

AACGCACAAC

TCTAAAGCCC

GGGACTTCCT

GCCAAGGGTA

CATTGAAATC

CACTTCTAGA

AGATAAGGGG

AACCACTGAA

ATGTTAA

120 180 240 300 360 420 480 537 INFORMATION FOR SEQ ID NO:7: SEQUENCE CHARACTERISTICS: LENGTH: 723 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pyloni (ix) FEATURE: NALME/KEY- misc-feature LOCATION .723 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:7:

TTGGGTCTTA

GCGCTTGATT

TATGAAGATA

GGGCTTATTT

AATAGCTCCA

GGCTATCAAA

AGGCGCATCT

GGGTTTCAAT

GGGAAATACC

GTGAATTATA

GAAAAAAACC

AATTCTTCAA

TAA

AAAAACGAGC

ATGACACCCT

AAGAAGTTGA

TAGGGATCAA

GTATCACC3G CTTTC. .3 CC

ATATTCAATA

CGGTCATGTT

TTTATATGGG

CGGCGGAATG

GCATTGAATT

AAGAGACTTG

TATTTTATGG

AGACCCAAAA

AGAATTGATC

TACCGGTTTT

GAATATTTTA

GTCGTTTTTT

TTATGGAGGA

GAATGGGGAT

GGGGTATATG

GGGGATGTCT

TGAATTTAAA

GTGGGGAGCT

TCTTTAATGG

TATTACAAAT

AGAGACTTGA

TTTTATAACC

AATTATTTGT

GCGCGCTTGG

GCTCCTAAGA

TTTTTATTAG

GGTTTAGGCT

TTTAACGCAG,

ATTTTGAATA

ATAGCAAGCA

GATTTTGTGC

ATATCAAGTA

AAAGGGCGAA

ATGAAATCAT

TCGCCTATGG

TTAAGCCCAA

AAGCGGGCTT

ACTTTCCTTT

TGGGGGTTGT

GATTGGCTCT

ATTTCCCTTT

TTGGGTATCA

AGGATTGAGC

TTATAAGGCT

CGCTAAAAGC

GGTCAAAACC

CTTGCGTTTT

TATCATTGGC

TGGGAGCGTG

GCCCTTTGTG

GGCGCATGGG

AACGGTATTA

TTTGCAATCT

ATATGTGTTC

120 180 240 300 360 420 480 540 600 660 720 723 WO 98/24475 PTU9/20 PCTIUS97/22104 115- INFORMATION FOR SEQ ID NO:8: SEQUENCE CHARACTERISTICS: LENGTH: 942 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pyloni (ix) FEATURE: NAME/KEY: misc feature LOCATION .942 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:8:

TTGAAACTCA

TATGACAATT

CAGCTCACCG

TATTTAGAGC

TTTTCCATAG,

CTTAACTTGT

TTTAAAAACA

CAAAAATACT

GGGGCGTTA.A

GCTATGAATA

TTAGGCGTTT

AACGGGAGGA

ATTGAAGTGG

TTAGAGATTG

ATTTATCACA

CGATCCAGTT

AATACTGGTT

TAGAAGAAGA

AAAAAGGGGT

GAACTTACCC

CCGATGATAA

CTTATCAAGG

ATATCAATAT

TCGTGCCTTA

AAGAGAACGC

CCGATTTATT

ATGCGGGTTT

ATTTGATAGT

ATTACACTTT

GCACAAAATT

ATAAAGAAAA

TTTTATTAGT

AGTTTATCTG

AAACCAACAA

TTCACCCAAA

AAAGATTTCT

GAGTGGGGTG

GGAGATGTTA

TAACGCTCCT

TTTTGGGACA

GCTCAAGCAG

GTTTGACATG

TGGGATAGGG

AGGGGGTTAT

TAATGTGGGC

ACCGATTAGC

TGATGAACGA

GAATTATGCG

GCGTTCATTA

TTAGACGAAA

GAGATGGATA

TCAAAGAAAA

TTTTTAGGGG

GACAGGTATG

GTTTCTATGA

CGATTTTATG

CCTGTAGGCT

CCTTTAGATT

CTTATGCTTT

TCAAGCCCTA

GTGAGTTTAA

TATTTGAGGA

TTGTTGATTT

TTCATTTTTT

TAGGACTTCA

AAATAAACAA

AGGATAAGTT

GAAAAAAATT

GCGGGTATGC

GCGCAAATGC

TTAGCGTTAA

GGGATTTGTT

CGTTTTTTTA

TTAAGACTAA

ATCAAGACAA

ATTTTTTATG

CGCTTTATAG

TGGGAGTAGA

CGGCTAACAA

GA

AGCGACAGAT

TTTAAAGCGA

TGAAGAAGAA

GCTCAAATCT

TTATGGGGAA

CCCTAGCGCG

ATTTGGGTAT

GCTTGGGGGA

TGTTTTAGGG

AAAGCATTTT

GCCTAATCAA

GAAATCTTTG,

GAAACACCGC

AGAGGGAGCG

CCAGTTCAAA

120 180 240 300 360 420 480 540 600 660 720 780 840 900 942 INFORMATION FOR SEQ ID NO:9: Wi SEQUENCE CHARACTERISTICS: LENGTH: 1182 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO WO 98/24475 PTU9120 PCTIUS97/22104 -116- (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc-feature LOCATION .1182 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:9:

ATGACTTCAG

GCTTTTGATA.

ATCGCTAAAG

GAAGAAGATA

GAAGTAAAAG

ACCAAGCGTT

TATTCTAAAA

TTCTTAAACA

CCGTATGAAG

AAAATATTAG

TGTCGTTCAA.

CTTTCTGAAG

GCCCTAAGAG

TGGACATATC

TTTATGAGCG

CATTACTACC

CAGATTGCCC

ATTCCCCAA

TTTATTAGTA

CAACTCAAGC

CTTCAAGCCA

AGAATTATCT

CCAATAAAAA

AAACAAAACT

ATATTGAACC

TTTCTAAAAT

TGGTGTGGAG

TTAAAGAAGA

GCTTTTTTTA

AAATCATACG

AGATCGCGCC

AGCATTTAAA

AACCTATCGT

CTTTTGGTTT

ATTGGTCTTA

ATGGCATTGC

ATGACGCTCT

ACGCAAGGCG

AAACCCTTAA

TCTTAAAAAA

TTCTTTTAA.A

CATTCCTGCG

AA.TCCGTTAC

TAACCAAATC

TTTTTTAGAC

GGTGTTAGTG

CGATGTGGAT

TGATGAGAAT

TTGCAACTTA

CGCACAAAAA

ATTAAAAATA

GGGCGTGGCC

TATACAATAT

GAAAGCGGAT

TTTGATCACA

CGCTTATCAT

TAAGACATTT

AAGACTATTC

ATTTCTAAAA

GAACCAGAGC

GAACAAGATT

GGCGCATGCA

ACCTTACACG

ACAGAGCCTT

ACTATCCCTA

AAGTATTTTC

GTTATCTTTT

TATTTTTATG

ACTTACCAGC

ATAGATAAAG

GAGTATTGTA

AATGCAATTT

GACTCTCATC

TTATGGCTGA

GGGGGTGGGG

TACTACTTTC

TTAAAACATT

AAATACTGCA

CTCCATGCAT

CAAAACTTTT

TTCATATTCC

TTTATTCCTT

CTTTAGTGGT

TTAAAGAATT

ACCCTTTTGA

TAGCGGATTT

GTAATGAATT

GGGTTTATGA

GAAAAAATCA

AACCGCAATT

TTTTCCCACA.

ATCATAACAC

CTTATTTTCA

ACGCTTTGGC

GGATAGGTGG

CTTTATGGAA

ATTTTTTGCA

TTTCAATACC

TGGTGAAAAA

AA

TATCGCTTTC

GCTAGAAAGC

AGGCTTGAAT

TGCTGTTTTA

TGAGGATTTC

ATTCCCCAAA

TAGCGCTGAT

CAAAATATAC

ATTTTGTAAA

GACAGAATTT

CTATTATAGC

CATTAAACAA

AATCAAGCCT

TAAAACCCCA

AGAAAAATGG

AGCAGAAGAA

CATTCATGAG

GCTTAAGAGC

AATCCTAATC

120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1140 1182 INFORMATION FOR SEQ ID SEQUENCE CHARACTERISTICS: LENGTH: 1308 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pyloni (ix) FEATURE: NAME/KEY: misc-feature LOCATION .1308 (xi) SEQUENCE DESCRIPTION: SEQ ID TTGATTTTCT TAAAAAAATC TCTTTGCGCG TTGTTAATTT CAGGTTTTTT CATACCACCC WO 98/24475 PTU9/20 PCTIUS97/22104 117- TTAATGAAAG CGGCTAGTTT TGTCTATGAC TTGAAGTTTA TGAGCTTTAA

GCTTCCCCTC

CCTCAAATTG

CAAAATTTGC

CAATACATAG

GGGCATTACC

GGAGGAGCGT

GAGGGCGTTG

TACGATTTTG

TTAGGTTTGG

AACTACCCTT

AATGGCTACC

TCTAACCCTA

AATCTCATGC

CATTATTGCG

GGGGAATTTT

TCCAACAAAC

CCATGGTATA

TGGTTAAGCG

TTGTATGGCA

GACACAAGAG

CAAATAACCC

GCGTCCAATT

ACACGCATTA

GGAAAAATTT

CTTTAAGCGC

TCCAATTCAA

TGGATTGGTA

ATCAATTCTT

GGGGACAGCT

ATGGCGGGAA

CTTATTTCAG

CCATTTTAGA

CTTATATGGA

TGCGTTATGC

ACGCTCAAGC

CCCAAATGCA

GAGCCCCTAA

TGCGAGCGGA

AGGGGGGTAA

AGTTGATTGA

CTATTGGAAT

AGACPAAAAGA

TAGCTATTTC

GAGATTTTTT

TTTTAAAAAA

ACCGGCTTAT'

TGGGGGGCGT

GTATTTTGTT

TGTCATTTTT

TTCCTACTTA

CCAAAAAGAT

CAGGGTTTAT

CAATATTTTC

TAGCGAGTGT

GCAATACAAA

TTTTTATGCC

TTTTGACATG

TGCGTTTTTT

GTGGTTTGTG

TTTTGTCAA.A

AGCCTAACCA

CAGGCCTTGA

CCTTATTCGT

TTAGGCATTG

CTTTTCTGGT

GATCCCAATC

AATTGGAACA

TCTTCAGAAT

CATAACGCCA

AAACCAGGCG

AACCCACAAG

TACCATGCTT

ATGACCTTTG

AAAAACGCCC

GGCTTTGGGA

ACTTATGGCC

ATAGGGCTTT

AGCTTTGTGG

ATGTATCAGC

TCTAAA.ATCC

AAATGCAAGG

TGTTTGGGGC

GGGGGGTTAC

TGCCACGAAG

TTATAGACCC

GTTGGTGGAA

ACCAGCCCAA

TTCAGTTTCT

ACTCTCATAG

ATGCAACCCC

GCGGAGAAAT

ATTTAAAAGC

GCACGCAGTC

GATTTTATAA

TCTTTAACAG

AATCCCTTTA

ATTATCTTTA

GTGGGGGCGA

AATTTTTAAC

CTAAATAA

TTTCAATCTG

TCGTCTCATG

GTGGTTCATT

CATGTATTAC

CTATCAAATA

TACTTTTAGG

TGGGTGGTTT

AAAGAAAAAT

TAAAGGGTAT

TATGGGGGAT

ACAATGGCCT

AGGGAAATAC

AGATTTTAAA

GTCTCAAACC

CAGCTTTGGG

ATACTATTTT

TACCGGATTG

TAAAAACAAA

TGGGTACCAT

CCTAACCATA

120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1140 1200 1260 1308 INFORMATION FOR SEQ ID NO:11: Ci) SEQUENCE CHARACTERISTICS: LENGTH: 663 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) Ciii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1 .663 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:11:

ATGAATAAAA

GCAGAGGCAG

TATTTAGGGG

GATAAATCGT

GCTAAAACGC

TTTTCTTCTC

GCTTTCAATT

ACTTACATGC

TCGCTTTTCC

CAACAATTAA

AGCTTGATGA

TTGGGTATCA

ATTTCATGAC

AAGCTGTAGA

ACAAATCCTA

CGCCAAAGAT

CAGGAGGGGC

AATTGCTTGT

AATATTAATG

AAAATCAAAA

GCTTAGCGCG

CGGCAATGGT

GCATGTGGGT

TATTTCTACC

GTTTTTGGGG

CATGCATGGG

GAAAGTGGGT

c-c LTGGCGT

AAACCTAAAT

ATCAACACGT

TTTGGCGTGG

TTTCGTTACG

TATGGTTTAG

TTGGAGTTTG

ATTATCGCTC

TTTCGTTTTG

TATTATCATC

TTGCGGATAG

CTTTTAGCAC

TGTTGGGGGG

GGTTGTTTTA

AATTTAGCGG

GCTTAGGCAT

AATATTTAGG

GCTTTTTCC.A

GCTTCAAGCC

GAATACGTTT

CAGTTCTATA

GAAATTTGTG

TGATCAGACC

TTTGTGGGAC

CGCTGGGGCG

CAAAGAAAAT

CAATGAAATC

120 180 240 300 360 420 480 540 WO 98/24475 PCT/US97/22104 -118- ACCTTTGGGT TGAAATTCCC TGTCATTCCT AACAAAAAAA CGGAAATCGT TGATGGCTTG AGCGCGACCA CTTTATGGCA ACGCTTGCCG GTAGCCTATT TCAATTATAT CTATAATTTT

TAG

INFORMATION FOR SEQ ID NO:12: SEQUENCE CHARACTERISTICS: LENGTH: 351 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...351 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:12: TTGAATCTCC ATTTTATGAA AGGATTTGTT ATGAGTGGAT GTGGTTTTAT GCGGTGCAAT GGTTAATGTA GCTGTAGCTG GGTGAATTAG GCAAATTTGT AGGGGGAGCT GTTGGAAATT GGATTTGTTG GTGGTGCAAT AGGAGGATAT ATTGGGTCTG GATTATATCC GTGGCGTTGA TAGAGAGCCA CAAAACAAAG CCTATCCGTG ATTTTTATGA TTACGGCTAT AGTTTTGGGC INFORMATION FOR SEQ ID NO:13: SEQUENCE CHARACTERISTICS: LENGTH: 1311 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPDTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc_feature LOCATION 1...1311 TAAGAACATT TAGTTGTGTA GTCCTAAAAT AGAGGCAAGG

TTGTTGGTGA

AAGTAGGCGA

AACCACAAAC

ATGCTTGGTG

TAAAATGGGC

TAGGGTAGAA

CCCAAGAGAA

120 180 240 300 351 WO 98/24475 PTU9/20 PCT/US97/22104 -119- (Xi) SEQUENCE DESCRIPTION: SEQ ID NO:13:

ATGTCAAGGG

GGCCCCGTTT

TATGTGATGA

CAAACTTTTA

AGCACATGCG

TCTAAAACGC

GATAAAATAG

TTGAACTATA

CAGCGTCAA

ATATGGTATG

ACTAGGACTA

AAAAATTAT

GGAGGCTATA

TACGCGCCGA.

ACTTCTAACG

ATTAAAGGGA

ACTTACAAGC

ATGCTCAATC

GGGTTAAAGT

CAAGTAAGCT

AATAACCTTT

GAACCCGCGC

ATTTTAAATT

ATACCAATCA

ACGCTTTTGA

ATGTGGGCAT

AAAAAACAGA

CTAACAATAA

AGTTTTTTGA

ACAACAAAGA

ACGAATGGAG

CGAACTACCG

ATTACAACCA

TGAGTTTTAA

GCCCACAGCC

TTAGGGGTTT

CTGATGATAT

AGCGCTTGCC

ACACGACTTT

AAGCCAAAGA

ATGGTTGTAA

CAATCTTATG

TTAACATGAA

TGATTCTAAC

AAATTATCCA

GCCTAATTTG

GCGTTTTATG

TATTATCAAT

TCAAGAAATG

TTCTAAATTG

GCCAGAAAAG

TCCTGCCCTT

CCGCAGTTTT

AATTTTTAAT

CACCAATTAT

TGTGGATGCC

GCAATTCCAT

TGCTTATTAT

CTATGTGAGT

TGGTATCAGC

TCAAACCGTA

TTCAGTGGGG

GCAAAGCGGT

GTATTATTTT

TATTTAAATG

GGATTTTTTA

AACTTAGTTG

ACAATGGATA

GGGGTGTGCC

TTTAATAACT

GTGATAACTC

CATGATTTTT

AATATTGGCT

ATCCCCCCAC

GAAATTGAAG

TTTGTGATTT

AGAAGTCAAG

GTGGCTTACA

TTTACAGGCA

CCTAACCAAT

AGCTATTTTT

TGCCTGCCCT

TTATTGCCCT

AGGCATAAAA

AGGGGGATTG

TCAATACCAA

TCTTTGATCA

TCAATACCAA

TGTTCATTAG

ACATGCCTCC

ATACAGCGGT

CAGGGCTTAG

CCGTATGGAC

ATAAACCTAT

AACACACAAT

TGGGGCAGCG

TTGCCAAGCG

GGGTGGAATT

CTTATATTGA

TTGTCAATAA

TCATATTTGA

ATAGCCGCGC

TAAACCCAGA

TGTATTTTGT

TCACAGGGAG

GCACAAGCCC

ATGAGTTTTA

TCCTAAATTA

TTTAAGGCGT

TAAAGTTAAG

ATCCGATCAA

TTATGTCCTT

ATGGTTGAGC

ATACACTTTT

CAGTAAAAAA

GGAAAATTGG

GGTAGGCATT

CTATAGTTAT

TTACTATGCG

GGAATTGTAT

TGCGCGCATC

ACCCTTTGAC

CATGATGTAT

TTATAGTTCC

ATACACAGGG

GTTGAATGTC

TTTGCAA.ATC

TACAGGGAGA.

A

120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1140 1200 1260 1311 CAGGGAGATC CATTACAGCG TATTTGAATT INFORMATION FOR SEQ ID NO:14: SEQUENCE CHARACTERISTICS: LENGTH: 2304 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1 .2304 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:14: ATGAAAkAGAA

CATAATTTGG

TGGAGGAGCA

CTCACTAAAA

ATTAGAAACT

TTTTAGTTTC

AAAGGGTGGA

AGGAAGTTAG

GCGCCAATCA

CTACCGGTAT

TTTGGCTGTT

AGCTTCAGGG

AAATTATATG

AAGCATTGAA

TGGAGCTGTG

TTGAGTCATA

GTGGCTAACG

GGTTCTCGCA

GAAGCTTTGC

CCTAGCATTT

GCGCGCATGC

ATAAAGAAGC

CGGTGATTTC

AAAATGTGCC

CCATTAGGGG

TGTCAAAACT

GCCTTTAAGC

TAACAAGCAA

AGGCGTGCAT

GTTTGGTGCT

120 180 240 300 WO 98/24475 WO 9824475PCTIUJS97/22104 120

GGAGGCCCAG

GCGCCCTATG

ATCAGCGTAA

ATCAACATCA

ACTTTTTGGG

AAAAGCTTAG

AAGCATTTTG

AGCCCTACGG

AAAATCACCG

ATAGCCGCTT

AGAGCGAAGC

GGGGATTTCA

AACTATTTAA

CCAGGATTTT

TTGAACTTAG

ATGACAATGG

AATGGGGTGT

ATGTTTAATA

TTGGTGATAA

AAGCATGATT

CTTAATATTG

TTTATCCCCC

AATGAAATTG

TATTTTGTGA

GCCAGAAGTC

CATGTGGCTT

TATTTTACAG

AGTCCTAACC

AGCAGCTATT

GTATGCCTGC

GGGTTATTGC

GGTAGGCATA

TTTAGGGGGA

GCGTATTTGA

GGCATTCTAA

TTGAAATTGG

CTAAGGGTGG

TCACCAAAGG

GCAAGTCTGA

TTAATAACAT

GAATCCAAGC

ATATTCAAAA

CTTTTTTTCA

ACAATCAAAA

GATGGGGAGC

CTTTTAGCTA

ATGTCAATAC

TTATCTTTGA

TTGTCAATAC

ATATGTTCAT

GCCACATGCC

ACTATACAGC

CTCCAGGGCT

TTTCCGTATG

GCTATAAACC

CACAACACAC

AAGTGGGGCA

TTTTTGCCAA

AAGGGGTGGA

ACACTTATAT

GCATTGTCAA

AATTCATATT

TTTATAGCCG

CCTTAAACCC

CCTTGTATTT

AAATCACAGG

TTGGCACAAG

ATTATGAGTT

TACGGGAATG

CACGGTTATT

GGAGAGCGTG

CATTCCTACC

AAACGGGGGC

GCTTTTTAAC

TCAAGTCAAT

TTACATGTTA

ATATTATAGT

TCGTTTTCAA

TGTGTATCAA

CTATGGGCAT

CAATCCTAAA

TCATTTAAGG

CAATAAAGTT

TAGATCCGAT

TCCTTATGTC

GGTATGGTTG

TAGATACACT

GACCAGTAAA

TATGGAAAAT

AATGGTAGGC

GCGCTATAGT

GCGTTACTAT

ATTGGAATTG

TGATGCGCGC

TAAACCCTTT

TGACATGATG

CGCTTATAGT

AGAATACACA

TGTGTTGAAT

GAGTTTGCAA

CCCTACAGGG

TTAA

ATTCTAGTCA

TTTCCTGTAA

CGTTATGGCC

AATTGGGAAA

TTTTTCAATC

ACCTATTTAA

TGGCTCAAAG

GATTCATTGT

TATTTCTTGA

AACAACCGCC

AACTTTTTTG

GACATGTCAA

TTAGGCCCCG

CGTTATGTGA

AAGCAAACTT

CAAAGCACAT

CTTTCTAAAA

AGCGATAAAA

TTTTTGAACT

AAACAGCGTC

TGGATATGGT

ATTACTAGGA

TATAAAAATC

GCGGGAGGCT

TATTACGCGC

ATCACTTCTA

GACATTAAAG

TATACTTACA

TCCATGCTCA

GGGGGGTTAA

GTCCAAGTAA

ATCAATAACC

AGAGAACCCG

ATGGGATTCC

CCTTTCAGTC

CTAACGCTTT

GTCAGGTGAG

AAAATTCTAA

GAACGGGGGG

GGCAAGGGTT

ATCAAATCAA

CAGACCCTGG

CCAATAACGA

GGGACACGGA

GGGATTTTAA

TTTATACCAA

TGAACGCTTT

TTAATGTGGG

GCGAAAAAAC

CGCCTAACAA

TAGAGTTTTT

ATAACAACAA

AAAACGAATG

ATGCGAACTA

CTAATTACAA

TATTGAGTTT

ATAGCCCACA

CGATTAGGGG

ACGCTGATGA

GGAAGCGCTT

AGCACACGAC

ATCAAGCCAA

AGTATGGTTG

GCTCAATCTT

TTTTTAACAT

CGCCAGGGAG

TATTTATGTC

TGTGGATAGA

TGGCGGTGTG

CGAGAGGACC

AAACATTGAT

TATGATGAAT

TAGATACAAC

TGATAGCAAT

ATCTTTAGGC

TAAAAGCGGG

TAGGGTAGGG

ATTTGATTCT

TCAA.AATTAT

TGAGCCTAAT

CATGCGTTTT

AGATATTATC

TAATCAAGAA

TGATTCTAAA

AGAGCCAGAA

GAGTCCTGCC

CCGCCGCAGT

CCAAATTTTT

TAACACCAAT

GCCTGTGGAT

TTTGCAATTC

TATTGCTTAT

GCCCTATGTG

TTTTGGTATC

AGATCAAACC

TAATTCAGTG

ATGGCAAAGC

GAAGTATTAT

ATCCATTACA

360 420 480 540 600 660 720 780 840 900 960 1020 1080 1140 1200 1260 1320 1380 1440 1500 1560 1620 1680 1740 1800 1860 1920 1980 2040 2100 2160 2220 2280 2304 INFORMATION FORP SE) ID SEQUENCE CHARACTERISTICS: LENGTH: 348 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature WO 98/24475 WO 9824475PCTIUS97/22104 121 LOCATION .348 (xi) SEQUENCE DESCRIPTION: SEQ ID

TTGCACCCTC

ATTAGCGTGG

GCGCTAGATG

GACTGGTGGT

GCTTTAAACT

ATCAAAGATT

TATGCGCACA

GGATTGTGCC

AACGATCGTT

TAGAAAACAA

ACACTTTAGA

TTAAAAACAA

CGGCCAATGT

TGTTATCGCT

ATTTGAGCCT

ACTTGAAAGA

AAATTCAGTC

CCCCAACCTC

GGAAGCGAAG

AATAGCCCTT

AATAACGCTA

GAAAGAATGC

ATTCAAATTG

TTTAAAACCT

CGATTGCGTG

TAAGCGCGAC

AAGATTTGAG

AAAACGAATA

AAAAAGTTTA

TATCGTAA

TTTAGAAGCC

CAGGCAATTC

CGCTAAAATA

CGCTAAAAGC

TGAAGAAGCG

INFORMATION FOR SEQ ID NO:16: Wi SEQUENCE CHARACTERISTICS: LENGTH: 1170 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION .1170 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:16:

ATGGTTATTG

GCGTTTCGTT

CATGTGGATA

CCCCTAGTTA

ATTCTACGAA

GAAAAAACAG

TTACAGCCAG

ATGCTTTTTT

TCAAAATTCA

TCTAACGGCT

ACGCCCTTTA

ATTAAAGCGG

GGGCCTGATG

GGGTTTGTCA

ACGGCCAATG

CCTGTTATCG

TTATTTGAGC

AAACTTGAAA

GAAAATTCAG

AACCCCAACC

TTTTAGTCGT_

TTTTTGAAGC

ATTTAGGGAG

CAGAAATTTC

AGGCTTTTAA

CCGTAAAAAT

AGCATATTTC

CATGGTTTAA

TTGTAGAAGA

TTGATCCCAT

AAATCGCTAT

TTGCTTTAAG

AGAAAAAAAT

ATTCCCATGA

TGGAAAGCGA

CTAATAGCCC

CTAATAACGC

GAGAAAGAAT

TCATTCAAAT

TCTTTAAAAC

GGATAGCTTT

GCTGAAAAAA

TGAAGAAGAG

ACACAAGCAA

GGGAGCGGAT

CGCGCGAGAA

TTATAACATG

ATCTTCGCAT

ATTGGAAAAA

GTTTAAGTTT

GGTAGGC2GC CCGAA AAA

CAAACTTCTA

ATTGTTAGAG

AGCGATTGCG

TTTAAGCGCG

TAAAGATTTG

GCAAAACGAA

TGAAAAAGTT

CTTATCGTAA

AAAGACACCA

AGAGGGCATG

GGGTATTACA

CACATTCTTT

ATGATCCATA

ATGCGAGTGC

AAATTGGGGC

TACCGCTATA

TACAACTATG

GAGCACCCGC

TATTCTAATG

CAAGACATTG

GCCCAAAAAC

ATTTTAAAAA

TGTTTAGAAG

ACCAGGCAAT

AGCGCTAAAA

TACGCTAAAA

TATGAAGAAG

GTAATGGCAC

CGATGAGAGT

ACCTTAAAGA

TTGCCAAACC

CTTACTTGCC

CTTATATTGG

AATTTTCTTG

TCCACCATAT

GAGGAAAAAA

AAAAAAGCCT

AAAAAAATCA

TATTATTACT

TAGGCGTAAA

CTTGCACCCT

CCATTAGCGT

TCGCGCTAGA

TAGACTGGTG

GCGCTTTAAA

CGATCAAAGA

TTCTATGACA

GGTCGCCCCT

GCGCTATATC

GGATGAAAAA

TTTTTTGCTA

CTCTTTCCAT

GCTAAATACC

CCATTGCCCA

ATACGCTATC

TTTTGACACC

AAGCGTTCTC

CAAAGGCAAG

AACGGAGTTT

CTATGCGCAC

GGGGATTGTG

TGAACGATCG

GTTAGAAAAC

CTACACTTTA

TTTTAAAAAC

120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1140 1170 WO 98/24475 PCTITS97/22104 -122- INFORMATION FOR SEQ ID NO:17: SEQUENCE CHARACTERISTICS: LENGTH: 939 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc-feature LOCATION 939 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:17:

TTGGCTTCTT

TTACAGACTG

TTGGTTTTAG

TTGTTGATTT

GACGCTAAAA

CTTGTGATGT

CAAAAAAGCC

GTGGGGGGAG

TTAGACGCTC

CGTTTCTTAG

GCCTTAAGCT

TTCGCTCTGA

GCTACGCTCA

GTGGGAGGGG

GAATCGAATC

ACGGGTTTTT

CCGGTAATCC

TCCAGGCGTT

TTAGCGCGAC

GCGTTCAAAT

ATCTTTTAAA

TGTTTTCGCA

AAGTGGCGAT

AATCAAGCGC

GCAGCGCTTT

CTATCATTCT

CTTTTGTGGG

ATTTAGGGCA

CGTTAATCCC

TGCTCTACGC

TTTAGGAGCG

CTTTGTAACC

CAATTCGCTT

CAAAACGAGC

GCCTTATTTG

ATTGCCTGAT

CAAACACTTT

TGGATCATTC

GCATTACTTG

GATGAATAAA

TATCGCTTTG

CTTTTTCAAC

TCTCACTTCT

CCCCATTCAA

TTATAGCGTG

TTGTTTATTT

TTGCTTTCTA

GGCACGACTT

GATAATTTAA

GGTTTAGCGG

GTGGAAAAAG

GTTTTTGGGG

TTGGTGCTAA

GTGTATTATT

ATCGCTCCTA

GCTATTCTTA

TCTATCATGT

AAGGCTTCTG

GGCGTGGTTA

CCGTTGTTGT

TAGCGAGCGG

AAGGTAAAGA

TAGGGCCTAT

GCCTGATAGA

TGTTTTCGCT

AAATGCCCAA

CTTTAGGGAT

GCTTTGAAAA

GGGGCGGCGC

ATAAATACCT

TTGGAGGCAA

TCCCTACAAT

GAGTGATTAG

CAGACATGCT

GCTATTTTTA

GATCGTGTGC

AGCCAGAAAC

TTTTGGGAGC

CAAGTTAGCG

TCTTTTAGCG

AGAAACGACG

CTTTTTCTAT

GCTTTTGAAT

GATGGTAGGG

GGCTTTCAAC

GATCGCTTTA

CTTTTCTTTG

CATGGCGATT

CACAGCAACC

TATCCTCTTC

120 180 240 300 360 420 480 540 600 660 720 780 840 900 939 TTTGCACTTA AGGGGTATAA ACAAGAAGAA AACTCCTAA INFORMATION FOR SEQ ID NO:18: SEQUENCE CHARACTERISTICS: LENGTH: 1224 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO WO 98/24475 PTU9/20 PCT[tJS97/22104 123 (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc-feature LOCATION .1224 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:18:

ATGCAAAAAA

GGTTTTATCA

ACCTATTTTG

GGAGTCTTTG

GTGATCACAG

TTTTTTTTAG

AATCCCTTTG

GCGTTCAATT

GCGACCAAAA

CAAATGCCTT

TTAAAATTGC

TCGCACAAAC

GCGATTGGAT

AGCGCGCATT

GCTTTGATGA

ATTCTTATCG

GTGGGCTTTT

GGGCATCTCA

ATCCCCCCCA

TACGCTTATA

TATAAACAAG

CTTCTAACAC

CGGTTTTAAA.

AAGCTTCGCT

GGAACGTGAT

CGAGCGGGTG

GAGCGTTGTT

TAACCTTGCT

CGCTTGGCAC

CGAGCGATAA

ATTTGGGTTT

CTGATGTGGA

AC!TTTGTTTT

CATTCTTGGT

ACTTGGTGTA

ATAAAATCGC

CTTTGGCTAT

TCAACTCTAT

CTTCTAAGGC

TTCAAGGCGT

GCGTGCCGTT

AAGAAAACTC

TTTAGCGCTG

CGACATTTTG

CATTCAATTT

CAGTAAAATC

CGCGTTGTTT

TATTTTAGCG

TTCTAAAGGT

GACTTTAGGG

TTTAAGCCTG

AGCGGTGTTT

AAAAGAAATG

TGGGGCTTTA

GCTAAGCTTT

TTATTGGGGC

TCCTAATAAA.

TCTTATTGGA

CATGTTCCCT

TTCTGGAGTG

GGTTACAGAC

GTTGTGCTAT

CTAA

GGGAGTTTGA

ATCCCGCATT

TGCTTTTTTG

GGCTACCCTT

TATCCGGCGG

AGCGGGATCG

AAAGAAGCCA

CCTATTTTTG

ATAGACAAGT

TCGCTTCTTT

CCCAAAGAAA

GGGATCTTTT

GAAAAGCTTT

GGCGCGATGG

TACCTGGCTT

GGCAAGATCG

ACAATCTTTT

ATTAGCATGG

CGGCGCTATT

TAAAGCCCAT

GGGCGTATTT

TTGGCGTGGT

CGCATTTTGG

TGTGCTTACA

GAAACTTGGT

GGAGCTTGTT

TAGCGGACGC

TAGCGCTTGT

CGACGCAAAA

TCTATGTGGG

TGAATTTAGA

TAGGGCGTTT

TCAACGCCTT

CTTTATTCGC

CTTTGGCTAC

CGATTGTGGG

CTTTCTAATG,

TTTTGACTTG

CATCATGGGG

GCTTGGTTTT

CTCTTACGGG

GACTGCCGGT

TTTAGTCCAG

GATTTTTAGC

TAAAAGCGTT

GATGTATCTT

AAGCCTGTTT

GGGAGAAGTG

CGCTCAATCA

CTTAGGCAGC

AAGCTCTATC

TCTGACTTTT

GCTCAATTTA

AGGGGCGTTA

GAATCTGCTC

ACTTAAGGGG

120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1140 1200 1224 ATGCTCACAG CAACCGAATC TTTTATATCC TCTTCTTTGC INFORMATION FOR SEQ ID NO:19: SEQUENCE CHARACTERISTICS: LENGTH: 378 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc-feature LOCATION .378 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:19: WO 98/24475 PTU9/20 PCT/US97/22104 -124-

ATGAATAAAA

ATCGCTTTGG

TTTTTCAACT

TCACTTCTAA

CCCATTCAAG

TATAGCGTGC

CAAGAAGAAA

TCGCTCCTAA

CTATTCTTAT

CTATCATGTT

TGGCTTCTGG

GCGTGGTTAC

CGTTGTTGTG

ACTCCTAA

TAAATACCTG

TGGAGGCAAG

CCCTACAATC

AGTGATTAGC

AGACATGCTC

CTATTTTTAT

GCTTTCGGCG

ATCGCTTTAT

TTTTCTTTGG

ATGGCGATTG

ACAGCAACCG

ATCCTCTTCT

CCTTAAGCTC

TCGCTCTGAC

CTACGCTCAA

TGGGAGGGGC

AATCGAATCT

TTGCACTTAA-

TATCATTCTT

TTTTGTGGGC

TTTAGGCATC

GTTAATCccc

GCTCTACGCT

GGGGTATAAA

120 180 240 300 360 378 INFORMATION FOR SEQ ID Wi SEQUENCE CHARACTERISTICS: LENGTH: 993 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NANE/KEY: misc feature LOCATION 1 .993 (xi) SEQUENCE DESCRIPTION: SEQ ID,

TTGAAAAAAA

TTGTTAGAAA

GATTCTTATT

TTTGGCTATT

GAGTTTTATG

GGCTCTAAAA

CGTATCACGC

AATTACCCTA

GGAATGCCTT

AACCCTATTC

TATGAAGACA

TTCCAATGGA

CCCAATTTCA

GTGTTTGCAA

CCCAACTCTC

CAGCAAAACA

AACAATCAAG

TATTACCGGC

TCATGCGCCT

TAGCGGATAA

ATCAAAACAA

AAATAGAAAA

AGGGCGATAA

AGAAATTAGA

ATTTGTATGA

TAAATGGCGA

TAAGCTCTTA

AGTTTTCCCC

AAGAAGCTTG

CTCGCTATGA

AAAATGAAAA

AAAACAAACG

AGCTCTCTTA

CGTCTATTAT

TTTGTTAATG

TTATCAAAAA

GTCTTTTTGG

GCAGTTTTTA

TAACATGCTT

AACTTTAGAG

GCGTTTGGAT

CACTTTGAAA

TAGGAATGAA

TGACAAAGTG

TAGCACTAAA

GGCTAGGGGC

CGGCATGAGT

AAAGAATATC

CTTGTTTTAT

TAGCTCCAAT

AATGGAAAAA

GGGTTTGTGG

CAAGGCTTGG

GCAGAAGAGC

TTTGTGGCGG

AAAAAAATCA

GGCGATTTGG

CAATATTATG

AAACGCACCG

TTGAACACTA

TTAAAAGGCG

GAAGAATTGA

GATTTTGAAC

TTTAACGCTT

GCTTTTTCCT

GTGGTATTTG

TCTCAAAAAG

TAA

GATTGAATGC

AAGTGGTGGG

TTCAAAACAA

ATAAATCCAA

ACAGCTCTAA

CCACGCCTAT

GCGTTTTGGC

GGCATGGCAT

AGGGTTGCAT

AAAAAGCGTT

GCATGATTTT

GCTACATGCG

TT tAAGAGTA

C'.ATCAATGT

ACCAAGATTA

AACTCTATGT

TAGTGATCGT

TCAAAAATTG

GGACACGGAT

GCCCAGTTTG

AGCCCTTGTA

TGGAGTGTAT

TTTTGTAACG

TTGGGTGCAT

TGCGATTGAA

CCTTATCACT

AAGCTCCCTT

TTTTTATAAC

TAAAAAAAGG

GATCCCTTAC

CAAAGCCTAC

AGAGATTGAA

120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 993 INFORMATION FOR SEQ ID NO:21: SEQUENCE CHARACTERISTICS: LENGTH: 510 base pairs WO 98/24475 WO 9824475PCTIUS97/22104 -125- TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAM~E/KEY: misc feature LOCATION .510 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:21:

TTGTTTGAGA.

AAGGTAAGTA

AACAATGAAG

TTGAACAACA

TTAAACACCG

TTAAATGATG

TATTACCACC

GCTTACAATG

ATTTATTCTC

AATGGATTGG

TTAGTTTCAA

TGGTGTGCAG

AGCGAGAAAA

CTAAAAAGTT

TGGGTTTTGC

AAAAACACCC

GGGGAATGAA

AAGTGCGATA

TCTGACCTTA

GCAATACGAA

AACGCTCATC

ATCCCTTAAA.

CTACCCTACC

GATCCAATTA

CAACAAAAGC

ACACAACCCT

CAACGAATAA

CTCCTTAGTT

AATCTTATCC

TCTATCGCT'I

GACACTTCTT

TATTCTAAAA

GCCAAACAAA

GTGTATCAAT

AATGGCGCTT

CCTTAGGCTA

ATATCCATCA

TACTAGAAAG

ACTCCATGTT

CGCTCCTCAA

TTTTAAAAGA

TAGTACAAAT

ACATGAAGAA

TCCATGCCAA

AAAAGGTTGC

CTCTCTAGGG

CCATATCACC

AACCAAATTG

AAATTTTGAT

GGCCATAGGC

GTTTCGTTGC

120 180 240 300 360 420 480 510 INFORMATION FOR SEQ ID NO:22: SEQUENCE CHARACTERISTICS: LENGTH: 648 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAXME/KEY: misc feature LOCATION I1.. .648 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:22: ATGAAAAAAC CCTACAGAAA GATTTCTGAT TATGCGATCG TGGGTGGTTT GAGCGCGTTA GTGATGGTAA GCATTGTGGG GTGTAAGAGC AATGCCGATG ACAAACCAAA AGAGCAAAGC WO 98/24475 PTU9/20 PCT/US97/22104 126-

TCTTTAAGTC

TCTTACAAGG

CAAGGCAATG

GCCAAAATTG

GGATCAGGCT

AGTTATATTG

TACAAATCCC

GCTTCAAGCA

ACTAGTTCGC

AAAGCGTTCA

TTGTTGAAGA

AACGCGTGTT

ATAACGGCAC

TTGGCTTGGG

GCAATAAGCT

CACAAGCTTA

TGGGCACAGC

CTGCAATAAG

AAAAGGCGCG

ATACCCCAGC

GAGCAATGAA

GAGCAAGCTT

AAGCGCGATT

TTTTAATAAC

CCAACGCTCT

GAGTAAGGGA

CTCTGGGACA

TTTGTGATTT

TCAAGAACCC

GAGATTCAAA

GTCCAGCCTA

TTAGGGAGCG

CCTAATTATC

CAAAATTCTT

CAGAGCGGGT

AGGGGCTTTA

TAGAAGAGCA

ACATTGTAGT

AGCTCATCAA

ATAATGGAGG

CGGCGGGGGC

AGCAAAACGC

TTTCTAAAAG

TTTTTGGCTC

ACGCATAA

AAAGGATAAA

GCGCGATTTG

AGAAGAAGAA

GAGTAATGAA

GATTTTAGGG

CCAACGGACC

CGCACCCAGC

TAGTAGGCCT

180 240 300 360 420 480 540 600 648 INFORMATION FOR SEQ ID NO:23: SEQUENCE CHARACTERISTICS: LENGTH: 762 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION .762 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:23:

TTGAAAACTC

AAAGAAATCA

CCTAAALZCCCC

CAAATCTTAA

TATTCGCAAG

GGGTTTAACA

AGAATCTTTA

ATGGTGCAAA

TATCGCTTTA

ATTAAAACCG

CCTTTGCGTT

GAAATGCCCT

CCACGATTTA

TATTTAGTGT

CTTGGTCTCA

TAACCATTGA

AAAGGGCTTT

CCGCTTATTC

CCGCTACAGG

GCGTCTATAA

ATTACGGAGG

GGAGTTATTT

GCTCTTTCAC

TTGGTTTTAT

TAGTGAGGAA

ACGCTAA'-:"

TTATCTCTTT

ATTCTTGGAA

CAAAAACAAT

AGAAAAAAGC

AACCACTAAT

CTTGGAGCAT

CTATTTCCAT

CGCGTTAGAT

AGGAATCGCT

AACCATCATC

CGTGGATTTT

TGTTTTTTAC

TTCTTTAATC

TTGTCGTTGA ATCCACTCTT AATTTTAAAA ACAAGAATGA GAAAAACAGC AAATCCTAGA CTTAAATTTT TCTTTATTTT CAAAACTTGA CTCTTACGGC TTTTTAAGAA ACCACCCTAA TCCGTTTCGC TCTCCCAGCC TTTTCTTGGA TTTTTGTGGA TTAGAGCAAG GGGTGTTGTT CCAAGAACCA AGAAAACCTT ATCGGCTATT TGTCTTTGCA ACCTACAATA ACCATCAAGA GTTTCGTTTT AG

TTTAGAAGCT

AGACGACAAA

CAAAAACCAG

TGGATACAAC

GAATAGCATA

AGTCGGTTTT

TCAAATCCTA

TAAAAAAACC

AGTGGATACG

TTTTCAAGCC

ATTAGGGATT

AAGATTCAAA

INFORMATION FOR SEQ ID NO:24: SEQUENCE CHARACTERISTICS: LENGTH: 1011 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular WO 98/24475 PTU9/20 PCTfUS97/22104 -127- (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1011 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:24:

TTGTTTTTCA

ATTCCCACCC

GAAAATGATG

GGCTTTTCTA.

TTAGGGTTTT

ATGTATACCC

GGGGGGTATT

TTCACGATTT

ATTCATAAAT

TTTATCTTTG

TTTTCTATGG

CAACTCGGCT

GTCAATACCG

GCAGGGGCTT

ACTAGGGGCA

ATGTGGCGTA

CAGCCTAAGC

AATTTATTTT

CTTCAACCCC

GTTATATCAA

CTAAAGAGTT

TCAATAAAAG

CCTCACTTGC

TGAGGGTGAA

CTTTAGGCAC

GGGGTCATGA

AACTGCACTA

AGTTGATGCC

CGCTCTTTAG

CTTTTGATGG

TTGGGCGCTT

TTGCCAATTT

GCCTCAGGGT

ACCATCAGAT

ATGTTTATCA.

ATTAACGCCC

TCCTTACATT

TGATTTTTCT

CCCTAGGGTT

AAACAGAAAA

TTTGAAC!GTG

GACAGGGCAA

TCCCCAATTT

CCAATTGCTT

TGGGTTTAAT

GGCTGGGTAT

GGGCATGCCT

CCAACCCCTT

GGAATACTTT

GGCTTTTACA

CGGCACCTTA

TTAGGAATAT

TCTAAACGCT

GATGAGTATT

AAAAATAAAG

ACTCGTTTTG

CTGGTGCATT

TATAACCGCC

GATTCTTTGG

TATGGCTGGA

AAAAAAGTCC

GTGGAACTGG

AACTTGGACG

TATAGCGATA

AACATCTTCA

GTTTATGCCA

ATCACTGATA

GAATTGAATT

TTGCATGGGC

ATTCTATCAA

ACACGGCAGG

CGATGAAATG

GCATTTCTCT

TGCATGACAA

ATCAAACTTT

CCGCTCAAAC

ACACGCAGCT

CCCTTTTAA.A

GTAATGCGAG

CTGATTATGG

AGTTTTCCAT

TTCAAGGCAA

GTGAAATAGG

TTAGTAAAAC

TCGCCTTTTG

AAAAGAGGTC

TTTGATGACT

CAATCAAATA

GTCTTCGTAT

CGCCCAAGAC

CCACCCTTAT

CATGGAGTTA

GCAGCGTCTC

CAAAAACGAA

GACTCGTTTT

GGATTATTTC

GGTCAATAAG

CTATTTTTTT

TAGCCCTGAA

AGCGGCTATG

CTTTCAGTCC

120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1011 INFORMATION FOR SEQ ID SEQUENCE CHARACTERISTICS: LENGTH: 327 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc-feature LOCATION .327 WO 98/24475 WO 9824475PCTIUS97/22104 128 (xi) SEQUENCE DESCRIPTION: SEQ ID

ATGAAACCAA

CCCTTATTAG

TTTGTCATTA

AAACGCCATG

GCTGAAATCA

ATAGTGATCG

TCTTTAGCCT

AGCCGTTATA

AAAAAAAGCG

ATTTAGAAGA

ATGTGTCTTC

ATTCGGTCGC

CTTTTTCCTC CTTATTGTTT TTTCCCCAGT TACACGCAAT CGCTTACAGG CCTTTTCAAT GCGCCAGAGC AACCAACCAA TCAAACTTTT TTAAGAGGAA

TCAGTAA

TAAAAGCGCA

TTTTAGATTT

GGGGGAACAC

GCGATATTTT

TCAGCAGCGC

CCCCATAAAC

AGAACCTCAT

TATTATTATC

CCGCCAGAAC

TTCTTCACGC

120 180 240 300 327 INFORMATION FOR SEQ ID NO:26: Wi SEQUENCE CHARACTERISTICS: LENGTH: 588 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1 588 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:26:

ATGAGCAATA

TTGAACGGGC

GGGTTAAGGT

AATTCTTCTT

AACGATAGCA

CTAGCAGGGA

TACAGCGCGA

AATCTCGCTA

GGCATTAAA

TACAGAAGGC

ACCCCTTTAA

TTGGCGTGCA

ATTATGGTTT

CTGATATATG

TCACAAGAAA

CTACATGGCT

AAGTCAATGC

CAGCTAAGAA

TCCCTACCAT

TTTATAGCGT

AAAAGTGGGC

AGTGGGTTAT

CTTTGATTAC

GACTTATGGC

GAACAACAAG

TAATTCTCAA

TTCCAATTTC

AAAAGACAGC

TAACACCAAT

GTATCTCAAT

ATGATCAGCT

AAACAATTCT

AACCACGGCT

GGTGGGAGCG

CTTTCTGTGG

TACATGAATT

CAATTTTTGT

GAACGTTCCG

TATTATTCTT

TATGTGTTTG

CTCAAAACAA

TTGGCGAAAG

ATATCAAATC

ATTTGTTAGT

GTCTTTTTGG

TAACAGCGTT

TCAATCTCGG

CGCAACATGG

TTCTAGGCAC

CTTATTAA

TAACGGCGCT

CAAAAGATGG

CAGCTTTTTT

GAATTTTATC

TGGTATCCAA

CAATAACCCT

CTTGAGGACG

CGTTGAACTG

TAAGCTAGAA

INFORMATION FOR SEQ ID NO:27: SEQUENCE CHARACTERISTICS: LENGTH: 684 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) WO 98/24475 PTU9/20 PCTIUS97/22104 129- (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc-feature LOCATION 1 .684 (xi) SEQUENCE DESCRIPTION: SEQ ID, NO:27:

GTGCGTTTTG

TACCCCACC

CTCAATGAGA

TATCCATTCG

GTGTTGGTTG

TCTAAAGTGT

TATTCCAACC

TTGCCGTTTG

TCTTTAGCCT

TTGAAAACCA

TTAGGCAAAA

ATCCAAAAAC

GTAAAATTGA

CTTGTTATTT

GTTTTTTATT

CTCTTTGTTC

TAAATAGAGA

TAGGGTTAAA

CTAAAAAAGA

TTTTTGGGCG

TCAAACATCA

ACTTGAAACG

AGGAACAATC

CCAAGCGGTT

TTATTTGAAC

CAAACAATTC

CAGGCGCATT

TTATTCTCTA

AAACGCTTTT

AGGCGAGGTC

TTTTATAGAT

TCTGTGCTAT

AAAAACAAAA

CCAAGATATT

AGGCCTTAAA

TTAG

ATGCTCCCTT

TTACGGCTTA

GATGCGGGGT

GGCATTGTCG

GACAAAGAAA

TTAATCGGCA

TTAGCCGCTC

TATCAAAACA

ATCCCTCACT

CTAAACTACT

GCGTTCTATC

TTGATGTGTT

AAAAAACCTA

TTATTTCTTC

CTTATAAGGA

GCGCTTCTTC

ATAAAGCGCT

TGTGGTATGA

AGGATTTTTA

ACATCCTTAA

TGCAAAAAAT

GTGAATTGTT

TATCAAATCC

CCCCTCCAAA

TATCGCTGGC

AGTTTTAAGC

AAACGCCCTC

GCAATTTTAT

AAAAAAACGC

CAAACGCTTG

AGAAGCCGCT

TTACTACACT

GTTCAAACGC

INFORMATION FOR SEQ ID NO:28: SEQUENCE CHARACTERISTICS: LENGTH: 918 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 918 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:28:

ATGGGTAGAA

GTGTTGTGGG

TTGGGTTTTA

AAAGACAACC

TTGAATCAAA

GCAATGCGGC

GGCTAGGCAC

CCACTTGCCC

AAAGCGTTTG

TGAAAAAACG

AGGGGCTACT

TAGCAGCGTG

TTATACCGGG

AAAGCACTCA

CCTTTTTTTA

ACGCGCACAA

TGTTATGGCG

CAAATAGGCG

TTTTTTTAGC

AAACTAAAAA

GCATGTGGCA

AGAAATTAGA

ATGAAATAGC

GAGTTTGGGG

CCACATTTAT

ACAAGCCTAT

AGCCCATTAT

TTTTGATAAA

120 180 240 300 AAGGGGGGTA AAAACTTATC WO 98/24475 WO 9824475PCTIUS97/22104 130-

TACCATATTT

CAAAAAGTGG

ACCTACGATC

CAAGATTTCC

GTCAATCTCC

TTTAAAATAG

TATAAAAATC

GTGAATTTTG

ATCCCTTATT

CAGCAACAAA

TACGCGTTCT

TAGGCTTAAG

GGGGTAACAC

CTACTTCAAA

TTTTCAATAA

CTATAGACAC

GCGTGTTTGG

AAAATACCCA

GAGGCTCTTT

ATAGCTTGAG

CGATCCGACA

TGTTTTAG

GGTGTGGGGG

CCTTTTATCC

CGCTCAAGGC

CGGGCATTTC

CCTTTTAAAA

TGGGGGTGGG

TCAAGACGAT

GTATATAGGC

CGCGCAAAGT

AAACTTCAGC

GATGTAGAAT

CAAGCGAATT

TCTTTAGTTT

ATGGCGTTTG

CTCGCTTTAA

GTGGAATACG

AAATTTTTTG

AAGCGCAACC

TGGAAAAATT

GTTTTTAGGA

ACGCTAAGGC

ATAACCCAAG

TGCAAAAA-AC

GTTTGAACGT

AAACGGAAAA

CAATCTTGTG

CCGCAGGTGG

GCTTCAATGT

TTGGCTCTAG

ATAAAGAAGT

TCAATTAGGT

CGCGATTAAA

CCCAAGCCCC

GAACATGTTT

AATGCTGTTT

GAGTCCTCAA

GGGGTTTTTT

GGGGCTAAAA

CAATGTGTGG

TTTTGTCAGC

INFORMATION FOR SEQ ID NO:29: SEQUENCE CHARACTERISTICS: LENGTH: 777 base pairs TYPE: nucleic acid STR.ANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pyloni (ix) FEATURE: NAME/KEY: misc feature LOCATION .777 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:29: ATGTTTTTAA. GATCATACCC AAAGCTTAGA TACGCTTTAT GTTTACCCCT ACTCACTGAG

ACTTGCTATA

ACTTACAATA

GTCAAAGACC

CAGAAAATCT

GCGCAAAATG

AAAAGCGTGG

GGAGTGATTA

GCAGCGAGTG

GCCTATCAAA

TATAGGAGCG

CCAGGAACTC

AGAGACACGC

GCGAGGAGCG

ATGAGTTTAA

TGTTTAGGAC

ACGTGAGAGG

GCAACATCTA

AAGTTACTAA

AAATGGAGAC

GGGCGGTGAG

GCflCGCATTT .3C.3CCACAGT

CCAGCGAGCA

TCACTTTCAG

CACTTTAAAT

GGTTACTTCT

TAACCCTGAT

CATTGAAGAC

CCACCACCAA

AGGCGCGGCG

TAAAGGAGCG

TTTTTATACC

TGATATTATC

GATGAAAAAC

AAACAACGCT

CTGGAACATG

AAGGTTACCA

AAAGAATTGG

GTGAATGTGG

AGGCTTTTAA

GGCAACACCG

AATGCGAGCG

GCTGATTTTA

AATTTTGGGG

GCTTACTACA

CTTTTCAAAC

TTGATTAAAA

ACACGAGATA

CCCAAGCTAA

ATCAACGCCA

GCGGAGGGAG

GGGTTACGGT

TGATTGACCC

CGGGGCCAGG

TCCCTAGGGG

ACAGAGAGAC

CGCACCAAAA

CCACACAAGC

TGAATGGCTA

ACGCCACACG

AAGGATTTTC

AAGCAATGAA

CGTGATGGGG

GGATGGGGCT

TGGCATGCTC

AGCGATCGCG

GAAAAATTAT

TTTTAGATCG

TATTTTCTAT

CGATAAAGAG

TTTGAGCGAC

CCTTTAA

120 180 240 300 360 420 480 540 600 660 720 777 INFORMATION FOR SEQ ID SEQUENCE CHARACTERISTICS: LENGTH: 579 base pairs TYPE: nucleic acid WO 98/24475 PCT/US97/2104 131 STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: miscfeature LOCATION 1...579 (xi) SEQUENCE DESCRIPTION: SEQ ID

ATGTTTTTAA

ACTTGCTATA

ACTTACAATA

GTCAAAGACC

CAGAAAATCT

GCGCAAAATG

AAAAGCGTGG

GGAGTGATTA

GCAGCGAGTG

GCCTATCAAA

GATCATACCC

GCGAGGAGCG

ATGAGTTTAA

TGTTTAGGAC

ACGTGAGAGG

GCAACATTTA

AAGTTACTAA

AAATGGAGAC

GGGCGGTGAG

GCGCGCATTT

AAAGCTTAGA

CACTTTAAAT

GGTTACTTCT

TAACCCTGAT

CATTGAAGAC

CCACCACCAA

AGGCGCGGCG

TAAAGGAGCG

TTTTTATACC

TGATATTATC

TACGCTTTAT

AAGGTTACCA

AAAGAATTGG

GTGAATGTGG

AGGCTTTTAA

GGCAACACCG

AATGCGAGCG

GCTGATTTTA

AATTTTGGGG

GCTTACTAG

GTTTACCCCT

CCCAAGCTAA

ATCAACGCCA

GCGGAGGGAG

GGGTTACGGT

TGATTGACCC

CGGGGCCAGG

TCCCTAGGGG

ACAGAGAGAC

ACTCACTGAG

AAGGATTTTC

AAGCAATGAA

CGTGATGGGG

GGATGGGGCT

TGGCATGCTC

AGCGATCGCG

GAAAAATTAT

TTTTAGATCG

120 180 240 300 360 420 480 540 579 INFORMATION FOR SEQ ID NO:31: SEQUENCE CHARACTERISTICS: LENGTH: 381 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...381 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:31: GTGCCCTTGA GTTTGGGAGG CAACCTCTTA AACCCTAACA ACAGTAGCGT GCTGAATTTA AAAAACAGCC AGCTTGTTTT TAGCGATCAA GGGAGCTTGA ATATCGCTAA CATTGATTTA 120 WO 98/24475 WO 9824475PCTIUS97/22104 -132- CTAAGCGATC TGAATGGTAA TAAAAATCGT GTGTATAACA TCATTCAAGC GGACATGAAT GGTAATTGGT ATGAGCGTAT CAACTTCTTT GGCATGCGCA TTAATGATGG GATTTATGAC GCTAAAAACC AAACTTATAG TTTCACTAAC CCTCTCAATA ACGCCGTAAA ATTCACCGAG AGCTTTTTCA TACACCGCCT GTGCGGTTCG CTCTCTCAAA TACAAAAAAA AAAAAACACA.

ATAGTCTCAC CTCGGCTCTG A INFORMATION FOR SEQ ID NO:32: Wi SEQUENCE CHARACTERISTICS: LENGTH: 1698 base p airs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION .1698 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:32:

GTGTATTCTT

TATTACAACC

AATCTAACCT

AGCGCGTTAC

ATGGCGCTCA

AGTTTGAGCA

GATTGGAAAA

AATAACGGCA

GTGGTTTTTG

AAATTTAGAG

ATTGACACGA

GCATGGGGGA

AACCAAGCGA

GGCATCAATA

CAATCCATTA

AGCGTGATTG

GGGCAGAATA

TTGATCAGAC

GGCATTGATT

AGTAAAAAGG

GTCATAAGCG

GCCGCTTTGG

GAAAGCTTGC

GGATTAGGGT

GGGATTTTCG

ATAGCGATGA

CCAACCAATC

CTGAATCTTC

ACGTCTATAA

AACTCTACCC

ATTTAAAAGG

ACATTAACGA

CTTTGATTAT

GGGGCTTGGG

GCACTTATTT

CTTTTAACGC

CTGGGGGGAG

ATATCGTAAG

AGGTTTTCAA

ACAAAGCCGG

GGGGGTATTT

ATTTTGATAA

AAAAATTAGG

TGCAAAACCC

GGTTGTTCAA

TGATGCTGCA

GCAAGCAAAT

TGCAAAACCA

CTATTTATGA

CTCCCTATGG

CGCACAAGGC

CTATCAAGCC

TGTCATTTCG

CAAGGGCTAT

TGAAATCAAA

CGATGCGCTA

GTTGATTGAT

AGGAGCGACT

CTATCAAAAG

GGGGCAGCTT

TAAAGAAATT

TGCGAGCGTA

CTCGCAAACC

TCAAGCCGGG

GGGATTAGGG

AACGCCTGAG

CCTCATGAAC

CTTTTGGACC

TGAAAAGCTT

TCAGATCACC

AGATATTGTC

GATTGGCGAA

GCAGATTAAA

ACAAGGTTTG

CTTGAGTCAA

GTGTTTTATC

AGCGGCAGCA

CAAACCTATA

AATTTCAGTA

AAGATATTAG

AACCAGCTTA

AACGCAAACA

AAAATAGGGC

CCTTGCGATT

TTGGAGTCCA

TATCTTACCG

ACTTTTAACA

GATGGGATTT

CTCGCTAATA

AATTTGATAG

CAAAAAAATC

GATAGCGGTT

GGGCTAGTGG

ATAGGCAGCA

GGCTTTATTT

AAGCCGAGCG

TTTTTAGGCC

AGCGTTTTAG

GGGGATTTGA

GTGTGGCAAA

TCACGAGCAG

ATAACACCAC

ACGCGCAAGG

ATATCAAAGC

GGAATGATTT

CCAAGCTCAT

ATTCGGTCGT

AAACAGACAC

ACACTGATAT

ACTCCGCTGA

GCACTTTAGG

GCCAAACTTC

TTAGCATGCT

TTTTGGGCGA

TAAATACGCT

AAACCCTAAG

TGAACACG

GGGGATTAGC

TGTCCATCAA

CCGCTAACGA

ACGCTTTAAA

AAGACACGCT

ACAAAGTCTT

TCCCTAATCT

AAGGGGATTT

CGTGAAAGGC

GAAAAATAAC

CAACCCTATC

GTTAGGGCAA

TTCGCTTTCA

CACGCCTAGC

GCAAAATTTC

CAATAGTGCG

TGTGTGCCAA

TTTGGGCTAT

GAGCGGGAAC

GCTCATTCTC

GGGTCAAGAG

AGTGGCAATG

AGGGAGTGAT

CCAGCTTTTG

GATTAAGGAT

CGGACTGGGG

TGATTTATTG

TATAGGGCAA

AAACGATGTA

CAATTCTTTA

AGCGGCTAAA

TGGTAAAAAG

TAGTTTCAAC

120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1140 1200 1260 1320 1380 1440 1500 WO 98/24475 PCT/US97/22104 133- GCGCAAGGCA ATGTTTTTGT GCAAAATTQC ACTTTCTCTA ACGCTAATGG AGGCACGCTC AGTTTTAACG CAGGAAATTC GCTCATTTTT GCCGGAAACA ACCACATCGC TTTCACTAAC CATTCTGGAA CGCTCAATTT GTTGTCTAAT CAAGTTTCTA ACATTAACGT CACCATGCTT AACGCAGCAA CGGCCTAA 1560 1620 1680 1698 INFORMATION FOR SEQ ID NO:33: SEQUENCE CHARACTERISTICS: LENGTH: 519 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...519 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:33: GTGTTTGGAT TGAGTTTGGC TACCCTGAGC CTTACAAGTT AATCATAAAA TGAACGATTA GCCAGACAAG GCTTTGTCAG TTAAAAGATT TTTGTATTAA AAGCGCATTA ATGGCGAATT TATAGCGTTT TACCCGATAT GCGATTTTAT CGGTAAAAAA ATTAAAACTT TTGCAATCGC GGATATGATT TTAGAGCGTT TTTACAGGTT TTTTACGCGC TATCAAGCAA AATAAGAGCA CGTAATTGGA AGAGCGTTAG AAACAATGTA AAAATGACGA AGATAAGGTC AAACGGGCTT TATTCTTTAT CAAACCAACA TTCGTTTAGA GAGCGTTTCA CTGTAACTTC TCACATTAA TTAAAGATTT TATGAGAGAA AAGAAAAAGA ACGCTTCTTA AGGAAGAGGC TAGTATTTTG AAAAAATCAT AGAACTTTTA ACGATAAAAC CTTAAGGGCT TATTGGTGCA TTTTGGAGGA AAGATAATAT CAAAATCCTA CAAAAGACGC CTTATTGGAA 120 180 240 300 360 420 480 519 INFORMATION FOR SEQ ID NO:34: SEQUENCE CHARACTERISTICS: LENGTH: 996 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circulFr (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori WO 98/24475 PTU9/20 PCT[US97/22104 134 (ix) FEATURE: NAME/KEY: misc-feature LOCATION 1 996 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:34: ATGAAAAGAT TTGTTTTATT CTTGTTATTC GCTGAGCAAG ATTACTTTTT TAGGGATTTT

CTTGATAAAA

TACACTGCTA

ATGGTTTCCT

AAAGCTATAG

AGCGAGGACA

AAAGAATTTC

TCAGCTCTTA

GCGCTAGATG

AAAGCCATAG

TATCATGGCG

GCGATAACTA

GCCGGGCAAA

ACTTTCCCCT

TTAGCCAAAC

GAAGATGGCT

AGCTCTCCCA AACAATACAG

CTGGGGTTAG

ATGATTTAGC

AGATTTTAAA

ATATCAATTT

CTAGCCCAGA

ACACTAACCA

ATCATGCCCT

ATGAGAACGG

GCCCTACAAA

TATCAGGCGA

GGCTCTCTGT

ATTTTCAGCC

ATTATTCTAG

TCAGGCTGAA

AGAGCCTGAT

GCTAGGCTAT

CGCTTGGGCT

TTACATGCCT

ATATGAAGAT

TGGGGCGTGG

TTTGCAAAGT

GGTTATTGCT

GGGCATTAAG

ATTGCTTTTT

GGCGTATAAC

TAACCTCATT

CCCTAGCGCG

ACTCCGATCG

ATATGTGTTT

AAATCTATAG

CCATGCGCGC

GCCTGCACCA

TTAGTGAGCC

AATGAGCTTC

TATATGAACA

TTCATTAGGC

'GGGATTCTCT

AGCGCTAATC

AGCGCGATCA

GGGATAGCTT

GAGAACGGGT

AAA.GCCGCA.A

GGGGTGCATA

GATGAGCTTT

CCATGA

GCGTTTGCGT

ATTTGCCCCA

AACTTAACGC

AGAGTTTTAA

AAAACAAACC

AAAGCGTGGA

TGGCTTATTG

GGATGCGTCA

TTGATGTGAG

GGTGGCAGGA

CTAGGAGCGA

ATACCAATTT

ATGATTTGTG

CATGGATTCT

ACAACGCCTA

TAGAGCAAGG

TCAAGCTTAC

ATCAAAACAC

AAAATCCGCT

ATACGGCTTA

TACTTATCAA

GTTTGTCAAA

GTATTCTCAA

CTCTGCACTA

GTGGGTGTTT

TACGAGCGAT

TGCGCTTCTT

GGGTAGTGGA

AAACCCTGAA

TTTCATTATT

CGATTTGCAT

120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 996 INFORMATION FOR SEQ ID SEQUENCE CHARACTERISTICS: LENGTH: 384 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pyloni (ix) FEATURE: NAME/KEY: misc feature LOCATION .384 (xi) SEQUENCE DESCRIPTION: SEQ ID

ATGCGTCAGT

GATGTGAGCT

TGGCAGGAGT

AGGAGCGATA

ACCAATTTTG

GATTTGTGGG

ATTCTCAATC

CTGCACTAGC

GGGTGTTTAA

CGAGCGATTA

CGCTTCTTGC

GTAGTGGAGC

AGCTCTTAAC

GCTAGATGAT

AGCCATAGAT

TCATGGCGGC

GATAACTATA

CGGGCAAAGG

ACTAACCATG

CATGCCCTTT

GAGAACGGGG

CCTACAAAGG

TCAGGCGAAT

CTCTCTGTGG

GGGCGTGGGG

TGCAAAGTAG

TTATTGCTAG

GCATTAAGGG

TGCTTTTTGA

CGTATAACAA

GATTCTCTTT

CGCTAATCGG

CGCGATCACT

GATAGCTTAT

GAACGGGTAT

AGCCGCAACA

120 180 240 300 360 WO 98/24475 PCTIUS97/22104 -135- TGGATTCTAA ACCCTGAAAC TTTC INFORMATION FOR SEQ ID NO:36: SEQUENCE CHARACTERISTICS: LENGTH: 738 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...738 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:36: 384

TTGAGAACCT

ACAGAAGAAA

ACAGGTTCTA

ACCGGTTACA

TCTAATGGGA

GGTTTGCGCT

TATTATGGGG

TTCCAAGGGA

GCGATTGCTG

AATAGTAGTG

TTATTTGTAG

TACTACACCA

TATAATTACC

TGTTAAAAAT

GCGCTGCCCC

TCAATTTAAT

CCAATGTAAT

TTGGCTTAGT

ATTTTGCTTT

GCAATAACAT

GTTTTTATCA

GGAATAGCTG

CGGTTGATAA

ATGAACATGA

CCGACGCGCT

ACTTCTAA

GTTGGTTGGT

TTCTTGGACA

GACTAATATT

GACTAGCATT

CATGGGCTAT

TTTAGATTGG

GATCACTTAT

AGATGATATT

GTATATTGGC

GTGAGCTTAC

AAAAATTTGT

CATGAAGTTA

AATAGCGTTA

AACCACTTTT

CAAGGCTATG

GGCGTGGGCG

GGCGTGGATA

AATAAAGGGC

TAACACACGC

ATATGGGATT

GAGAAGTTAC

AAAAACTCAC

TCCATCCGGA

GCATGAGATA

TGGATGCGAT

TTGGCGTTTT

AGGAATTATT

TTAACTTTGG

TCCCCACTCT

.TCTTTGCCTT

TTTAATGGCT

CAATTACCAA

TAGCTATCAA

TAACATGGGT

TAAAGTCTTG

CCCTAAAGGC

ATGGAATTTC

TGGGGGGATT

AGGCATCACC

TTTCAAAGCT

TAACAACAAA

TTATGTGGGG

CACCTCTTTT .CAATTCCTCT ATTTGAAATT .GGGTTTAAAT CAAGGTTCAA ATGCGTAGGG INFORMATION FOR SEQ ID NO:37: SEQUENCE CHARACTERISTICS: LENGTH: 873 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: WO 98/24475 PTU9120 PCT/US97/22104 136- ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION .873 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:37: ATGTTTGAAG AAATTACCCT AAAATCGTTT TATCGGATGT

ATTCAAGTGG

CCCTTTTATT

TTAGAAAAAA

AATTTTGTAG

ATTGAAGAAC

CAGTTTTTAA.

GAAGTTTTAG

ATCAACGAAA

GGGGGGCTTA

GAAGAGAGCG

ATCATCAACC

GAAGATCTAG

ATAGACAAAT

CTGTGATTAG

TCTATCCTAT

ATTTAAGATT

GGGTGTTTGA

TAATCGCGCT

CCAATCATGC

AAGCCTCTAA

ATAAGGGCAT

TTAGGGTTAA

CGCTCATCCA

AACAATTGCT

GATTAGAGGG

ACGAAGCGGT

AGCGCATAAG

GAGTTTTAC!C

GGATTGTTTG

CGGTAAGAGG

CCACTCCCTG

TTTCACTTAC

CAAAGGGAAA

GAATTTTGTT

AGCGTGGTTT

TCAAAGCGTT

TGGGGAAATA

CATTGAAAAA

TTTGAATGAA.

CTTAAGAAGG

TGCTAGAAAT

GACTTGTTTT

AATTGCTTTT

GTGATTCAAA

CCGCATGAAT

ACTTTAGAGC

AACCGAGACA

AAATACCATA

TATGAAAAAA

TTAGAAAGCC

TTAGAAAATT

GTCTCGTTTA

GCCCGCACAG

TTTAGCCATT

TCTAAAA.TGA

TAA

CAAGGTTTTT

TATGGCAGCA

CCACTTATGA

GCGTGAAAGA

AAAAAGACGA

GGAGCGATTA

AGAAAAAAAA

TTTCTCCTCA

AGACCGATGA

ATGAAAGCTT

GTTTTGGGGA

ATATTGCAGG

TAACTTACGC

GCTATAACCC

ACAAACTCAA

CGCAAGGCTC

AAACCAAAAA

GCTTTTGGAA

TTTGAAAGAC

TGTTTATTCT

CCACTTAAAC

AAACAGAAAG

TATAGGGTTA

GGATTTAAAG

AGTTTTAAAC

CGCGTATCAA

TAACAGAGAA

GGTGTTTTTG

120 180 240 300 360 420 480 540 600 660 720 780 840 873 INFORMATION FOR SEQ ID NO:38: SEQUENCE CHARACTERISTICS: LENGTH: 333 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pyloni (ix) FEATURE: NAME/KEY: misc feature LOCATION I1.. .333 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:38:

ATGATGTTCA

CATTTCATTA

AAAAAACTCT

GGGGGCTATG

CAAGCGAATG

GGGCGTTTTT

TTGTAGCGGT

TCGCTAGGAT

GGTTTTTCAA.

TGAAATTAAA

ATAGCTACGC

TAATTTTCTT

TTTGATGCTG

TTGTGGGGTG

GCTTTTTGGC

GGGCATGGAT

CAAAAAAGCC

TTTGCGGTTT

GCGTTTTTGA

AAAGTGGAAG

ACGCAATTCG

AAAGAAGAAA

CTTTCCAAA.A

TAG

TCTTTGTCCA

TGTTTAGCAT

CTCTGTCTTT

ATGAAGAAAA

GCTATGGATA

TGAGTTAGGG

TGGTTTTGGT

GATCCCGCTT

TAAAATTAAT

TTGTTTGGTG

120 180 240 300 333 WO 98/24475 PTU9/20 PCTIUS97/22104 137- INFORMATION FOR SEQ ID NO:39: SEQUENCE CHARACTERISTICS: LENGTH: 1056 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION .1056 (xi) SEQUENCE DESCRIPTION: SEQ ID 140:39:

ATGATGTTCA

CATTTCATTA

AAAAALACTCT

GGGGGCTATG

CAAGCGAATG,

GGGGCGTTTT

GAAAAAGTCT

TTAAAGGGGG

AGAGAGATAG

ATTTTAGAAA

AATGAAATCA

GTCTCTTATT

GTTTTGATTG

AGTGGGGTAA

TTGTTTGGGG

TTAGATGGGG

ACGCCCATAC

TTAGGGCTTT

TTGTAGCGGT

TCGCTAGGAT

GGTTTTTCAA

TGAAATTAAA

ATAGCTACGC

TTAATTTTCT

TACTGCCCGT

ATAGAATCCT

TGGCGCGTTC

AACGACTGAC

TCAAGTATAA

CCGTGTTTCA

TGGATTCTTT

TAGGCATTGT

CGTTTTTATC

CGCAAATGCT

AAAATGCGTT

TTAATGACAT

TTTGATGCTG

TTGTGGGGTG

GCTTTTTGGC

GGGCATGGAT

GCAAAAAAGC

TTTTGCGGTT

CATTGGCGGT

TTCTATCAAC

TCAAGGCGAG

CCCCAAAATC

AATAATAGGC

AGCGTTTGAA

AAGGCGTTTG

GGGGGCGTTA

TATCAATCTA

AGGGGTCGTT

GTGGCTAGTG,

TACTCGTTTG

GCGTTTTTGA

AAAGTGGAAG

AC!GCAATTCG

AAAGAAGAAA

CCTTTCCAAA

TTAGTGTATT

TTAGAAAAAA

CATCAAAAAA

TTAATTTTAG

GTGGCGGTGA

ATTAAACCGG

AAGGCTTTGA

ATTATGGGGA

AGCCATGCCA

GGGATTTTAA

TTTAAAAATA

GGGGTGGGGT

CTATAA

TCTTTGTCCA

TGTTTAGCAT

CTCTGTCTTT

ATGAAGAAAA

AGCTATGGAT

TTTTTCTGGC

ACGCGCTAGA

TAGCGAGTTT

AAATAGAGCG

TAAGCGAGTC

ACATGCAAAA

GTCGGTTTAA

GCGCTTCAGT

ATAGCGTGAG

ATTTATTACC

TTTTTCATAT

TTTTGGTTTT

TGAGTTAGGG

TGGTTTTGGT

GATCCCGCTT

TAAAATTAAT

ATTGTTTGGT

ATTGAGCGGG

AGCCGGGCTG,

TAGAGAGATT

AAACAATCAG

TAATGATCCT

AATGGGCGTT

AGAGGGCGTT

TAAAGAATTG

CATGCTTTTG

CATTCCAGCC

CGCTTTGCCA

TGTCATGTTT

120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 1056 INFORMATION FOR SEQ ID i)SEQUENCE CHAR.ACTERISTICS: LENGTH. '03 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genornic) (iii) HYPOTHETICAL: NO WO 98/24475 PTU9/20 PCT/US97/22104 138- (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc-feature LOCATION .303 (xi) SEQUENCE DESCRIPTION: SEQ ID ATGCAAAAGA ATTTGGATAG AATGAATTGA GCGATCTTTT

AAACAAGAAA

AAACGACTCA

GCAGAGGTTT

TAA

GCCCCCAAGA

GCCAAAGGGG

TTAAGATTTC

TCTTTTAGAA

AGACAAACGC

AAACCCCATT

TTTCAAGCAT

TAGAAATTTT

AATTTAAGGG

TTAGGAATCG

TATTGCCCTA

TTGAATGGAG

CAAGAAAACG

CTGAAATTGA

CTTTAAAAAT

AAAGAGAGCA

AAATCCTTGC

CCCTAAAAGA

TGCGTTGGAT

CGCTCTCATC

AGAGATTTTA

AAGTTTTTAT

GTTAAAAAAA

INFORMATION FOR SEQ ID NO:41: SEQUENCE CHARACTERISTICS: LENGTH: 525 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION .525 (xi) SEQUENCE DESCRIPTION: SEQ ID N0:41:

GTGAAAATGC

TGGCTTTTAA

GAATACGCCT

CCTTGCATGC

AAAGATCCGC

GAGCGTTTTA

AGTGATTCTA

TTAAAAGATA

GTGTGGCAGT

GTTTTTTTAG

AAGGGGCTTA

ATAATGAAGT

TAGCGCATAA

AAAGCTACAT

AAAAAGAGGG

TAATTAGATT

GAATCACTGA

TTAAGGATTG

TGGTTTTGGG

TGATGTGTCA

CTTGCAACAA

GAGTTTGGCG

GGATAACTTT

TTCTTTAGAA

TTTATTGGAA

CATTCAAGCC

TAACCATTTG

TTTGTTAATG

GGCTTTTCTA

CGGCGCATCC

TTCAAACGCT

TATAAGGAAG

GAATTGGAAT

AAGGGCGTGA

CTTTTAGAAT

TTGCAAAAAT

AAAGCGTTTT

TGGGGGCGAT

ATTCCTTATT

TGCAACTTTT

TGGGATTGGA

TTTTATTGGA

AGATTGAAGT

TTTTTATGCC

CTTAA

GTTTGAAGAG

TAAGGCGATA

GTTGTTTTCG

CTTGTTTCA.A

CGCTCAATTG

TTACAAGTAT

GTTTATCGGT

CTTAGTTCAA

120 180 240 300 360 420 480 525 INFORMATION FOR SEQ ID NO:42: SEQUENCE CHARACTERISTICS: WO 98/24475 PTU9/20 PCT/US97/22104 -139- LENGTH: 1416 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION .1416 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:42:

ATGAAAAATA

TACCACACGC

GTGGCGTTAG

CAACAAAACA.

CAAGTGGGCG

ATGGACGCTC

AACAACGCAG

ACGAATAAAA

AACTTGGTTA

ATTATAAAAG

GCGCTTTTAA.

CTATTAGCCC

GAAAACTTGA

GATCGAATCG

GATGAGCCAT

GGCTTTGGCA

CGATATTACG

AAAGCGAACA

GTTTTTAGCG

ACTTGGGATA

ACGAATTTCC

CGCCGGTTTT

CCAGCTATCA

TATGCGTTCT

CCA.ATACAAA

TCAAAAAAGG

CTGAAGACGA

TCAACAACAA

TGGGTATGGC

TTTTAGGGAT

AGTTAACCCA

ACGCTTATAG

ATAATAGTAA

TTCTCTATGG

ACGCGCTCAC

AAATGCAGCT

AGAACGGTGG

CTACTTACCA

ACCTACCCCA

TTCAAGTGGG

CTTTCTTTGA

TCTTTACTTA

ATCAGTCCTT

GCTCTTTAAG

AATTTTTGTT

TGAGCGCGTC

ATCAAAGGTA

ATATCAATTA

AGAGATAAAG

GCTTTTA.AAA

TGGCTTTTAT

AGGCAGCACC

AGGGGGTAAT

AGGCAACCAA

GTTTAAAAAA

CGTTCAAGCC

TAATGGTAGC

TTCTCAAAAT

GAGAGTGAAT

TTTTAATGAC

TGCAGGGGCC

AGAGAATCTA

ATTTGGGCCA

CTATAAGCAA

TTATGGCTTT

TGGTGCTGGC

GAATGTGGGG

AGGTCAAATT

TAATTTGGGC

TCAAAGCATT

TTTGAAAGCG

CACGATAGGT

AATACAAGGA TGAAAAAAGG ACCGCTCTGC TTTTTAGCCT ATGGGAGTGG GCTATCAAAT CTAAGGAATA ATGTCATTGA

GGGCTTTTAG

ATTGTCAATA

ATACTCCCCC

TTGCAAGTGT

AATAATGGAG

GAATTCAGTC

CTGGATAGTA

ACTTCTTCAG

ATGCTTCAA.A

AAACAGCTAG

GGCACAAGCT

TTTTTTGGGA

ACGCAATTGG

ACGGACTTTT

GTGTTTGGGG

GAAAACTCGT

TTAAGGGCTC

CAGCATGGTA

AATGGGGCTG

TTTTAA

CTTTAGCGAC

CTAATACAAC

AAATTGAACA

ATTTGAGTAA

TCGTTCCTGA

TCTTAGCCAC

ATTCGGTGTT

CAAAGCTAGG

AGGATGTGAA

GAGGGATGTT

CTCAGCATGG

GCAAGAAGAA

GCAGTCTTAA

TATGGAATAT

GCATTCAAAT

TTAAAGAATA

ATTTTGCCAG

TGGAATTTGG

ATGTGGATTA.

TTATAGTCAA

TCCTTTAAGC

CGGCGGCGCG

TGATTTCCGC

AAACACGACC

TGTTGGCAAC

ACGCTTTGAG

TGTGCTTTAT

ATATGTAGGG

GGAGAGTGTG

TTTAAAAGGG

TCAGATCGCA

AACCATCTCG

AAAGAATTAC

GGTTATTAAT

TATAGGCTTA

CAGTGCTGTT

CTTTAGAAGG

AGCGGGTAAC

CACCATGCAC

CGTGAAAATC

CAGGCGTTTG

120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1140 1200 1260 1320 1380 1416 INFORMATION FOR SEQ ID NO:43: SEQUENCE CHARACTERISTICS: LENGTH: 390 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genotnic) WO 98/24475 PCTIUJS97/22104 -140- (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...390 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:43:

ATGAAAAGCA

GTCTTACTAG

AGTCTCCCTA

ATCTCTGTGG

TTGAGCGCTG

AGCTCTCGTT

AATTTCTCCA

TCAGAAGAGG

CGATTGTGTT

ACGCTAAAAA

ATGAGCATGA

TAGTCAAGCA

TTGAAACTTT

TCTCCACGCA

CGATGGGCTG

GAGTATTTCT

TGCGGAAAAA

CAATATTTTC

AACAGACCCT

TATCAGCATT

AGCTCAGTAA

AATGTTGTCC

ACTTTTATCG

TCCCAGCCAA

GTAGATGACA

AAAACCCTTA

ATGGATATTT

CTTTCATTGA

CGCAAGGTAA

ACGATCAAAA

AACCGACGAA

TAGATTTAAA

TAAAAGAGCA

TATTATGCTC

GATTAAAGTC

AGTGGTGGTC

TTTAGAAGCT

AAGCGACAAG

TAATCATGAA

INFORMATION FOR SEQ ID NO:44: SEQUENCE CHARACTERISTICS: LENGTH: 225 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: miscfeature LOCATION 1...225 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:44: ATGCTCGTCT TACTAGCGAT TGTGTTGAGT ATTTr .CTT TTATCGCGCA AGGTAAGATT AAAGTCAGTC TCCCTAACGC TAAAAATGCG GAAAAATCCC GACCAAACGA TCAAAAAGTG GTGGTCATCT CTGTGGATGA GCATGACAAT ATTTTCGTAG ATGACAAACC GACGAATTTA GAAGCTTTGA GCGCTGTAGT CAAGCAAACA GACCCTAAAA CCCTT INFORMATION FOR SEQ ID SEQUENCE CHARACTERISTICS: LENGTH: 672 base pairs WO 98/24475 WO 9824475PCT/US97/22104 141 TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1....672 (xi) SEQUENCE DESCRIPTION: SEQ ID

ATGTTTTCAC

TTTTTAAGCG

GGCACTCAAA

GCTGGTTTAG

CTTTTAGTTT

AATGTCAAAG

AGCTATTCTA

ATCAAAATGT

GTTTTATCCG

CAATTTTTAG

TTTCTTATGT

CTTGCAAATC

GCTCCAAAGA

AAGATGTTTT

TTGGCCGTAA

AATTGCGCAA.

AAGAGCATAA

CCACAGAAGA

ATAAAACCGG

CCGTGTTAGA

TTCCAAGAAA

CAACAATAAA

ATTAAACGAC

TTTAGACAAC

TGGTTGCTCC

CTATATTAAA

TTTTAAAGTC

ATTAGCGCAA

CAAAACCATC

ATTTATCGGC

TTTTTAAGCG

GACAAATTGG

AAGCGAGACA

AAGTCCATTA

TATTGTGAAA

GAGCATTTTA

GGCGATAAGG

ATTTATGC!CG

TATGAATTGC

GATGGGAAGT

ATCAAGTATA

TGTTGCTATT GATTTCGCTG

ATGAAAATCT

ATATAGACAA

GCCCTAATGA

GGCTTAAAAA

GTGCTTACTA

ATAAAAATGA

TCCAATCCAC

CGGGCTATAT

ATCAAGACAC

AAACCAACCT

TTTAAGCTCC

AAAGAGCTAC

TAAATACATG

AGATCTCAAA

TGTCAATATC

TGAAAAAGAA

CCCTACGATT

GCCTTCTGTG

GAAAAACGAT

TTCTAAGAGC

120 180 240 300 360 420 480 540 600 660 672 GAGGATCTCA CTAAAAAATT AAAGGCTTAC AAGTCCAGCT AG INFORMvATION FOR SEQ ID NO:46: Ci) SEQUENCE CHARACTERISTICS: LENGTH: 351 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc-feature LOCATION .351 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:46: WO 98/24475 WO 9824475PCT/US97/22104 -142-

TTGATGAAAT

GCCTGCAAAG,

CAAAACAATC

GATGAAAAAG

CTAAAATCAC

ATGAGCCTA.

AAATCAATCA

TCACCAAAGA

TCATTTTATC

AAAATCGTCC

ACCTAATAAG

AGTGAATGAT

GTTATCTCTT

CAATCGCACC

GATATAAAAA

CTGATCAATA

CAAAAAAGAA

CCACTCAACA

TTGTTTTAAG

AAAACAACAC

AGATTGAGCA

ACGAAAATAA

CGAACAATGT

GGAAGTATTA

CGTGTTGAGC

TAAAACCACT

TGAAGAAGAA

AATTGATGAA

TTTGCAACG.A

A

120 180 240 300 351 ATCAATAATG AAGAAAACGC TGATCCTTCG GCCACTAACC ACCAAGACAA TCTCAGTTCC INFORMATION FOR SEQ ID NO:47: SEQUENCE CHARACTERISTICS: LENGTH: 240 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genornic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION .240 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:47: ATGTTTGAAA. AAATACGCAA GATTTTAGCG GATATTGAAG ATGCTTTTAA AATTAGCGAA TTTGAGTTTG GGGGATTTTA ATGGACATGC CAAAGGGCGT GAATGAAGCG TTTTTTAC!GC CGCCTAAAGG AGCTTATCAA CGCTTTGAAT AAAATCAAAA INFORMATION FOR SEQ ID NO:48: Wi SEQUENCE CHARACTERISTICS: LENGTH: 156 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori

ATTCGCAAAA

TTGAGATTAA

AATTAAGCGA

AAGGGTTATT

TGAAATTGAA

AAGAGGGAGC

AGAAGTGGAG

GGTGTTTTAA

120 180 240 (ix) FEATURE: WO 98/24475 PTU9/20 PCTIUS97/22104 143- NAME/KEY: misc-feature LOCATION .156 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:48:

ATGTCTATGT

GCAAAAATTG

TTCGCACTAG

TCATTTCTAA TCTGGCTTTC ACGAGCGAAC ATAAGGACGC TATGGAAGTG CGATTTTACT CGGATCTTTG ATTTCTGGGA TCATAGGGGC TTTATATTTA ATAAAAGAGC GGCTTTAAAG AAATAG INFORMATION FOR SEQ ID NO:49: SEQUENCE CHARACTERISTICS: LENGTH: 1350 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1. .1350 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:49:

ATGGGTTTGA

CTCAGTTTGA

TTGAACGCCG

CTATGGCACA

AACTGGATTG

CGAGAATTGT

GCCATAGGGG

TCTCAGCATG

ATGCTTTTAG

GCTGATGACT

GCATGGCTTT

ATCCGATCGC

AGCGGTATCC

CCTAAAGATT

TCAGGAGTGC

AGTGCTTTAC

TTCATCATGC

TTAGAAGTGG

GGGATTTTCT

ATCGGCTGGT

ATGTTCATTT

ATTGCGATTT

AAATAAAAAT

CGCTTAAAAA

TTTTAGCGAT

CCCCTTTTGG

ATGATGTCTT

TGTTTGGGGA

GCATGATAGC

GTTTTGGGAT

GCAAGAGGGT

TAGGGGCTAT

TAGGGGCTTT

TCATCCCTTA

ATGCGACGAT

CTAAAAATGT

TTTTAACCAA

AAAGCCCCTT

CCTTATTCGC

ATAAGGTGCT

TAATCACTTT

GGCATATTTT

CTAATCTGGC

TACTCGGATC

TTTAAGGTTG

CTTCATTAAA

GGTGGTGGCT

GTTTCAAGTA

AATGGCGTTA

ATTATCCAGT

TCCAGGATTG

CCCTATGGCA

GCCAACCGCC

TGTGGTGATC

AGGGGTGGTT

CTTGCTTTTA

CGCTGCGGTG

AGAGCTTTTG

AGAGCAGCAA

AGAAAGATTG

GTTTGCAAAC

TTTAGGGGTT

CATAAGCGAA

AGGGGCTGGG

TTTCACGAGC

TTTGATTTCT

TCTATGAATC

AGCGAGTCTT

AATTCGTTTT

GGGGATTTTT

TTCTTTTTAA

TTTAAAAAAG

ATTTATTTTT

ACGGATATTG

TTAAAGGTTT

GCGCTCTTTT

CTTGTTTTAG

GGGGTGTTGC

GTTCTAGCTT

GAATTAGGCA

GAAATCTTGC

GAGCATTTTC

GCTGGGGTGA

ATTTTAGGGC

AAGCTTAAAA

CTTTTAGCAG

GAACATAAGG

GGGATCATAG

TCAAAAAAAC

TTGGAGGGAT

TAAAAGAAAG

TTATCGGCTT

TGATAGGCTT

CTTCTTTCCC

TTCTTAACGC

CGTTCGCTTT

TTTTAATCAC

ATACCACGAA

CCATATTGAA

TTTGGTTTTG

TTATGATACC

AACGATACGC

ATTCTATTGA

TAGCCCCCAT

GCGTTGATTC

TTTGTTTGGG

TCACTGCGCG

GGATTGGCTT

ACGCTATGGA

GGGCTTTATA

AGAAAACGCG

TTTCCTCTTT

TTATTTTGCG

TAGTTTGCAC

AGAGATCAAG

TGTGATCGCA

CAACACGCCC

AGGCGTGATC

TCTAGCGGTG

TTTAAAATTC

CCGCCTGAAiT

CGTGCATCAA

GG"1GAAAATC AC AGACGAGT

AGAAAAAGCG

CAGCGGGTAT

TAGCATCAAT

CAAGCCTTTA

CCCTAAAGGC

TACCATGTCT

AGTGGCAAAA

TTTATTCGCA

120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1140 1200 1260 1320 WO 98124475 PTU9120 PCTIUS97/22104 -144- CTAGATAAAA GAGCGGCTTT AAAGAAATAG 1350 INFORMATION FOR SEQ ID SEQUENCE CHARACTERISTICS: LENGTH: 2448 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION .2448 (xi) SEQUENCE DESCRIPTION: SEQ ID

ATGAATGACA

ACGTTTGAAT

GATAAAGAAA

TTTAATTACA

CAAATCAGCG

GCGCAAAAAA

GTGGCGCAAA

CTCAAAAGCG

ATTGGCGCGA

TACGCCATAA

GCG~CTTATC

TATTATCGTG

GTTACAGCAA

GAAAGGGATA

AGAGCGAATT

AACGAGAAAA

AGCGTCAATT

GGCGATCCTA

CTTTTCAGAC

CAAGGCGAAG

TGCTCCATCA

ATCATCAATT

CTTTTGGAAT

AGCGAATTAG

GATCCTAACA

TATGCGCAAG

GACGTTTATA

AGCGCGGCTT

GTAACTAGAG

AGCGTTTTAG

TAGAGGCTAA

AGAACGCCCA

ACAACCAGAC

ACATGTTTAG

TTTACGTGCG

TGGGCGCAAG

TGGTGGTTAC

TCAAAATGGA

GTGGGGCTGC

(GTAACCAITCA

ATGGGGATAA

GCCCTAGCGA

CCTTAACGCT

TTACCGGCAC

ACCCTAGCGA

TAGTGCATAA

AATTAAAAAT

CTAGCGATAT

AAAATCAATG

CTTTTAAAAG

CTGGGTTTAA

ACGGGTTGAA

TCAAGCCCGG

TGAACGGGCG

CGAATTACAC

CTTTAGTGGA

TAAACGTCTC

GCCCTATGCC

AAAATATTGT

AGAAGAAGAA

ACACACTTTG

AACCATTTCA

AAGAAACCCC

CGGTATTGAA

CTATGGGCAT

CAAGGGGGCG

GACTAGGAGC

CACTTTTTTA

TTTTGATGC

CGCGATGAAA

ACAAAACAAT

CAGTTATAAC

TTTTTTACCC

TTGTTTGTTT

CGTGAGCTTG

CAATGGCTAC

AGCGACTACC

CGTGGCGCAA

CCTTGGAGC

TGCGAACGTG

TTACCAGAAT

CGATGCCCCT

CTGCCAACGG

CTTGCACCCT

TAAAGACTGG

GCCTTTAGAA

TGGAGGTTTG

AGTTTTTCTA

AAAGAAGAAA

GGTAAAGTTA

AGTAAAGAAT

AATATCAATG

GACAGATTGG

CAAGGCAATA

GCTCAAGCGA

GCGAGCGATT

ACCAACTTTG

_CTTTTGTATT

AATCTTTTTG

GTGATGGCTA

ATGACTAGAG

TATTCTTGTG

GAAAATGACG

AATTATGAAA

ACGAGCATTA

ATTCCTTTCA

GGGGGCATTT

GGTTCTGTTG

ATCCACACCA

TTAACCACTT

GATGCGTGCT

AATGGCGCTA

ATGGTAACTT

CAATTGCACG

AATTTGAATT

GTGTGGATGC

TTTTTTTGTC

AAAAGACAGA

CCACTCAAGC

TAGAAAGAAG

TGGGCGGTGG

CTAGGGTTAC

CAATCATTGA

GCGCGGGGCC

TTATCCCTAA

GGGATAGGGA

ACCCTAAAGC

AGATCAATGG

ATAACGCCAA

GTGATTTCAA

CCAGTTTGTT

GGGAAGGGGG

GGAATGTCCA

CCCCAAACCC

ATGACGCTCT

TCGCTAATAA

TAGACCACAA

TTGATAAAGC

TAAGAGTTAC

CGGCGAATGT

TAGGGGCAGG

TAACTCAAGG

TCAGGCTTTC

GTCAAGACAA

CTTATTAGGA

AAGGAACAAA

GGCTAAAATC

GCAAGCCAAC

TGCGGTGATA

GGTGGATGGC

CCCTGGAATG

TATGGCTTTA

AGGCAAAGAC

AACCATTATG

AAATATTTTT

GGATAATAAA

TTATTTGAGC

TCGCCCTTTA

CGCTTTCCCT

TAAAACTTAT

GAGTCGCTTT

AATTGATCCG

GCAGCTCTCT

TAAACAAACT

AAATTTATTC

GAATGACAAT

GATCCCTGAT

AGGACCTGAT

GGTTGGGGTG

GACTCGTTAT

GTTTAGCCCT

TTACGCGTAT

TTTGCGCTAT

120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1140 1200 1260 1320 1380 1440 1500 1560 1620 1680 1740 WO 98/24475 WO 9824475PCT/US97/22 104 145

AACCGCAATT

CAGTATTTTG

TTTTCTTCAA

TATGAAGTTT

TCATGGCCTT

GGCAATGTGT

TGGCTTTCAC

CCTACGGATA

CATAAACCCG

CTCAAAGGGT

CAAGCAAGCC

GCAGjAGCCTG

TAAAGCCAGA

ATTTCAGAGC

CGCTTTTTGT

CAGGGACGGC

CTTTAAAAGG

TTATTTTAAC

GCTTTGTTAC

TTGACAGAAG

GCTATGGGGT

TGAGCCTGAA

CGGTGATGAG

GCTTTAACGC

AATTGGGCAA

CGCCGGTTTT

CACCAACTTG

TAAATACAAG

GCGTTTGATC

GGCAAGCTAT

TAATTTGAGT

GCCTAGTAAT

GAGCAGTTTC

CGCGGTGTTT

CCCTGATGAA

TAGGTTTGAA

AATGCGGAAT

GTCCAATTGA

CCCGCACAAG

GGTTTTTCTT

GCTGACGTGT

ACAATCCCAC

TATTGCTCTT

TGCCCTAAAA

TTTATCACTT

AATAATGTTT

CCCAATCAAG

ATTTCTTATA

TTAACACCGA

TTTCTAATTA

ATATTATTTA

TAGGCTTGAG

ATGAATTGGC

GCACCGGCCT

ATAGCCCTTA

CGCCCGGGAT

ACAAGCCTAC

TTAACCAACA

ACAAATACGC

AGTTTTAA

ATACAGCAGT

CATCAATCAA

TGTGCCTGGC

CGTGGCGCGA

GGCTACGACA

TAGCATCACT

TCGTAACGGC

TTTTCATGTG

TTATAAGAAA

ATATATTGAT

AAGGGGCATG

1800 1860 1920 1980 2040 2100 2160 2220 2280 2340 2400 2448 INFORMATION FOR SEQ ID NO:51: Wi SEQUENCE CHARACTERISTICS: LENGTH: 2445 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION .2445 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:51:

ATGACAAGCG

TTTGAATTAG

AAAGAAAAGA

AATTACAACA

ATCAGCGACA

CAAAAAATTT

GCGCAAATGG

AAAAGCGTGG

GGCGCGATCA

GCCAT rG

GCTTATCGTA

TATCGTGATG

ACAGCAAGCC

AGGGATACCT

GCGAATTTTA

GAGAAAAACC

GTCAATTTAG

GATCCTAAAT

TTTTAGAAAA

AGGCTAAAGA

ACGCCCAACA

ACCAGACAAC

TGTTTAGAAG

ACGTGCGCGG

GCGCAAGCTA

TGGTTACCAA

AAATGGAGAC

GGGCTGCCAC

ACCATCATTT

GGGATAACGC

CTAGCGAACA

TAACGCTCAG

CCGGCACTTT

CTAGCGATTG

TGCATAACGT

TAAAAATCAA

ATATTGTAGT

AGAAGAAAAA

CACTTTGGGT

CATTTCAAGT

AAACCCCAAT

TATTGAAGAC

TGGGCATCAA

GGGGGCGGCT

TAGGAGCGCG

TTTTTTAACC

TGATGCGCTT

GATGAAAAAT

AAACAATGTG

TTATAACATG

TTTACCCTAT

TTTGTTTGAA

GAGCTTGAAT

TGGCTACACG

TTTTCTATTT

GAAGAAA.AAA

AAAG.TTACCA

AAAGAATTAG

ATCAATGTGG

AGATTGGCTA

GGCAATACAA

CAAGCGAGCG

AGCGATTTTA

AACTTTGGGG

TTGTATTACA

CTTTTTGACC

ATGGCTAAGA

ACTAGAGATA

TCTTGTGGTG

AATGACGCCA

TATGAAAGGG

AGCATTAGGA

TTTTGTCCTT

AGACAGAAAG

CTCAAGCGGC

AAAGAAGGCA

GCGGTGGTGC

GGGTTACGGT

TCATTGACCC

CGGGGCCTAT

TCCCTAAAGG

ATAGGGAAAC

CGCACCAAAA

CTAAAGCGGA

TCAATGGTTA

ACGCCAATCG

ATTTCAACGC

GTTTGTTTAA

AAGGGGGGAG

ATGTCCAAAT

ATTAGGAACG

GAACAAAGAT

TAAAATCTTT

AGCCAACCAA

GGTGATAGCG

GGATGGCGTG

TGGAATGCTC

GGCTTTAATT

CAAAGACTAC

CATTATGGGC

TATTTTTTAT

TAATAAAGTT

TTTGAGCGAA

CCCTTTAAGA.

TTTCCCTAAC

AACTTATAGC

TCGCTTTGGC

TGATCCGCTT

120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 1080 WO 98/24475PTUS7214 PCTIUS97/22104 -146-

TTCAGACCTA

GGCGAAGAAA

TCCATCACTT

ATCAATTCTG

TTGGAATACG

GAATTAGTCA

CCTAACATGA

GCGCAAGCGA

GTTTATACTT

GCGGCTTTAA

ACTAGAGGCC

CGCAATTTAA

TATTTTGATT

TCTTCAACGC

GAAGTTTCAG

TGGCCTTCTT

AATGTGTTTA

CTTTCACGCT

ACGGATATTG

AAACCCGGCT

AAAGGGTTGA

GCAAGCCCGG

GAGCCTGGCT

GCGATATAGC

ATCAATGCGT

TTAAAAGCCT

GGTTTAATGC

GGTTGAATTA

AGCCCGGCGA

ACGGGCGCTG

ATTACACCTT

TAGTGGATAA

ACGTCTCGCC

CTATGCCTGG

AGCCAGAAAT

TCAGAGCCGC

TTTTTGTCAC!

GGACGGCTAA

TAAAAGGGCG

TTTTAACGGC

TTGTTACTAA

ACAGAAGGCC

ATGGGGTGAG

GCCTGAACGC

GACTACCATT

GGCGCAAGGG

TGGAGGGGGT

GAACGTGATC

CCAGAATTTA

TGCCCCTGAT

CCAACGGAAT

GCACCCTATG

AGACTGGCAA

TTTAGAAAAT

AGGTTTGGTG

TGGGCA.AAAT

CGGTTTTGTC.

CAACTTGCCC

ATACAAGGGT_

TTTGATCGCT

AAGCTATACA

TTTGAGTTAT

TAGTAATTGC

CAGTTTCTTT

GGTGTTTAAT

CCTTTCACCC

GGCATTTATG

TCTGTTGTCG

CACACCATAG

ACCACTTTTG

GCGTGCTTAA

GGCGCTACGG

GTAACTTTAG

TTGCACGTAA

TTGAATTTCA

TGGATGCGTC

GCGGAATTTA

CAATTGATTT

GCACAAGATA

TTTTCTTTAG

GACGTGTATG

ATCCCACGCA

TGCTCTTATA

CCTAAAAC!GC

ATCACTTACA

AATGTTTTTA

CAAACCCGCA

ACGCTCTTAA

CTAATAAAAA

ACCACAAGAA

ATAAAGCGAT

GAGTTACAGG

CGAATGTGGT

GGGCAGGGAC

CTCAAGGGTT

GGCTTTCTTA

AAGACAATTT

ACACCGAATA

CTAATTACAT

TTATTTATGT

GCTTGAGCGT

AATTGGCGGC

CCGGCCTTAG

GCCCTTATCG

CCGGGATTTT

AGCCTACTTA

ACCAACAATA

AATACGCAAG

TTTAA

GCTCTCTCAA

ACAAACTTGC

TTTATTCATC

TGACAATCTT

CCCTGATAGC

ACCTGATGAT

TGGGGTGTAT

TCGTTATGAC

TAGCCCTAGC

CGCGTATGTA

GCGCTATAAC

CAGCAGTCAG

CAATCAATTT

GCCTGGCTAT

GGCGCGATCA

TACGACAGGC

CATCACTTGG

TAACGGCCCT

TCATGTGCAT

TAAGAAACTC

TATTGATCAA

GGGCATGGCA

1140 1200 1260 1320 1380 1440 1500 1560 1620 1680 1740 1800 1860 1920 1980 2040 2100 2160 2220 2280 2340 2400 2445 TGATGAGCCC TGATGAACCC AATCAAGACA TTAACGCTAG GTTTGAAATT TCTTATAAGT INFORMATION FOR SEQ ID NO:52: SEQUENCE CHARACTERISTICS: LENGTH: 1584 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION .1584 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:.52:

ATGAAACAAA

AAAGTAAGAT

GCTGAAGAAG

GTGAAAAACC

ACAAACAACA

AACCTTTTTA

AATCTTCACC

ATTTAAAGCC

TCTTAGCCCC

ATGGGGGCTT

CGGGTAAAAT

CCAATATCAA

TGAACCAATT

AATGCGGTAG

ATTCAAAATG

TTTGAGCCTA

TATGACCTTT

CAAAGCCGAA

TATTGCAGGC

GGGCAATTTG

CACTAATAGC

ATTAAGGAAA

GCGTTAAGCT

GGGTATGAAT

GAATTAGCGG

ACAGGAGGGA

ATTGATTTGT

GGTAATGGCG

ATTTAATGAC

TGAGCTTCAA

TAGGTCAGGT

GCCTGTTAAA

ATGTCGCCGG

ATCCTACTTT

CTACTGCTGC

ACAATCTCAA

TCCAGTGGGC

GGTCCAGCAA

CTCTACCACG

GACTTTGGGC

GAAAACTAAT

CGCTGCTACT

120 180 240 300 360 420 WO 98/24475 PTU9I2O PCTfUS97/22104 -147-

AACAATAGCC

AAAACTTTGA

GCTAATCTCT

AACTCGTTCT

GCTTACGAGA

ACTATGGGGC

CAACATGTTT

TTGGTGCAAA

ATCAGCAATT

ACCCAACTGT

CTTAAAGCTA

TTTAACGGGT

GGCTTACGCT

TACAATCAAG

AGCCGCTCTT

GGGGACACTT

ACAAAATTCC

GACCTAAAAA

AACACTTACT

TGGGTCTATG

CTTGTTTCC.A

GTCAAAACAT

CCAACCAGCT

TAAACGCCAA

ATGGTGTTAC

CAAGCGGTGA

TCAACTCGGC

ACATCGTCALA

CAACAGGCTA

TAAACAACAC

ACCCATGGCT

TTATCACTAA

ACTACGGGTT

TCAATCTGCT

TTGGCAGTAG

ACATCAGCAC

AATTCTTGTT

GCCATAACCA

ATAAAGCTGG

GCTACGCCTT

AGGTAACCTG

CAGCAAGAAC

CAGTGAGTTG

CAACCAAGCG

CGCTCAACAA

TAGTGGGGCT

TAACGCTGGG

TAATTCTCAA

TCAAGTGAGC

CACAAACACT

TGGGAATTTC

AATCGGTTAT

CTTCAGCTAT

CACTTATGGG

GAGTCTTAAT

GCTAAGAAAC

TGATGTGGGC

GCATTCTATA

TGGCGCTGA.A

CTAA

GCTCTTTATA

ATCTTTCAAG

AACACCGCTA

GGTGGGATTT

ATCGCTTATG

GCGGGAGCGT

AACGATTTGA

AACGCTTTA.A

TATGGTGGGA

TTGGCTA.AAG

GCTGCTGGTA

AAGCAATTCT

AACGGCGCGG

GTGGGGACTG

GCGGGCTTCT

'AGCCCTCAGC

TTACGCATGA

GAAATCGGTG

GTGAAATACT

ACGAAATGGT

GCGACAACAA

GCGTTTATTT

TTCAAAACAA

TCCTAAAGCA.

TTTTAGACGC

GCGCTAAGGA

CGCTAGCCAA

ATATTGATCA.

TTACCGCTCT

ACAGCTCTCA

TCGGGGAAAA

GCGTGGGTAA

ATGTGCTTTA

TTGGGGGGAT

TTGCGAGCAG

ACTTTGGTAT

TGCAAATCCC

TCCGCCCTTA

TGACTCTATC

CACCACGAGC

GACTTACATG

CACCAATCAA

AGCTTCAATC

CGCTTTAGCC

ATTCACTAGC

CAACGCTAAC

AGCGCGCTCT

AAACAACGAG

AGTGAATGCG

CA.AGAATGTG,

TGGCCCCACT

CAATGTGTTT

CCAACTCGCA

ACCTACAGCG

CTTGAAAAAA

TACGATTTAC

TAG CGTGTAT 480 540 600 660 720 780 840 900 960 1020 1080 1140 1200 1260 1320 1380 1440 1500 1560 1584 INFORMATION FOR SEQ ID NO:53: SEQUENCE CHARACTERISTICS: LENGTH: 1380 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc-feature, LOCATION 1380 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:53:

GTGGTGTTAT

GTGAGTTTGC

CCGCAAGAAT

GAAATTGAAA

GAAGGCTTAC

GAATTTCAGG

GATGGCGTTT

AAATCAGGCG

GATGCGGTTA

AAAAATGAGC

TAACAATGAC

ATGGTGGTGA

TAGCGGCTAA

AA.AAGTATGT

TCTCTAATTT

CCCAAACCGA

TGACCGTTAT

ATAGCATTTT

ATCTCATGCG

CAAAACCCTT

AAAACGACTT

AGTTAAGGAA

AAGGGTGGAA

GGATAAGATC

GGACGCGCAT

GGGCGAATTT

TGCACCTTTA

AAAAATCAAT

CGGCAAGCCA

GGTATTTAAT

TTTAAAGGGT

AAAAAGCCGG

GCGTTCAGTC

AGTATTTCTG

TCAGCGTATT

GGGGGGCTTG

GAGGGCACTC

AACGAAAGCA

AAAACCTCTA

ATCGTTAGGG

TGTTAGGAT

TCA.,',CGGT

GTTTCTCTAA

AGATCATGAC

TGAATGAAAA

GGATCACGGT

CAGCTTACAA

CGCTGAGCAT

TTCAGATCAC

ATATTATCAA

TTCTCTTGCG

CAAAGAAGAT

TGTGGTTACA

TAAAGCGATT

GAAGTTTAAG

GGGCATGCGC

GGCTGGGGTT

GAGCATTGAT

TGTTGTTAGG

GATCCCCTCT

WO 98/24475 PTU9/20 PCT/US97/22104 148

GTCTATGTGA

AAAAATGTTA

GTGTTGGATT

CTTTTCATTA

GAATACAAGG

GGCGGTTCAG

ATCATTATCG

AAAGACGAAG

CAAGCTAAGG

AATAAATTCA

CTTGATGATA

AAAGAGGTTA

TTGAAAACCT

AAAAGATTAA

CCAAATCGGT

TGAGGGGGAA

AAGAGGGGGT

CTAATGGCAG

CGAGCGCGAG

GTGAAAAAAC

CCATTAAAAT

GGATCACGCC

GTTTGAAAGA

AAACCCCTAT

CTCCTAAAAT

GGTCTATCGT

AGACACACCT

TTTAGACGGC

TCCTGGAGGG

TTTAGTCTCT

AGCCCCTTAT

CGAGATCGTC

CTTTGGTAAG

CACGACCGCG

TGATATTGTG

AGCGGATTTA

TTCCAAAGAG

GATCAATGAT

AGATGAGAAA

TATTTGTACG

TTGAAGGCTA

CTATTAAACC

CAAAGAGGCA

ACCAATTTAC

GCAGGGGCAC

GGAAGCGTGC

CGCTATTATT

ATTTATCCGG

AAACACCATT

GCGGATAAAG

GATATTCAGC

ATGGATGAAA

TGAGAGTCAA

ACCCTAACAT

AGGCGGTAGG

AAAATAAGGA

CTGTTGTGGT

TGCAAGATCA

AAGTGTTGCT

TGCCGAGCGG

GTAAAGTGCC

TAGAGCAAGA

ACAAGAAAAG

TAAAAACCGC

AAGTGCCTAA

TTCTTTTGAT

TAAGGGCGTT

CTTGTCTAAC

GGAAAACTTA

GTTAGTCAAT

CAAGCGAGCC

CCCTGTCAAT

GCGCACCATT

AGAAAATGAA

GCTTAAAAAA

CGAAGAGGAA

TATTGACAGC

GAAGAAATAA

660 720 780 840 900 960 1020 1080 1140 1200 1260 1320 1380 INFORMATION FOR SEQ ID NO:54: Wi SEQUENCE CHARACTERISTICS: LENGTH: 315 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION .315 (xi) SEQUENCE DESCRIPTION: SEQ ID N0:54:

TTGCTTTTGC

GCCCCTTGGC

GATTTGCAGG

CTTTTCCTTA

GCAAGTGGAG

ATACGCGCTT

ACCCCTTGCA TGCTCATGCA CAAGTGCTTG GCTTCACAAA TCTATGATTT CATCAAAAGT TTCTGCAATT TGAGTGGTCA CGTTTGCTAT AAATTTCAAT GAGTTTAGCG ATCGCGCTAA GGGATATATC CCACGCTAAT ATTCCCAAAA AAAGGGAGCA TAAAATTCAA TGTTTTGAGC CACTATCATT TCATCGCAAA

TTTAA

CCACGATCAC

GCCTTTCTTG

TGCCTACAAT

AATGGTGCTC

CGCCTTGAAA.

120 180 240 300 315 INFORMATION FOR SEQ IT) Wi SEQUENCE CHARACTERISTICS: LENGTH: 498 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) WO 98/24475 PTU9/20 PCTIUS97/22104 -149- (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc-feature LOCATION .498 (xi) SEQUENCE DESCRIPTION: SEQ ID

ATGATTGAAC

AAAGAGCATT

GAGAGCCAAA

AAGCATTTAG

GACAAAGAGC

TATGAAATGA

GAAAATTTAG

AATACTTACA

AAATTTAAGG

TAATCTTACA

TAGAAAAGTT

CAGAGCTTAC

AAAATAGCTT

CTTTGAATTT

CACAAGCCTT

AGTTTGATGA

AAGTGTTAGC

CATTTTAG

CAATAAGTCC

TTATTCAAAC

TTGCAGTTAT

AGGGCATTTT

AGCTCAAATC

AAAAAATCAA

AGAACTTGTT

GAAATTTTGC

ATACAAATTG

AAAGAACAAG

TTATTGGATA

ACTTTTGAGA

AAACAAATCG

ATCATTCATT

ATTTATCACT

GTATTAAAAA

ATGAAACATT

AGACAATCGC

AAGATTTTTC

GTGAGTTTGC

GTGTTTTAAA

TAACGCAAAT

TAAATTTTAA

AGAAAGGAAC

GCTGAATGTA

AAAAACCTTA

ATTGCTAGAA

CCTACTAAAA

GGTTATTACC

TGTCAATGAA

GCTCAATCAA

ATTGCATGAA

120 180 240 300 360 420 480 498 INFORMATION FOR SEQ ID NO:56: Ci) SEQUENCE CHARACTERISTICS: LENGTH: 642 base pairs TYPE: nucleic acid STRAINDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1. 642 (xi) SEQUENCE DESCRIPTION: SEQ ID, NO:56:

ATGGATACCG

AATCTACAAG

TTTTCAAATT

ATTGATGAAA

CAAGAGACAA

GATAAAGATT

GAGAGTGAGT

ATCGGTGTTT

AAACACAAGA

CTTATTGGAT

TAATAAGAAA

CATTGCTGAA

TCGCAAAAAC

TTTCATTGCT

TTGCCCTACT

TAAAGGTTAT

AAAGTTTTTA

AACAACAACT

AACAATGATT

TGTAAAAGAG

CTTAGAGAGC

AGAAAAGCAT

AAAAGACAAA

TACCTATGAA

GCGTATTTGT

GAAACTAAGA

GAACTAATCT

CATTTAGAAA

CAAACAGAGC

TTAGAAAATA

GAGCCTTTGA

ATGACACAAG

TTGAAAAAGC

ATGAATTAAC

TACACAATAA

AGTTTTATTC

TTACTTGCAG

GCTTAGGGCA

ATTTAGCTCA

CCTTAAAAAA

TTTACAAAAA

AAGAGAAGAG

GTCCATACAA

AAACAAAGAA

TTATTTATTG

TTTTACTTTT

AATCAAACAA

TCAAATCATT

120 180 240 300 360 420 480 WO 98/24475 PCT/US97/22104 -150- CATTTAACGC AAATTGTCAA TGAAGAAAAT TTAGAGTTTG ATGAAGAACT TGTTATTTAT CACTTAAATT TTAAGCTCAA TCAAAATACT TACAAAGTGT TAGCGAAATT TTGCGTATTA AAAAAGAAAG GAACATTGCA TGAAAAATTT AAGGCATTTT AG INFORMATION FOR SEQ ID NO:57: Ci) SEQUENCE CHARACTERISTICS: LENGTH: 762 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...762 (xi) SEQUENCE DESCRIPTION: SEQ ID N:57: 540 600 642

ATGGCGATCT

ACCGCTCAAG

CTGGATAAAA

CTCTATGGTT

CCTACGGATT

GATGGCTATT

GAAAAATTGC

GGCATGCATT

GTGCCTTTcG

ATCCCCAACT

ATGGTGTTTT

GATAAGTGGA

GCCATAGTTG

CTATTAAAAG

CGTTAGCCCT

TGGCTGAAGA

TCCCTAACTC

ATGTTTTACA

ATGGCGATTC

TCGCTTGCTC

TTAAAGAGTT

AGGGATTTTG

ACCTAGAAAA

GTTTAGAGCC

GCGTGGTTTC

GCAATAAAGC

CCCAAAAGAA

TTTAGAGCGA

TTTTATCAAA

TGTGTGCATG

AGAAGGGGAT

AGCCCTCACG

TAAAGAGAGC

GAGTCAGATT

CGGGCATGGC

AGGCGTCAAA

TATGGTGTGT

AGTGGATGGA

AGTGATTCTT

ATCAAAGCCC TAAGAAAAGC GAAGTAAGGC CTGGGGTTTC TCCTCGCATG CTAGGCCTGC TCCTTAAATG AGGTGGTTAT ATTATAGGCT TGGATTTGGG CTTCCCATAG GCGCGATAAG TTGATGCATG CCATTAGCTC TTAGAGGGCG CTATTACAGA ATTGGTAAAA AGCCCCATGA GCTAATAGCG GCCCTAAAAT CAAAAACAAG GCGAGCCTAA CTTAACACAA GCCACCATGA ACGGAGCGTT AA

CGGGGAATTA

ACTTTTAGAG

TTTTAAGGGG

TCATGGTATT

GGTGGAGGTG

CCCGCAAGAT

AATTAGAGTG

AAGGGGCTTT

AGAGCCAGAA

CAAAGAGGGC

AATACTAGCG

GCATACTATC

INFORMATION FOR SEQ ID NO:58: SEQUENCE CHARACTERISTICS: LENGTH: 744 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO WO 98/24475 PTU9/20 PCTIUS97/22104 -151 (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc-feature LOCATION 1. .744 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:58:

AAGCCCAAAA

CTTTTAGAGC

GATTTTATCA

TCTGTGTGCA

CAAGAAGGGG

TCAGCCCTCA

TCTAAAGAGA

TTGAGTCAGA

TGCGGGCATG

AAAGGCGTCA

CCTATGGTGT

TCAGTGGATG

GCAGTGATTC

GAAATCAAAG

GAGAAGTAAG

AATCCTCGCA

TGTCCTTAAA

ATATTATAGG

CGCTTCCCAT

GCTTGATGCA

TTTTAGAGGG

GCATTGGTAA

AAGCTAATAG

GTCAAAAACA

GACTTAACAC

TTACGGAGCG

CCCTAAGAAA

GCCTGGGGTT

TGCTAGGCCT

TGAGGTGGTT'

CTTGGATTTG

AGGCGCGATA

TGCCATTAGC

CGCTATTACA

AAAGCCCCAT

CGGCCCTAAA

AGGCGAGCCT

AAGCCACCAT

TTAA

AGCCGGGA.AT

TCACTTTTAG

GCTTTTAAGG

ATTCATGGTA

GGGGTGGAGG

AGCCCGCAAG

TCAATTAGAG

GAAAGGGGCT

GAAGAGCCAG

ATCAAAGAGG

AAAATACTAG

GAGCATACTA

TAACCGCTCA

AGCTGGATAA

GGCTCTATGG

TTCCTACGGA

TGGATGGCTA

ATGAAAAATT

TGGGCATGCA

TTGTGCCTTT

AAATCCCCAA

GCATGGTGTT

CGGATAAGTG

TCGCCATAGT

AGCGTTAGCC

AATGGCTGAA

TTTCCCTAAC

TTATGTTTTA

TTATGGCGAT

GCTCGCTTGC

TTTTAAAGAG

GAAGGGATTT

CTACCTAGAA

TTGTTTAGAG,

GAGCGTGGTT

TGGCAATAAA

120 180 240 300 360 420 480 540 600 660 720 744 INFORMATION FOR SEQ ID NO:59: SEQUENCE CHARACTERISTICS: LENGTH: 1023 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION .1023 (xi) SEQUENCE DESCRIPTION: SEQ ID NLU.E3:

ATGTATCGTA

TATGGGGAGT

GGCAATAACC

ATTGCGACCC

CTGGATTTTG

TTAGAGCGGC

ACAAAATACA

AAGATTTGGA

TTGATTTTTT

CTGACACAGA

TTTTAGAGCA

CATTGCATAA

CTAGCCATAA

AATACACTAG

TAATTACTTA

CATCCATTAT

AACTTCGCTT

GGATTCTTTA

GAAATTTAAG

TAGGCTTATC

CGAAATTATC

AA-ACAGCGCC

TATATTCAAA

TTTTATGCGA

TTTGGAGGGA

GAAAATGATA

ATAGGGCTTT

GTTAAATTTT

TCCCTAAAGC

CGATTAGCGC

GCGATTATGA

GCAGTTTAGT

TCAATCCTTT

ATAATGCTAA

TCCAAAAAAG

GGTGTTTTTG

GCTTTTTAAA

AAAAAGCCAG

TATTTTAAAA

TTTAAAAGCT

AAGCGACACC

CCCCTTGAAA

120 180 240 300 360 420 WO 98/24475 WO 9824475PCT/US97/22104 152-

GATGAAGCCA

CAAGAAAGGG

GAAATTAATA

AACGCGCCCA

TTGCAAAAGC

TTGTTA.AAAG

CAGCTTTTTT

TTAGGCTACG

AAAGAAGCCG

CAAGGGCAAA

TGA

TTTGCGTGCG

CTAATTTTTT

ACGAAGATTT

TCACTTTAGA

TCATTTTAGG

AGGGCAAAAA

TATTTTTCGC

CTCCTCCTAA

GCTATAAGAG

AGGAATTGGG

CTTTTTTAC!C

GCATTTAGAC

AAGCGTTTCG

AGACATTCAA

GCTTTTTTTG

GGATGCGGAT

CCACATTAAA

AGAGATTGTA

GGTTTTTGAA

CTTTTTGTAT

CCTAAAGCGT

ATCAGCGGCC

TTTAACGATT

GAATTAAGCT

AAAAAAAGCG

ATTTTAAGGG

ACGACCGGTT

GAAAATTACG

ATTTTTAGGT

TTGACCCCCA

GGGAGAGTTT

ATCTTTTAAA

TAGACAAGCT

CCAATGCGGG

TCCTTGATAT

GGTTAGAGCG

TA.ATGGACGC

CTAAAAACGC

TATGGCACCT

TTCAAAAAAT

GAAATTCTTG

CGCTCTTTTT

AGCGGTTTTA

GGATATGGAT

TTATGATTAT

CTATTTTTAC

TAAAGAGGTC

CCTGCGTTTG

TCAAAGCATG

CATTAACCCT

480 540 600 660 720 780 840 900 960 1020 1023 INFORMATION FOR SEQ ID Wi SEQUENCE CHARACTERISTICS: LENGTH: 603 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc-feature LOCATION .603 (xi) SEQUENCE DESCRIPTION: SEQ ID

GTGTTTATGA

GTGGTTTTGT

TCTTTATTTG

TTATTGTTTG

AGCGTTTTAG

ACGCTCAACC

CCCACTAATC

ACGCCTTTTG

AATGGTATAA

CAAAAGCCTA

TAA

CAAGCGCTCT

TGCAAAAAAG

GCGCTAAAGG

TCATCAACAC

ATGAAACTAA

CTACGCTTAA

CTTTAATGCC

TTGAAAGCCC

AGGGTGTTGA

AAACGCA'TGC

GTTAGGCTTA

TTCTAGCATC

GCCCGCA.AGC

CATCGCTTTG

AACCAATAAA

TCCCACATTA

TACACAAACG

CAAACAGAAT

AAAAAACAAA

GACAACCAAC

CAAATTGTTT

GGCTTAGGGG

TTTATGGCGA

GGCTATTTTT

GAG CTTTC!GC

AACCCAACGC

CCTAAAGAGC

GAAAAGAATG

GAGAACGCCA

GCCCATACCA

TAGCGGTATT

CTTATAGCGG

AATTGACCAT

ACAACAAAGA

CCTTAGTCCC

TCAACCCTTT

TTCCTAAAGA

AAAAGAATGA

AAACGCCCCC

ACCAAAAAAA.

GATTGTGGTG

AAGCAACGAT

GTTTTTAGGT

ATACGGCAAG

TGCCACCGGC

AGAGCAAGCC

GCCAGCCAAA

TGCCAAAGAA

AACCACCCAC

GGATGAAAAA

120 180 240 300 360 420 480 540 600 603 INFORMATION FOR SEQ ID NO:61: SEQUENCE CHARACTERISTICS: LENGTH: 480 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular WO 98/24475 PTU9/20 PCTIUS97/22104 153- (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc-feature LOCATION 1 .480 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:61:

ATGCGTTCTC

GAAAAAATGC

TTGGTGGCGT

TGGCTGACTA

GGCGTTTATG

AGGATTAAGA

CGTTTAGGGT

AACCCCTATC

CAAATTTAGA

GTTTATGCCC

TTTTATTGAG

ACCCCATTTA

AAATCTTTTT

TCATTGATAT

TAAAAATCGT

ATAGGGCATG

AAAAGAAGAA

CTTGTATTGG

CGATCTTTTA

TTACAGCGCG

TGTGTGTTTG

TTATTTAGCG

GGTTTTTCTA

GCATGAAGAA

ACTGAAATCA

CGCATCTTAG

AGGGCATGCG

TTTGTTGTGA

TGCAAGATGA

GATTGCCCCA

TGCCCCTTTT

AAAAGCAAAA

TAGAAACGCT

CGTTTTTAAT

CTTTTTTACA

TGGGTTTTAT

GTTTGGCTAA

GTAGGGCTAT

TATGGTTTGT

GTCTTTTGGT

TCTTGTGCGT

CGATAGTTTA

TTCTTTATAT

CATCTTGTAT

ACTGGTTTTT

TTTATTGAAG

GGTGTTTAAA

GTTGTTTTAA

120 180 240 300 360 420 480 INFORMATION FOR SEQ ID NO:62: SEQUENCE CHARACTERISTICS: LENGTH: 705 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO.

(iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1._.705 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:62:

TTGAATACGG

GACGCTTTAA

ATCATGCTCG

GGGGCGACTT

GAAATCGCTT

TTTGACATCG

ACTTTAGCCA

ACAAATTGAT

CTTTGAGTTT

ATGATATACT

TAGTGAGTGA

CTTTAGACTA

TATCACCGAT

TAATGAAATC

TAACGCCTTG

TTTTTTAGAA

AAGCATGGAT

TGTTTATGGG

ATTGAGGGCA

CACACGCGCC

TATTTAGCTA

CCTATCTTAG

ATAGTGATGA

GAAGCCAAGC

TGCGTTTTGT

ACATTGATTT

ACGCTTTAGC

CCCCTTTAAA

ATGAAAGTTT

GGGCTTATGA

TAATGAAGAA

AAAAGATTCC

GCAAAAATTT

CTCAAAGTGT

AATCAATTCC

AGAAGACATT

120 180 240 300 360 WO 98/24475 PTU9/20 PCTIUS97/22104 -154-

CTGTCTCACA

ATTTTTATCG

TGTTTGAAAA

GCTCAAGGCT

GTCTCTGTGG

TACTTGGGCG

TCTATCAGTA

TAGATAGGGG

AAGAATGCCA

TAGAAAGCTT

AACACCATTA

CTAACAACGC

TCGCAAAGGC

GATTGAGACC

AGACATTTAT

GTGCGATGGG

TAAAGAACTC

GCCCAATCTC

AATGCGATCA

GGGTTTAGAG

ATTTTAACCC

GTGATTAGCG

AAGCGATTAA

AAAAAGGAAC

AAAGCCTAAA

CAGGGTTAGG

CCATTCTCGC

TGTATCGCCC

GCAATGAAGA

ATTAA

AGATAAAAAT

CGTGCAAACT

GCAAAATGTC

TGAATGTTTT

AATTGAAAAA

420 480 540 600 660 705 INFORMATION FOR SEQ ID NO:63: SEQUENCE CHARACTERISTICS: LENGTH: 864 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION .864 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:63:

TTGAAACAAA

GATGTCAGGG

GCGGCCGCGC

AACATCATGG

ATTGCCCTAA

TGCAGCGACA

GGCGTGGTGC

AAATTAGTCC

TGGATCACCT

GGGGAAATTT

GCCCCCAATA

ATGATCCCTA

CCCACTATAA

CAAAAAGTCG

GATGATTTGT

GCGAAATGGC

ATTTAGAACG

TCAAGCATGT

GAGCGAGCAA

GCACCGATAA

AGCTCTTTGT

GTTATGGTAA

AA.AACAAAGC

TAGATGAGGG

TTGTGCCTAA.

TCCCTACTAA

AAGATGAAAG

GCTTCCAAAC

CCCCTGATTT

TAAAATTATT

CATGGAATTT

CTTGAATTAC

GCCTATCGCT

TGTGATTAAC

AGCCGCTAAC

GAGCGCGAAC

TGTGGTGGGG

GAGTGAAATC

GGTTTCTTTT

AATCCCCAGC

AATCATAGGG

CCATTTAGCC

GCCTAAAGAT

TGAATACAGC

ATGA

AATGATCCTA

GCTTTAGAGG

GAATACAACC

GCATGCTTAA

CCCATTAACC

AACTTTAAAG

AGTCGTGGGA

CCCATTACCG

GTGCTTAAAA

ATGAAAATGA

ATTCGCCCGG

CTAGAATTTG

TACACGCTCA

AGCCATACTA

GGATGCGTTT

GCGTGGATAT

CCCTAGAATG

AAAATGAAAT

TCTACGGCGC

GCCCTTCTCA

GCGTGGTGCC

ATATTCGCAT

GCTTGAAAAG

TTGATCTCGC

GCGAAAAACT

AAGACTTTTT

CCAAACTCCA

ATAACCAATG

TTTTATTGGC

TTGTATCCAT

CATTAAAACT

CAGCCAGGTT

AACCAAATTG

AACGCAATTT

GTTTTTTAAA

GACACGATTT

AATGCATGGG

CAAAGCCCTA

CCATGAAGTG

TATTATTCAG

TGAAAAAGGC

GCTAGAGCCT

120 180 240 300 360 420 480 540 600 660 720 780 840 864 INFORMATION FOR SEQ ID NO:64: SEQUENCE CHARACTERISTICS: LENGTH: 606 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular WO 98/24475 PCT/tJS97/22104 -155- (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION .606 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:64: ATGCGTTTGC ACACTGCCTT TTTTGGTATT AATTCGTTGC

AGCGGTTGCA

AACGGGTTGC

CCTCTCCCAA

AACGCTATCC

GGCATGGGTG

CGAGCGGCTA

AACGCTCAAG

AATGCCCTCA

GTAAGCATGG

GGATAA

GTCTCTTTAA

AAGCCCCCAT

GCCCTCGCCT

CTAACACCCC

TGGCTCCAGA

TTGTTGATGG

ACACCGTCAA

TTCGTAACGC

AGCTTAAATT

AAAGCGTAAC

TTATCCCCCA

TGAGAATAAC

CATTCTCACG

ATCCACCATT

CTACCGCCAG

AGACATGGTT

TGAAATCACT

AGACGGCAGG

ACTAACGCTC

ACCAATTTCA

GATCAGCCCA

CCCAATAATG

TCGCCCTCTC

TTGGGTGAAA

TTACAAAATT

GAGACTATCT

ATTTGGTATC

TTGTCGCCAC

AGCTAATCCC

CCCCCAGAAA

TCATTAGCTC

TCATTGAGTT

AAGCTCTAGC

AAATGTATGG

CCGTGATTAA

ATAAAGACGG

GTATTTTGAG

TCTTTTGATA

CCCTTCAGCT

GAGCATTCAG

TAATCCCACT

GAATGCGGTG

TTTAGCTAAG

CATCAGAGTG

AACGAGAGTG

CTTGTGCCAG

CGGATCGAGA

INFORMATION FOR SEQ ID SEQUENCE CHARACTERISTICS: LENGTH: 1068 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: mis, -eature LOCATION 1...1068 (xi) SEQUENCE DESCRIPTION: SEQ ID ATGAGTTATA CTATTAATAA ACGCTTTTCT GTGGGTGTGG GTTTAAGGGG ACCGGGAGCT TTAATAACAC CGTTTATGTG CCTTTAGAGG GCGCTTCAGT GAGCAAATCT TAAACTTACC CAACAATGTT TTTGCCGATC AAGTGCCAAG ACTTTATTAG GCAATATTGG CTACCAACCA GCGCTTAATT GCCAAAAAGC

GCTTTATGCG

TTTGAGCGCG

TAACATGATG

CGGTGGGGAC

WO 98/24475 PTU9/20 PCT/US97/22104 -156- ATGAGTGATC AGAGCTGTCA AGAGTTTTAC

GGTTTAATCA

GGACAAGGCG

ATGTTTTCTG

ATCACAGAGC

GTTTCACTCC

AGGGTTGAAG

CCTGATTTTG

GAAACGCTTA

GGCTGGAGGG

TTAATGGGCG

GACTCTAATG

GGCGTAGCGG

ATTGGGCAAT

AAGCGAGCGC

TATCGGGGGG

TGGTGTATAA

TTGGCCCTTC

CCCAAACTTT

GGGTGTTTGA

CGAACGCCAC

AAAAAATGGT

ACACCAACAC

CTATTGATTA

GCTATACCGT

GGAGTTTCAC

TGAGAATCTT

GAATCTTTAT

GTATAGAGTG

TTCTTC.AGTT

TTTAGGGAGC

AAGCTTAGCC

GCGCACTTTT

TTACAAGGGC

AGGCCTAGCG

CTTTAGATTA

TGATCAAGCC

GGCTTTTGGG

TTTTAAGAGC

TAGCGCCTCT

AACGGCTTGA

GGCACGACTC

GGTTCGAGTT

ACCTTTAACA

GTTTTGACTA

TACGCCCACC

TGGAGTCAAG

TTGAGCGGGA

AATTTTAAAA

GGGGTAACTT

CCAAGCCCCC

ACTAAATACA

AACCGCTCCA

TTAGGCTATC

AAAAAATCAT

AAGTCGTGCA

TGCGTGTGTT

TGAAAGGCGG

AAGGCAGCTT

AATTTTTTAA

GGAATAAATT

CGGTGGCTTC

GCGTGATGAA

ACATGGGTAA

AAGACGCGAT

ATTTTAGGGG

GTTTGTATCA

GCTGGTAA

GGGTTATAGC

AAAATCTAAc

TGATCATGGC

TTTGGTGGCT

GAATATCAAT

AGATCGCCTA

TTTAGTCACC

CTTGGACTCT

CATGGGGGCT

AAGCTTGCGT

AGGCATTCCG

CTTTGATTTG

ATCCCCAACT

300 360 420 480 540 600 660 720 780 840 900 960 1020 1068 INFORMATION FOR SEQ ID NO:66: SEQUENCE CHARACTERISTICS: LENGTH: 1764 base pairs TYPE: nucleic acid STRAN'DEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1 1764 (xi) SEQUENCE DESCRIPTION: SEQ ID N0:66:

ATGAAAAACT

CTGAGTCTGC

GGCACGGCTT

AACCCGGCTA

ACCACCACCG

TTATATTCGG

AACACTATAG

TTA..C.,CAAG

ACCCTCGCTT

GTTTTACCTA

TTTACCGCTC

GACGTGTTTA

TTTTCTGTGG

TATGTGCCTT

AATGTTTTTG

CAACCAGCGC

TTTCCCCACT

CCTTGCTTTC

TAGGCTCGGC

ACATGGGCTT

TGATCAATAT

TAACAAGTTT

GGTTAGGCAA

CTATCAATCG

CAAAACCTGA

AATTCTTTTA

CTAGTGGGTT

TCATGATGGT

GTGTGGGTTT

TAGAGGGCGC

CCGATCAAGT

TTAATTGCCA

CTATTGTCTT

TTATGCGAAT

GTATGTCGCT

TACTAACGAT

CCCGGCCTTT

AGAAATTGAT

TATCCTTAAA

TGTTCAAGGG

CACTCAAATC

TAAAACGCGC

GGGTATGAAA

AGAGCTTGCC

AAGGGGGCTT

TTCAGTTTTG

GCCAAGTAAC

AAAAGCCGGT

AAAAAGCTCA

GGCTTTAAAA

GGGGCTAGGG

TGGGGCGAAA

AGCTTTAAAG

AAAAGCCAAC

GCGCTTGGCA

CTTATGAACT

GTGAATGGCT

ACGCATAACG

TGGAATGGTA

CCTAGCATGA

TATGCGACCG

AGCGCGGAGC

ATGATGACTT

GGGGACATGA

AAAAACGCCA

TCCAAGAGCA

GTGCTGACGC

ACAGAAGCGA

TCCCTACGAC

AAAATATTTT

ATACGGCCGC

TAACCAATCA

GGACAGGCAC

GCTTCACTTT

AGGGGGGGGA

GTTATACTAT

GGAGCTTTAA

AAATCTTAAA

TATTAGGCAA

GTGATCAGAG

TTTAATCGCT

AAGCTTGAAT

TTCTTTTTAC

ATTTGAAATG

CAATCAAGGC

AGGCATCATC

TACCAATGGC

AAAAGTCGTA

GACTAATTTT

TGGGGGGAGT

ATTTTTGCAT

TAATAAACGC

TAACACCGTT

CTTACCCAAC

TATTGGCTAC

CTGTCAAGAG

120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 WO 98/24475 PTU9/20 PCTIUS97/22104 -157- TTTTACAACG GCTTGAAAAA AATCATGGGT TATAGCGGTT CTTTATGGCA CGACTCAAGT CGTGCAAAAA. TCTAACGGAC

AGAGTGGGTT

TCAGTTACCT

GGGAGCGTTT

TTAGCCTACG

ACTTTTTGGA

AAGGGCTTGA

CTAGCGAATT

0 AGATTAGGGG

CAAGCCCCAA

TTTGGGACTA

AAGAGCAACC

GCCTCTTTAG

CGAGTTTGCG

TTAACATGAA

TGACTAAAGG

CCCACCAATT

GTCAAGGGAA

GCGGGACGGT

TTAAAAGCGT

TAACTTACAT

GCCCCCAAGA

AATACAATTT

GCTCCAGTTT

GCTATCGCTG

TGTGTTTGAT

AGGCGGTTTG

CAGCTTGAAT

TTTTAA-AGAT

TAAATTTTTA

GGCTTCCTTG

GATGAACATG

GGGTAAAAGC

CGCGATAGGC

TAGGGGCTTT

GTATCAATCC

GTAA

CATGGCATGT

GTGGCTATCA

ATCAATGTTT

CGCCTAAGGG

GTCACCCCTG

GACTCTGAAA

GGGGCTGGCT

TTGCGTTTAA

ATTCCGGACT

GATTTGGGCG

CCAACTATTG

TAATCAAAGC

AAGGCGTATC

TTTCTGTGGT

CAGAGCTTGG

CACTCCCCCA

TTGAAGGGGT

ATTTTGCGAA

CGCTTAAAAA

GGAGGGACAC

TGGGCGCTAT

CTAATGGCTA

TAGCGGGGAG

GGCAATTGAG

GAGCGCGAAT

GGGGGGGTAT

GTATAATTCT

CCCTTCTTTA

AACTTTAAGC

GTTTGAGCGC

CGCCACTTAC

AATGGTAGGC

CAACACCTTT

TGATTATGAT

TACCGTGGCT

TTTCACTTTT

AATCTTTAGC

1020 1080 1140 1200 1260 1320 1380 1440 1500 1560 1620 1680 1740 1764 INFORMATION FOR SEQ ID NO:67: SEQUENCE CHARACTERISTICS: LENGTH: 618 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genornic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc-feature LOCATION .618 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:67: TTGATTTTTA GATTTTTCTT GATTGGAATT TTTTCAAACC GGCTATCTTT ACCAACATGC CCGCCTATTT TAATGGATAA GTTTTGAAAA AGAAAGCTTT TTCATGAGCG CTGGGCTAGT ATCGCCTTAG GCTATCAGCT ATCCAATCAG CGGTGGGGAG AGTATAGAAG CAAGGGGCGG TTCGGCACGC CACGATTGAA ACGAGATTTT TAGGGTAA

AATCTTAAGC

TTTAGAGCCT

AGAAACGACT

AATTTACCAT

ATTGGGGGGG

CGCTGGGGTG

TCAAATTTTA

TGTGGGCTTG

TATCCCTTTT

TATCTATTCT

CTTTTAAAAG

ACTAAAAAAT

AAAAGATTCC

GACGCTTCTT

TATTTGGATG

AGGCTTTTTA

GGGGCTAAGA

TTTTTCAATG

TATTTCATTC

GTTGGTATCA

GGGTTTTACT

ATTTTGGCTC

CCATCCGCCC

TGGGTTTTGA

CAGGAATGGG

AGGGGTGGGT

TTGATAAGTA

CGGCTAAAAA

AGAGCAGGTT

CATTCACTTT

GGCCAAAAAG

TTTTAAAATC

TAAAAACCGC

CGCAGGGTAT

CGATTCGTAT

TATCCCTAAA

TCAATTCAAT

TTTTGGCTTG

TTCTAAGGCT

TTATGACTTT

120 180 240 300 360 420 540 600 618 INFORMATION FOR SEQ ID NO:68: SEQUENCE CHARACTERISTICS: LENGTH: 762 base pairs WO 98/24475 PCT/US97/22104 -158- TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 762 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:68:

TTGTGGCATG

AGGGATTGCG

GGTGTTTTAT

AAAAGCTTTA

GCGTTTGAGC

AAAATAACCC

GGGGGGTATC

ATGGCGATCA

GATGTGTTGA

GGGATAGGGT

TATAACGGCT

CTTGGGGCTA

GAGAGCGTTT

CTGCCTTTAG

ATGAGTGGGG

CGTTTGCTCG

GAATGAAAAA

CTAAAAAAAG

CAAAACCGGC

AATTCGCTTT

AACCCACCGC

GCGATTTTTA

ATTTTTATCA

TGTTTAATGT

AGATCCCTTT

TTATCCATGC

CGTTGGCGAG

GCTTGATGAT

CTCCCATAGA

AATTGCTTTC

TCATATTTAT

TAGTGATTCT

TTTTAAAGCT

ACTGCACACG

CACTTATAAA

AAGCAACCAT

GGGGCTTGGC

TTCAAAGACT

GGCTTATAGT

TGGGGATGGA ACGGCGATGA TTCTATGGTG TTAAGCCTAC CGACAAAATC AAGCGGTTTT ATTTTGGCTT TATGGGTGGG TTTGGGGCTA TGGTGGGTTT TCTTATACGG CTTTTTTATG CTAGCGTTAA GGGGTGAATT ATTAACACTT CTTTATTGAG AAATACAGCT TTGGGGTGTA TTAGGCATGA AAAATAGTTC AGCACGATCG ATCGCCACCA AGAAATTCTT TTAAAAATTC TATATGTTTT AA

AATCCCCTAT

TGATTGTGCC

ATCAAAACCA

CTTGTTAGGG

AGCCCCTGTT

GGGGGCTAAA

TTCCTACCTT

TTTAAATATG

TGGGGGGCTT

GTTTATGGGT

CCGCGTAGAG

TTATTTTTTA

120 180 240 300 360 420 480 540 600 660 720 INFORMATION FOR SEQ ID NO:69: SEQUENCE CHARACTERISTICS: LENGTH: 1239 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: miscfeature LOCATION .1239 WO 98/24475 PTU9120 PCT/US97/22104 159 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:69:

ATGGAATCAG

ACAGAGGCAA

TCAATTGGTG

CCCAAGAAAA

GAATTGGACG

TGGTGGAAAT

GGTGATATTG

ATAAAGTTAG

GAGATAGAGT

AGTCAAATAA

AAGAGTGAGA

ATTAAAGAAC

CAATTGTTTA

ATAGAAGCTG

AAACACCTCC

ATCGCTTATT

CAAGTGGATT

AAGGTTACAG

ATGCTTGAAA

CAAAAAATAT

ACAGAAAAAG

TAAAAACAGT

GTAAAGAGAC

GGATTTTTAC

GCAGTGTGGC

ATAAAGTCCA

ATTCAGGATT

ATAAACAAAT

AACAAGAAAG

TAGAACAAGA

AAGCAGAACA

TAGAGTTAGA

AGAAAGATTT

TTAAAAAAGC

AATGCAAAAC

CAAACTCTAA

TGCAAAAAGA

TTTATAAACC

AAGAATGGCA

TGAGAAACCC

TTGCTGATAT

CGGGTTATGG

AAAAACAAAT

TCATTTTAAA

AAAAATTOCA

ATTAGTAGTA

AGATAAATCC

AACAATAGCG

AGAACTAGAA

ACAGAAAACA

AAGACAAAAA

AGAAAGACAA

ACAGCAAAAA

CATTAAAGAA

AAGAATTAAG

CCCTAAACCT

ACAACCCCGC

GCTAGAATCT

AAGTTCTATC

AAAAGAAAAT

ACAAGCCCAC

TAArAAAGAA

TTATAGTAAA

AAAGTTGGCA

CAAGCGAGTG

AAGAAAGTTA

TTGACCCATA

AAACAAGCTG

GCAAGTTTAT

CAAGAAAAAA

GAACAAGAAA

ACAAACAAGA

AAGACAGAAC

CAAAAGACAA

ACAGAACAAA

ACCGGTATTA

GCAAAAACCA

TCTCAAAGAG

CTGCCCTATT

GCTTATTTAG

TTAAAAATAC

CTTCCAACCT

ATAGAAGCAG

AGGATGTAG

AAAACACAGA

CCATTACAAA

GAGAACTTGT

TTGCGTGCAA

AAAAAGAAAA

TATTAGCCGC

AGGAAGCAAA

GACAGAAGAC

GTGGGATAGA

AAGAAAAACA

TTAATACACA

ATTGCCAAGA

CTACTGGTAT

ATCAAACCCC

GATCAAAAGC

CGCAAAAAGC

AACTAGACCC

GCTCTAAAGC

CTCAAAGCCT

TTGCTAATAC

GACAGCTAAC

TACGCTCCGA

GAAAAAACAT

GAGGGCAAAA

TCAAATCAAT

TTGTAGCACT

TA1AGAGTGGG

AAATAAGAGT

ACTCGCTAAT

AAAAGCAAAT

AAGAGATTTG

AAAACATGGC

TGCCATAGAA

TATCCAGCCA

GCAAGAGCTT

TATCGCTAAA

TAGAGATTTT

TCAAGCTAAA

TTTGTTCGTT

TGAAAAGAAA

120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1140 1200 1239 INFORMATION FOR SEQ ID SEQUENCE CHARACTERISTICS: LENGTH: 450 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION .450 (xi) SEQUENCE DE 2 ;C.,,IPTION: SEQ ID

TTGAATTGGG

TTGGGGCTTT

CAAGCAGGGA

TTAGAAGCGA

GATAAGAATT

GAAGTCATTG

GATTTGCATG

AGCATTTGAT

TTTTGAATGC

AAGTCGCTCC

TGAAAGAAGA

TGGCTTCTTT

CTAACAAAAA

ATTGCGCATG

GAAAAAATTA

GAGTGATTT

TAGCGAAGTT

AGAGCGTCAA

AAGCCAAGAA

GAAAACAATG

CGAAGGCCCT

GCGTTTTCTT

AAGAGCATGG

CCAGAGTTTC

AAATATAAAG

GATCGCAACA

ACCATGAAAG

TTTCATGATC

TATTATTTAC

ATAACAAGCA

GCACAGAAGT

CGGATTTTAA

AGCGTAAAAA

AGTATCGTGA

ATGAAAAAAA

AGGGACTTTT

ACTATTAGAG

CAATAAACGA

GAAAGCGATG

AGAAATCCTT

AGAGGGGTTG

GGGGCAAAAA

WO 98/24475 PCTIUS97/22104 -160- GGGAAAAAAC CAAGCCATCA TAAGCATTAG INFORMATION FOR SEQ ID NO:71: SEQUENCE CHARACTERISTICS: LENGTH: 615 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...615 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:71:

ATGCAAGCAG

TTACAAAACG

CAATTCAAAC

TGATTTTAGC

CTCCCTTTTT

CCAGCGTTGT

TTGTATAACC CTATA( TATGCTTTGA ATAGG( GACCACGCTT TAGCG CAATCCGTAA GCGAT TTTAAGGGGG AGCAAJ AACCTCAAAT ACCCC GAAGCCACTA ATCAT: CAAAAATTCT CATGA

CGCGT

GGTTG

AACAC

TATGG

ATCTC

TTAAA

rGTTT

GAATGGGGAG

AATCGCATGC

TATAGGCGAT

GAGCGAACAA

TGATGATTTT

TTTTTTATTG

CCTTTTTAGG

GCTTTTTAGC

AGACTTGCGT

TAGCCTTAGC

TTGGATAGCA

GACAGCAACG

ATTTTTTTAG

TTGGAGTATT

GTGTTAGAAA

TTGGATCTTA

CTAAAAACGC

TCTGAACCTA

TTTCCTAAAT CTAAAAAATG GATGGGGCTG TTATATCATT

TTGATTCGCA

ATTTGTCCAA

GGTTGAATGG

TTAAATTTTG

CCCCTTTTAC

AAGCCCGATT

TCTTTTCCGG

AATCGGTGGT

CTTAGACATT

GCATGCGCTT

TTTGAAAGCC

AGCCTTTTTT

CAAGCGAGAA

CAAAAAAATC

TTTGCCCAGT

CACTTCTAAA

CTCGCTCAAT

GCTAGTGTAT

120 180 240 300 360 420 480 540 600 615 INFORMATION FOR SEQ ID NO:72: SEQUENCE CHARACTERISTICS: LENGTH: 843 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori WO 98/24475 WO 9824475PCT/US97/22104 161 (ix) FEATURE: NAME/KEY: misc-feature LOCATION 1 .843 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:72:

GTGTTTGACT

GTTAAAAATA

GGTTTTATAG

CGACAAGGAA

GCGATCTATT

TTCTACGCCC

GCGTTCATGC

ATCCCCTTTA

GACTTTTTAA

AAAAAAGAAA

AGAGAGATTT

GCAAGCCTTT

CATTGGGCGG

TAAACGCTTG

AAAATCCTAC

CAAGGCACAA

TCTCCATCCG

CTTATGATGA

TTTTTCACAC

GCGAAGATGA

AAGGCGAAAT

ACAAGCCCCT

ATCGCTATTA

ATGACATCAA

ATTTTTGGGG

GATAAAAAAT

GCCTGATTTC

TATAAAACTT

TACGATAATA

CAAAATAATA

CAATTATCTT GGTTTAACCT

CCATTGCATC

CGCTTTCCAA

CCAAAACCGC

AGTTGATTCT

CAAAGAACCT

AAAATTCAGC

CCACACACAA

AGAATTTTTT

TGAATATTAC

AATACAGCCT

AAAGCCACAT

GACGACAGCG

ATCACTGCCA

AAAGAAAGGT

AAAAAGAGCG

TCGAGCGCTT

GATTTCATCC

CAAGGCCGTA

AAACAGCTTT

AAAGTCTATG

TTAAGCCGAT

AAAAAG CT CA

AGTTTTTGTG

CTACAAACCT

GGCAAAACGA

AGTTTAAAAA

CTCAAGGGAC

ATTTGAGCCA

ATAGCCTCTT

CAAAGGTGTT

ACACCCCCTA

ACAAGCAAGG

ACGCTAACTT

AATACGGATT

AGTGGATAAG

AGAGATTATG

TGTTTTAAAC

TCTAATCGGC

TAGGGATCAA

CAATTGTTTG

TAACCATTTT

TGCTTTATTA

TTTAAACGCC

TGACGCTGGC

TAACGCTAAC

CAGATTAAAC

GCAATACGCC

TTTAAGGGAG

120 180 240 300 360 420 480 540 600 660 720 780 840 TCACCCACCA AAGCCAAAGA CTAAAAGATC TCGCCAAAGA

TAG

INFORMATION FOR SEQ ID NO:73: SEQUENCE CHARACTERISTICS: LENGTH: 930 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION .930 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:73:

TGTGACAGGG

AA.ACCAACCA

AAAACTTTTA

GATAATAAAA

AATAATAAGT

TTAACCTCTA

GCCACATGGC

GACAGCGAGT

ACTGCCACTC

CAATTCCCCA

ACGCGTTCAA

AGCCGATAGT

AAGCTCAAGA

TTTTGTGTGT

CAAACCTTCT

AAAACGATAG

TTAAAAACAA

AAGGGACTAA

TTGGCTTTTT

TTTAGAAGTG

GGATAAGGTT

GATTATGGGT

TTTAAACCGA

AAiTCGGCGCG

GGATCAATTC

TTGTTTGGCG

CCATTTTATC

AGTCTGGGAT

TTTGACTCAT

AAAAATATAA

TTTATAGAAA

CAAGGAACAA

ATCTATTTCT

TACGCCCCTT

TTCATGCTTT

CCCTTTAGCG

ACCGCTACCC

TGGGCGGATT

ACGCTTGGAT

ATCCTACGCC

GGCACAACAA

CCATCCGCCA

ATGATGACGC

TTCACACCCA

AAGATGAAGT

cccccc,.r.A

TTTGGGGTAT

AAAAAATTAC

TGATTTCCAA

TTATCTTGGT

TTGCATCAAA

TTTCCAAGAC

AAACCGCATC

TGATTCTAAA

120 180 240 300 360 420 480 540 WO 98/24475PCIS7214 PCT/US97/22104 162-

GAAAGGTATT

AAGAGCGATA

AGCGCTTCAA

TTCATCCACA

GGCCGTAACA

CAGCTTTACG

GTCTATGAAT

TGAGCCATGC

GCCTCTTTTT

AGGTGTTTGA

CCCCCTATAA

AGCAAGGCAG

CTAACTTGCA

ACGGATTTTT

TTTATTAGAC

AAACGCCAAA

CGCTGGCAGA

CGCTAACGCA

ATTAAACTCA

ATACGCCCTA

AAGGGAGTAG

TTTTTAAAAG

AAAGAAAACA

GAGATTTATC

AGCCTTTATG

CCCACCAAAG

AAAGATCTCG

GCGAAATCAA

AGCCCCTAAA

GCTATTACCA

ACATCAAAGA

CCAAAGATGA

CCAAAGAAAT

AGAACCTAAA

ATTCAGCTCG

CACACAAGAT

ATTTTTTCAA

ATATTACAAA

ACAGCCTAAA

600 660 720 780 840 900 930 INFORMATION FOR SEQ ID NO:74: Ci) SEQUENCE CHARACTERISTICS: LENGTH: 564 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc-feature LOCATION .564 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:74:

TTGGAAACTT

ACTAGAAACA

AAAATTAGAA

GAAATTAAAG

CTCTCGCACT

AAAACAAAAC

AACAAATTGG

AGAAAATCTT

AACAGCGTTT

TTAAAAATCG

ATATCATTGA

GCAATGATTT

ATATTCTTAA

AAGCCTTTTT

CGCATGCGGA

GCAAAGTGTT

CAAAACACGA

TACAAGATAT

CTAATCAAGG

CTTCATTCTA

TGCAGATAAT

TTCCATGTTG

AAAACATGGC

TAGCCCGTTC

TAAAAATAAG

TATCGATTCG

TGATATAAGC

GATTGAAAAA

GCTATCACGC

TTAG,

ATAGATGGGG

CCCGTTTTTG,

AGTAGAAAAG

AAACCGCAGC

GCTTTAGGGG

CTTTTTTGGG

AAGATTGAAG

TGCCCTTATT

ATCACTTATT

ATTTATTTTT

AACTCGATCG

ACATTATTTT

TAAAAACCGT

TTAAGGACTA

ATTATAAAGA.

ACGCTTTCAC

TTGTGTTTTT

CCGCATGGAT

CTATAATCTT

CATTGCCCAA

AAAACACAAT

TCAAGTGTTC

TTTGGAA.AGC

CGATGTTTTA

GCTCATTCTC

ACAAAGCAAG

TTATGAAGAA

INFORMATION FOR SEQ ID SEQUENCE CHARACTERISTICS: LENGTH: 597 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO WO 98/24475 PTU9/20 PCTIUS97/22104 163- (iv) ANTI-SENSE: NO ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NME/KEY: misc-feature LOCATION 597 (xi) SEQUENCE DESCRIPTION: SEQ ID

TTGGAAACTT

ACTAGAAACA

AAAATTAGAA

GAAATTAAAG

CTCTCGCACT

AAAACAAAAC

AACAAATTGG

AGAAAATCTT

AACAGCGTTT

ATATCATTGA

GCAATGATTT

ATATTCTTAA

AAGCCTTTTT

CGCATGCGGA

GCAAAGTGTT

CAAAACACGA

TACAAGATAT

CTAATCAAGG

TGCAGATAAT

TTCCATGTTG

AAAACATGGC

TAGCCCGTTC

TAAAAATAAG

TATCGATTCG

TGATATAAGC

GATTGAAAAA

GCTATCACGC

ATAGATGGGG

CCCGTTTTTG

AGTAGAAAAG

AAACCGCAGC

GCTTTAGGGG

CTTTTTTGGG

AAGATTGAAG

TGCCCTTATT

ATCACTTATT

ATTTATTTTT

AACTCGATCG

ACATTATTTT

TAAAAACCGT

TTAAGGACTA

ATTATAAAGA

ACGCTTTCAC

TTGTGTTTTT

CCGCATGGAT

CTATAATCTT

CATTGCCCAA

AAAACACAAT

TCAAGTGTTC

TTTGGAAAGC

CGATGTTTTA

GCTCATTCTC

ACAAAGCAAG

TTATGAAGAA

TTAAAAATCG CTTCATTTCT ATTAGCGCTA TTAACGAGAG TCGCCCAATT CCAATGA INFORMATION FOR SEQ ID NO:76: SEQUENCE CHARACTERISTICS: LENGTH: 570 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NME/KEY: misc feature LOCATION 570 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:76:

ATGATGACTA

TGCGCCAAAG

TTTTTGAGAA

TTTTTGTATG

TCCATTTGGG

TTGAATTTGT

AAATTGCTCA

AAAACATACC

GTTCGCCCCA

A P-CGCTTA

ACAAGGGGCT

GTTTTAAAGA

ACTACCAATT

ACAGAAAGCT

CTCTTAAGAT

CCAACGCTGA

ACCAAAGCCA

CAACACCCCC

TGCGTTTGTC

AATCCCTATC

GCGTTGCAAT

TCCAAGCGAG

TGTGGTAGTG

AGAAGATAGG,

TTTGGGGAGC

GCAAGAAAAA

TAGCTATGGG

GTGATTGAAA

ACTGAAGGCT

CTGGATTTTT

GTTTTTTCAT

CTAGTGGAGG

CATTCTAATA

AACCACAAAC

TACAAAAGAG

GGTGGGAGCA

AAAGTATTAT

TTGTGCCGTT

TAGAAAATTT

TGTGTAAGGA

CTTTGGAGGG

GCTTGGGTAA

CAATCGTAAT

AAAGAGGCGA

TTAGAATCAG

GGTGTTTAAA

AAAAGAGGGC

AGACCTTTTG

TTTGAAAAAT

TTTTAAGGGT

TGGCGTTCAA

AGACAGCATG

AACGCTAGAG

CGGCGATAAA

WO 98/24475 PTU9/20 PCTIUS97/22104 164- AAGCCTGATT CCAATGAAGA AAATTTTTAA INFORMATION FOR SEQ ID NO:77: Wi SEQUENCE CHARACTERISTICS: LENGTH: 1773 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION .1773 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:77:

ATGAAAGCGA

AGGGCGTTGT

GATTTTGGGG

AATGCGGCTA

TCTGGTATCT

AAGAATTTGA

GGTATTTATA

GCTGATTTGA

AGCCCTTATT

TATGGCATGT

GACTTTTATG

GACTACTTGA

GACGCTTCCA

AAATCTTCGC

ATTCAAACCA

GACAATTCGC

CAAGCTAAAG

AGTCCTAATA

AACAACCTCA

CAAGCCCAAG

GTAGGGAATT

GATGCGATCA

AACACCCATG

GCCACCAACG

GCAAACGACA

AACACCGACA

AGCAACATGA

AACGACATGG

AACGATGACA

TAAAAATACT

TTGATTTAAA

GTTATAAAAG

ATGGCGATGC

TGGGGAATTT

AATATTGCCT

TCCCCTTAGG

GCGTGGTAGG

ACAGGAGCAA

ATGGAATGGG

ATGGCATGTA

TGTTAGAAAA

TCAACCAACT

AACCAGCGAA

ACCGCTTGAA

TCTTCCACAC

AGCTTAACCA

AGATTGATTC

ACCAACTAGA

TGGATAAAGC

ATTTAGACGG

ATAACCCTAT

CAAATGACAG

ATGATCACAA

CCCCCACTGA

CCGGCAATAC

ACAACGGCAA

GCGATGACAT

TGGGCGATAT

TCTTATAATG ACACTCAGTT AGATTCGCAA. TTAAAAGGGG

CAACACCACA

GAAAAAATTC

TAGAGCGCAT

TAAAATCATC

CATTTCTTTA

GGCGTATCTT

CAACTATTAC

CATGTATGGA

TGGGTTCTAC

TTACATGTAT

TGATACGCCT

TCTCATGAGC

TAGCGCCTTA

TAAAGCCATG

TTTGGTGGGG

AGTGGTCAAT

CAATGACTTA

CTTAGACAGC

GAGTTTGAAA

GCAACAACCT

CAAAGATCAA

CGATGATCAC

TGATAAAGAT

GGACACTGGC

CGATGATACG

GAATAACGCG

GGGGGACATG

GAGTGGGGAG

AGCGCGTTAG

GCACATTTGA

GCTAGGGATT

AAAGATCAAA

AAAAAGCAAC

AACTCCTACT

'ATGTATGGCA

C!CTAACATGT

GCACTCGATC

ACTGATGATG

TTTTATCGTG

GTCAATTTAG

CCCACTAAAA

CAAATCAAAG

AAAGCTATGG

AAAGATCAAA

GTGCAACAAT

ATTGATGGCG

GCGCAACAAA

GGGGGTAACG

ATGGACACTA

GCTAGCGGCA

AACACCGACA

GGTAACACTA

AACGACATGA

AACGATGACA

TAAACGCTAT

AATTAACGCC

CTACGGCTTT

TGGAAAAAAT

GGCAAGCCCT

CTTTTTATAG

AAACGGCTCA

AGGAGAATGA

ATAGCCCTTA

TGGGCATGTA

TTTTCATGAT

AAGAAGAGAT

ACAGAGACGA

ATCCCAAATT

ACAACAGCCA

GCGTGGATGC

AGATGAAGCA

AGGTTAGGGA

AAGGGCTTTC

TAAGCCATAG

ATGACAGAGA

CGCCTATTAA

CGCTCATAAA

ACACCACTGA

ACAATACCGG

CCGGTAACAC

ACGACGACAT

TGGGTGGCG.A

CAGCGTGAAT

AAAAATAGTG

AAACTATATC

GCGTTTTAAC

AAAATTGCAA

TTACCGCACC

AAAAATGCTC

AAAGGCTCAA

TTATGGCATG

TGATTTTTAT

GCAAGTTCAA

TTTAGACCAT

TAAAGACGAT

CAGCAAAGAC

CATGCTCAAA

GATCACTTCT

AGACGGGGCG

CAAATTAGAC

AAGCGAGCAG

CAGCGATGTG

CGATTTGAAT

CAACATGGAC

CCCTAACAAC

CACTAGCAAC

CGATATGAAT

TGATGATATG

GGGTAATAGC

GGGTAACAGC

TATGGGAGAC

120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1140 1200 1260 1320 1380 1440 1500 1560 1620 1680 1740 WO 98/24475 PCTIUS97/22104 -165- ATGGGGGATA TGGGTGGCGA TATGGGGAAT TGA INFORMATION FOR SEQ ID NO:78: SEQUENCE CHARACTERISTICS: LENGTH: 588 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: miscfeature LOCATION 1...588 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:78: 1773

TTGAATTTAC

TTTTTAAAAA

ATGAACCATC

GAAGAAGAGC

GCCAAAGAGC

CCAAAGCCCA

GGGAAAGGCT

GCAATTGAAG

GAATTGGAAT

CTCATTTTAG

GATTGGCTGG

TGTTTGACAA

AAGTGTATGA

AAGACTCCTC

AAGAGCAAAA

AAAGCTCTAT

ATTGCAACCG

ATAGCGGGAT

TTATGGAGAA

ACAACCAAAA

AGCAAGCGTT

AAAACTTTCT

CATTGAAACC

TTTAAATACC

AGAAAAAAGG

GGGAGAGTTT

GTATTTTGCT

TTCAAGAAAA

TTTTAAGGGT

AATGAAAATT

TTAACGGCTT

AGCAACGATT

ATGCTCGCTG

GCTTTGCCTG

AAACACTGGT

GTGTTTGATC

AGCTACACAT

GTGTGTAGAG

AATTTTGCGG

TATTTGAAAA

GTGTCTTTTC

GGCATATCCA

ATAGCGCTTT

AAGATAAAAC

ATGAGCTTTT

AAAAAGAAAA

GGCAGGGCGA

ATGAGCATTT

TAACTAAGGG

CGCCATGA

GGGGTGTTTT

AAAAGTAGAA

TAGAGAGCAT

AGCGATTGAA

TAAAAAGAAG

TCGTATTTAT

TAGGCACATC

GATGGCGTTT

CAAGGACACG

120 180 240 300 360 420 480 540 588 INFORMATION FOR SEQ ID NO:79: SEQUENCE CHARACTERISTICS: LENGTH: 2235 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: WO 98/24475 PTU9/20 PCT/US97/22104 166- NAME/KEY: misc-feature LOCATION .2235 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:79:

ATGTTAAAAC

GAAGCCTTTC

CTATTACAAG

CCCAAACCCA

CAAAGCACCA

ACCTTTTACT

GCTGGCTATG

AACATTGAGC

ACTATCCCTA

AACGCCGATG

CAGAATCTGT

TACAACCAAT

AACCAAGCAA

ACCAATTTAA

TTAAACGCTC

CTTACATGCG

AAAGGAGATG

GATGTTATCT

GGAGGGGATT

ACCAATTTTG

AAAGAATTGA

ACTTTAGGCT

AACAATGGGC

GTGCAAGTGT

TGTTCTCGTT

GATTGCTCTC

ATTGATCAAA

AACGCCAGCT

CTTTCATCTT

GGAGCCCCCC

CTAGGGTTGT

ATCCAGCAAT

ACTAACGAAA

GTGTTTGGGG

AGCGGTAATT

ATAGGCATTA

TATACCAATT

GGGTGGATTT

TCGCCAGTAA

AAAAACACCA

GCACACAAAC

AACCAAAACC

TTTTAAAGAA

CTCAAAACCC

GTAATAACAG

TGAGTTACAC

AACAATCTCA

GCTTCCAACA

TTAACAAGCT

TTTCTAGCGG

ATTGTGTGGC

TGCTGAACAT

CTTTCCAATT

TGAATCCTTA

AATACAATAT

ATAGCTATAG

TAGGGTTAGG

GCGCTTTAGG

ATAAAGTCGC

ATACGCATAA

CAGAAGAGCG

TTGACAACGG

TTAAAGATAA

AAGTCCCCGC

ACGCCCTACC

TGAACACGCA

CTAAATCTAG

TATTAGGCGT

CTTCTTATGG

TAAGCTATGG

AGAACCCCAA

GGTTAAGGGG

TAAATGTGAC

GCGTTCCTTT

CTATCACCCT

TCTAA

AACGATTTGT

AAAAGACGGC

CCAAGAACAA

CATTACCCCT

TGCGACTGAG

TGTGTATGTA

CTTGATTATG

GGACGATCAA

AATCATTCTG

ACTCCAAACC

CAGCAAGGTT

TAACGGCAGT

TAAAGTGCCG

GATGGCGGTG

CAGCGACAAC

CAACGATGGG

AGAAAACGGG

AGTCGCTAAT

GTCTCAATAT

GATATTGTCC

CATCATGCAA

CGGGAACATG

CTGTCAGGGC

GCATGAAGTG

GCCCTATACA

TGGGCTTATA

GGTGGATTTT

AGACTTTGCG

CGCCACTACT

TAATCTTAAA

CATTATCAAA.

CGTGGGAATG

AAGCAATCTA

CTTATACAAC

CGGTGGGTTG

GGTCCAGTTG

CAATGAAGGG

TTGTCCCTAA

TTTTTCATAG

ACCATAGCCA

CAAAGCACCT

TTGTTTGCAG,

ACCGCTTATA

ATACAAAACT

GGCAATGTGG

CCCGCAAGCT

AACACCACAC

ACAACCAATC

GGCTCTAAAC

CCTTTCACCT

TTTGATTCTA

AACCTGTCAG

CTTGTTGATC

CAAACAGGCT

AATATTTATG

GGTGGCCCGA.

CCTTTCTTAG

TTAAGAGACA

ACTTATCAAA

GGAAGGATAG,

CGAGACACCG

GCGGGCAGCT

GGCGTTACCA

ACTAATTTGA

ACCACCATGC

.TATCGCACTT

ATGGGCTATC

TACAACTACG

GATGTGCTGT

ACCAAGAAAG

AGCTATTATT

AATTACCGCT

AAATCTAGGA

GGCAGTCATT

TCAGCTCATT

AAGCCGGCTT

CCACTCAAGA

ATGGGAAATA

AGGATAATAT

ACCAAGAAAG

TCTTGCCTTA

TCAGTTTGGG

TGTTTAACGA

GATTTTCTGA

TTCAAATGAC

CCCCATGCCC

CTCAAGACGC

AATCTTGGGA

CGCCATGTTA

CTAAATTGAT

CAGTGATATT

TGAATCTCTT

ATGGCCCAGG

ACCCTGAAAT

TCATCCATGA

GAGTGCGCAT

AGCAAGTGGA

ATGGCTCTAC

ATCCTAATTC

GCGCTGTTTG

GCAGCCAAAC

TTAGCGCGAT

CAAAAACCTC

AAAAATATTT

CTCAAGCCAA

TTGATTTCAT

TTTTCACTTC

TGTTGAACCA

ACAAGCATTC

TCGTTTCTAG

TTAAAGTGTT

CACGGCTGTA

TGAAACCGGG

AAAACCCAAA

CTACATCTCC

CACCAACTTA

CGCTGAAGA.A

TAACTTGAAC

CGTGATAGAG

CCCACAGCTT

TGCCAGCACG

TTATATCAAT

CCCATACGAA

TAAAAATTTG

AGACGCCGTC

TTCTGATTAC

CGCCAAAAAT

AACGCCGCAA

GCCCACAAGA

CGATGATGGC

ATTGTTTGGC

ATACGGCCAT

GTGCGAAGA.A

TGGGAAAGAA

CTATGATGTG

CATCTATACC

GCAACAACTC

CAACTATTTG

CAGTCAAAGC

ACGGCCCTTT

TAATGATTAT

CAACGAAAAA

CACCAATTAC

CTCTCTTGGG

ATACAAAGGG

CAAATATTCT

CGATGGTGCT

TTTTAATTAC

120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1140 1200 1260 1320 1380 1440 1500 1560 1620 1680 1740 1800 1860 1920 1980 2040 2100 2160 2220 2235 INFORMATION FOR SEQ ID SEQUENCE CHARACTERISTICS: LENGTH: 1590 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) WO 98/24475 PCTIUS97/22104 167 (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc-feature LOCATION .1590 (xi) SEQUENCE DESCRIPTION: SEQ ID

ATGACTTATA

TGCCCCCCAT

GACGCTAAAA

TGGGAAGACG

TGTTATTCTG

TTGATCGCCA

ATATTAACGC

CTCTTGCCCA

CCAGGCGATG

GAAATATTGT

CATGAATACG

CGCATGTGCG

GTGGATGGGA

TCTACCTATG

AATTCCATCT

GTTTGGCAAC

CAAACCAACT

GCGATCAGTC

ACCTCACGGC

TATTTTAATG

GCCAACAACG

TTCATCACCA

ACTTCCTCTC

AACCAATACA

CATTCCAAAT

TCTAGCGATG

GTGTTTTTTA.

TCAATTACAA

ACGAAAACCA

ATTTGACCAA

CCGTCTTAAA.

ATTACCTTAC

AAAATAAAGG

CGCAAGATGT

CAAGAGGAGG

ATGGCACCAA

TTGGCAAAGA

GCCATACTTT

AAGAAAACAA

AAGAAGTGCA

ATGTGTGTTC

ATACCGATTG

AACTCATTGA

ATTTGAACGC

AAAGCCTTTC

CCTTTGGAGC

ATTATCTAGG

AAAAAATCCA

ATTACACTAA

TTGGGGTGTT

AAGGGAGCGG

ATTCTATAGG

GTGCTTATAC

ATTACGGGTG

CCAATTTTCT

AGCAAATTGT

TTTAATGCTG

CGCTCCTTTC

ATGCGTGAAT

AGATGAATAC

TATCTATAGC

GGATTTAGGG

TTTTGGCGCT

ATTGAATAAA

AGGCTATACG

TGGGCCAGAA

AGTGTTTGAC

TCGTTTTAAA

CTCTCAAGTC

TCAAAACGCC

CAGCTTGAAC

ATCTTCTAAA

CCCCCTATTA

GTTGTCTTCT

GCAATTAAGC

CGAAAAGAAC

TGGGGGGTTA

TAATTTAAAT

CATTAGCGTT

CAATTCTATC

GATTTTCTAA

AGCGGTAACG

'GTGGCTAA.AG

AACATGATGG

CAATTCAGCG

CCTTACAACG

AATATAGAAA

TATAGAGTCG

GCAGTGGCTC

TGCCGCCTTT

CGGTGTTTGA

ACAACAACCT

ATGGGCTTGT

ACGGGCAA-AC

CTAATAATAT

TTAGGGTCTC AATATGGTGG

TTAGGGATAT

GTCGCCATCA

CATAACGGGA

GAGCGCTGTC

AACGGGCATG

GATAAGCCCT

CCCGCTGGGC

CTACCGGTGG

ACGCAAGACT

TCTAGCGCCA

GGCGTTAATC

TATGGCATTA

TATGGCGTGG

CCCAAA7AGCA

AGGGGCTTAT.

GTGACCGGTG

CCTTTGGTCC

ACCCTCAATG

TGTCCCCTTT

TGCAATTAAG

ACATGACTTA

AGGGCGGAAG

AAGTGCGAGA

ATACAGCGGG

TTATAGGCGT

ATTTTACTAA

TTGCGACCAC

CTACTTATCG

TTAAAATGGG

TCAAATACAA

GAATGGATGT

ATCTAACCAA

ACAACAGCTA

GGTTGAATTA

AGTTGAAATC

AAGGGGGCAG

TAAACCCCCA

CACCTCTCAA

TTCTAAATCT

GTCAGCGCCA

TGATCCTAAA

AGGCTCAGTG

TTATGTGAAT

CCCGAATGGC

CTTAGACCCT

AGACATCATC

TCAAAGAGTG

GATAGAGCAA

CACCGATGGC

CAGCTATCCT

TACCAGCGCT

TTTGAGCAGC

CATGCTTAGC

CACTTCAAAA

CTATCAAAAA

CTACGCTCAA

GCTGTTTGAT

GAAAGTTTTC

TTATTTGTTG

CCGCTACAAG

TAGGATCGTT

TCATTTTAAA

120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1140 1200 1260 1320 1380 1440 1500 1560 1590 INFORMATION FOR SEQ ID NO:81: SEQUENCE CHARACTERISTICS: LENGTH: 564 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO WO 98/24475 PTU9/20 PCT/US97/22104 168- (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION .564 (xi) SEQUENCE DESCRIPTION: SEQ ID, NO:81:

TTGGGTTGCG

TCGCTTTTTG

GGTCTTAAGG

AAAACGCATG

TTGGGCTTAG

TTAGCCAATG

AACATACAAA

TTGGCGAAAG

GGCTGGGATA

GGGGCTACGC

TATCAATGAC

TGGCGGGGGT

ATAGCAAGAA

GTGAGGTGGG

GGGCGTGTTT

AAATAAAAAT

CCATCATCAA

CTTCTAAGGA

AGAATTGCGG

TTTCATCGGC

TCTAGGTATT

GGTGTGTAAT

GCTCAGCCCC

GTTTTTCGTG

GAAACTCGCT

AGATGGCAAC

GGGCGATGAA

TAGGGAAATG

GTATGGGACT

ATAG

GATGAAGCGG

GAAAAAATAG

AAAAAGCGCT

GTTAAAAAAA

ATTGAAGAAA

ACGGCGTTTG'

ACAATCGCTC

TTAGAACTGC

AAACAACATA

GGAGGGGGTG

CCTTAGAATT

TTTTCTTAGA

GCGCGAATGA

TTGTAGAAAA

GCTTGAACAA

AAATCGCTAT

AC!GCTTTGTT

TAGAAGCGAT

TTTGGCCGGT

TCTAAAAATG

AGATAAAATC

AATTGATCAT

TGGTTGCTCT

ACGCTACCCC

GGCGTCTGTT

TAAGGAATAC

CAATAAGCTA

120 180 240 300 360 420 480 540 564 INFORMATION FOR SEQ ID NO:82: SEQUENCE CHARACTERISTICS: LENGTH: 615 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION .615 (xi) SEQUENCE DESCRIPTION: SEQ ID N0:82:

ATGACTCTAG

GGGGTGGTGT

AAGAAGCTCA

GTGGGGTTTT

TGTTTGAAAC

AA.AATAGATG

ATCAAGGGCG

AAGGATAGGG

TGCGGGTATG

CATCGGCATA

GTATTGATGA

GTAATGAAAA

GCCCCAAAAA

TCGTGGTTAA

TCGCTATTGA

GCAACACGGC

ATGAAACAAT

AAATGTTAGA

GGACTAAACA

GCTTCACGCT

AGCGGGGAGG

AATAGCCTTA

GCGCTTTTTC

AAAAAGCGCG

AGAAATTGTA

GTTTGGCTTG

CGCTCAAATC

ACTGCACGCT

ACATATAGAA

TAAAAACCGC

GGGTGTTTGG

GAATTTCTAA.

TTAGAAGATA

AATGAAATTG

GAAAATGGTT

AACAAACGCT

GCTATGGCGT

TTGTTTAAGG

GCGATCAATA

ATCTTAAATC

CCGGTTCGCT

AAATGGGTCT

AAATCAAAAC

ATCATTTGGG

GCTCTTTAGC

ACCCCAACAT

CTGTTTTGGC

AATACGGCTG

AGCTAGGGGC

CCAAACTCTT

TTTTGTGGCG

TAAGGATAGC

GCATGGTGAG

CTTAGGGGCG

CAATGAAATA

ACAAACCATC

GAAAGCTTCT

GGATAAGAAT

TACGCCTTTT

AGAGGTGGAA

WO 98/24475 PCT/US97/22104 -169- CAACGCCTTG TTTAA 615 INFORMATION FOR SEQ ID NO:83: SEQUENCE CHARACTERISTICS: LENGTH: 579 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...579 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:83:

ATGAATGCAT

ACAGTGCATG

CTTTTTGATA

AGGAACGATT

GCTGAAGAAA

TTACTCACTA

AGCCATTTAT

GTGGATACCA

TGAAAAAATT

CTCAGCATTT

AAAAGAACCC

TTTATTCCAA

TCGCTCTTTT

AAATGTGCAA

TCGGGTTTGT

CCAACCATCG

AAGTTTTTGC

AAAGGACACG

GCCCAATCAA

TTACATCCCC

AAGGGCCAGA

TCGCATTGTT

TGATTTTTTA

TGTGTATGTC

GCCTTGTTAT

ATTAACTATC

TATGTCGGAT

TATGATGACA

ATGAACGCTT

AAAGCGCTTC

ACGTCTAAAT

ATGGTGCAAT

ATCGACCTTT

CACCTCTAA

CCCTAGGCCT

CTGATTGGCT

CGGCTTCAAT

AATTGCCCCC

ACAGCACTTT

AAGTTAAAAA

CCATTTTGGC

TCCCTTTCAT

CTTTAGCGAG

CTTCGCTCAA

TAAAATCAAT

TTCTGGTAAA

TGAAAAGAAC

AGAAAGCGCT

TAATGTTATC

TAAAAGGTTC

TCAGCCTGAA

CGCTACCAAT

120 180 240 300 360 420 480 540 579 GACTTAATCG CTTACTTTAA AGCCAAACGC.

CTCAGCGCCA TTTTAAACAA GGCGTTGTTC INFORMATION FOR SEQ ID NO:84: SEQUENCE CHARACTERISTICS: LENGTH: 261 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: WO 98/24475 PCT/US97/22104 -170- NAME/KEY: misc feature LOCATION 1...261 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:84:

ATGAATGCAT

ACAGTGCATG

CTTTTTGATA

AGGAACGATT

CTGAAGAAAT

TGAAAAAATT AAGTTTTTGC GCCTTGTTAT CTCAGCATTT AAAGGACACG ATTAACTATC AAAAGAACCC GCCCAATCAA TATGTCGGAT TTTATTCCAA TTACATCCCC TATGATGACA CGCTCTTTTA A CCCTAGGCCT CTTCGCTCAA CTGATTGGCT TAAAATCAAT CGGCTTCAAT TTCTGGTAAA AATTGCCCCC TGAAAGAACG 120 180 240 261 INFORMATION FOR SEQ ID SEQUENCE CHARACTERISTICS: LENGTH: 228 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: miscfeature LOCATION 1...228 (xi) SEQUENCE DESCRIPTION: SEQ ID

TTGAAAATTT

GCGCTTAAAA

ATTGAAACAA

GAATTGAACG

TAACCCTTTT TTTGATAGGT TTAAACGCAT TGTTCGCCCT AGATTTGAAC CAGAAATCAA AGAAACCTAT CTCAAAGAAT ACAAAGACTT AAAATTGGAA TTAATTTAGA AATCCCAGAG CGTTTTTCTC ACGCTTCCAT TTTAAGCTAT CTTCTAACAA GCTTAAAAAA GATGGGTCGT GTTTTTAA 120 180 228 INFORMATION FOR SEQ ID NO:86: SEQUENCE CHARACTERISTICS: LENGTH: 636 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOG.: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: WO 98124475 PTU9/20 PCTIUS97/22104 171 ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc-feature LOCATION .636 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:86: ATGTTTTCA.A TAATTCTGGG GGGGGGGGGG GGTAATACCC IU CACTTCAAAT

TTAACGCAAG

CAAACTACAG

CTTTTGCAAA

AAAATCACAC

ACAACGCTTT

AAAACTTTTA

CTTGATGGTA

ATTCAAGGCG

CAAGAAACGC

TAGGGGATTT

GACAAGATTA

GATTTGTCAA

TGGATTTTTT

CAAAAACTGA

TAAACGCCTT

GGGAGCAAAA

TTGATTTTGA

TGGTTCAATA

GTTTGAAATT

CGATTATATT

TGCAGAAAAT

CTATCGTAAA

AATTAAAAAT

AAAACGCCCT

AATCCAACTA

TTTCATGCAC

CTGCGACGCT

GAAAAAACCT

ACAAGAACTT

TTAAACCCAC

AAGTCATGGT

AAAATTAATT

TTATTGAGTG

CCCCTAAAAC

ACCCTAATCA

AAAATACAGG

TTTTGA

CATGCGGCTT

TAAGCTTTAA

CGCAAAATCA

CATTTACTTG

ATGCGGGACA

CACGCATAGC

TATTAGTTAG

CCACCGCTAA

ACGCCCTGAT

CTACAAAAGA

GACATGGCAA

TAAAGACGCT

AGGCGTTTTG

GAGTTTAGGG

ATTCATGCGA

CCACTATTTC

GGATATTGAT

AACTCAAAGC

GAAGCAAACC

AGTTATCAGC

120 180 240 300 360 420 480 540 600 636 CTATTCAAAA AGACTCGTTA INFORMATION FOR SEQ ID NO:87: SEQUENCE CHARACTERISTICS: LENGTH: 1221 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pyvloni (ix) FEATURE: NAME/KEY: misc feature LOCATION 1. .1221 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:87:

GTGATTGGCC

GATTTGTTTG

GGCGAATTTG

AAAGCAAAAG

CGCAGTTTTG

GAAATCAACC

TTCGGCTATG

CTAAAACCCA

TTCATAGCCG

GGGCTAGAAA

TCTGGGGGGG

CCCTTAGCAG CCAACTCAAC AAGCGAGTAA CGGCGATTTT

TCATCACCGC

TTTTTGAAAG

CTTATAAAAT

ATAAAATCGG

AAAACATGTG

CCGCTAACAC

AACTTGAGCA

ACACCACCCT

GGGGGGGTAA

AGGGCTTAGC

CCATACCATT

GGTAACACAT

CTTGTTTTTA

TTCATGGGCA

TCAAACCCTT

GTGTCGGCTC

TTCTAACGAT

TACCCCATGC

GCTATTAAGT

GACATTCAAA

AATAATGGCG

ACTATTGACA

GCTAGGGTAT

TCCACGCTAT

AAAATTAAAA

GAGGGTATTG

GCCGAACTTC

GAAGAAAATG

GGCTTGACAT

GGGGCGAGTT

AACGCCACAT

TTTTAGGGCA

TGTTTGGTTG

TTTCTCTCAA

TTTTTGGTTA

ACGATAAAGT

ATTTTGATTT

AGGCTTATTT

CCCTTAATGT

GGCAACACTT

CAAATTAGGG

CAATCATAAG

AAGCGATATA

CGCGTTTTAT

ACCTAAATTT

CCATAAAAAA

CATTCTACCC

CATGGAAAAA

AAAAGCTACA

TTTCAATAAT

CAAATTAGGG

120 180 240 300 360 420 480 540 600 660 WO 98/24475 PTU9/20 PCT[US97/22104 172

GATTTGTTTG

GATTACGATT

GTCAATGCAG

TTTTTCTATC

ACTGAAATTA

GCCTTAAAAC

CAAAAAATCC

TTTGATTTCA

CAATACTGCG

CAAAAAGACT

AAATTGAAAA

ATATTACAAG

AAAATTTAAA

GTAAAAAGTC

AAAATAAAAT

GCCCTTTATT

AACTACCCCT

TGCACACCCT

ACGCTAAAAT

CGTTATTTTG

AACCTTAAGC

AAC!TTCGCAA

CCCACCATTT

ATGGTATGCG

TAATTCACGC

GAGTGTATTA

AAAACCCACC

AATCAACGCC

ACAGGCTACA

TTTAATAAAG

AATCAAGGCG

ACTTGGAGTT

GGACAATTCA

ATAGCCCACT

GTTAGGGATA

GCTAAAACTC

CTGATGAAGC

AAAGAAGTTA

ACGCTTTAAC

TTTTGCAAAC

TAGGGCTTTT

TGCGAAAAAT

ATTTCACAAC

TTGATAAAAC

AAAGCCTTGA

AAACCATTCA

TCAGCCAAGA

GCAAGGACAA

TACAGGATTT

GCAAATGGAT

CACACCAAAA

GCTTTTAAAC

TTTTAGGGAG

TGGTATTGAT

AGGCGTGGTT

AACGCCTATT

720 780 840 900 960 1020 1080 1140 1200 1221 INFORMATION FOR SEQ ID NO:88: Wi SEQUENCE CHARACTERISTICS: LENGTH: 828 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genornic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc-feature LOCATION .828 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:88: ATGAGTAAGA GTTTATACCA AACTTTAAAC.'GTGAGCGAAA ACGCCAGCCA

AAAAAATCCT

GCCGAAGAGA

CGCCGCCAAT

GCCAGAAGCC

GGAGGCTTTT

AATTTCGCCC

CTTTTAGGCA

ATCGGCGTGG

GGTAGGGGCG

AAAGACGATA

ATTGAAATCG

ATGCAAAAAT

GATTGTATTG

ACCGCCGTTT

AATTCAAAGA

ACGATCAATT

GTGGTCCTAG

CGCAAAGATT

CTGAAAATTT

ATAAAAAACA

AAGAGGGCGA

ATTTGCTCTT

TTATCCAAAT

CTACTTGGCA

TCCGCATCAA

CAAGCTCGTT

AGCCAGGCAA

AATCAACGCC

TGGCGACAAC

TGAAGATTTA

TTCTCAAAAT

AGATGTAACC

AGTGAGCGTC

AAAGATTAGG

ACAGATCCAT

CTTTGATTTA

TAAAACCTTA

AGACAAAGGG

TGATCTGCTA

TACCACCCGG

GCTTATGAAA

ATGTTTGGCG

GATGATATTT

TCGCAAGGCT

GCTATTTTAA

AATAATGAGA

GTTCGCAACA

ATTGAAGAAG

CCCTTAAAAA

ACCCTAACCA

ATCAAAAGCA

AAATTGAAAC

ATTTGAATAA

TTTTGAGCGA

GGCAGAATTT

TAAGCTCTAT

TTTCTGGCTT

ATGTCTCTGT

CTTTTAG CCT

AAGGGAAAAT

ATGAAATGTA

CGGCTCTTTT

TTCCCCCTAA

GAAAAACTTC

GCTTCTAA

AGATGAAATC

AACCAAAGAA

TGAAGAAAAA

CAGCGATTTT

TTTTGGGAAA

TAATTTTTCC

TTTAGACACC

TAAAATCCCT

GGGGCGAACG

TAGGCGCGAA

TGGAGGGAAA

CACCAAA.(-,

GCATGTGGGG

120 180 240 300 360 420 480 540 600 660 720 780 828 INFORMATION FOR SEQ ID NO:89: Wi SEQUENCE CHARACTERISTICS: LENGTH: 837 base pairs TYPE: nucleic acid WO 98/24475 PTU9/20 PCT/US97/22104 -173- STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc-feature LOCATION .837 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:89:

ATGAGTAAGA

AAAAAATCCT

GCCGAAGAGA

CGCCGCCAAT

GCCAGAAGCC

GGAGGCTTTT

AATTTCGCCC

CTTTTAGGCA

ATCGGCGTGG

GGTAGGGGCG

AAAGACGATA

ATTGAAATCG

ATGCAAAAAT

GATTGTATTG

GTTTATACCA

-ACCGCCGTTT

AATTCAAAGA

ACGATCAATT

GTGGTCCTAG

CGCAAAGATT

CTGAAAATTT

ATAAAAAACA

AAGAGGGCGA

ATTTGCTCTT

TTATCCAAAT

CTACTTGGCA

TCCGCATCAA

CAAGCTCGTT

AACTTTAAAC

AGCCAGGCAA

AATCAACGCC

TGGCGACAAC

TGAAGATTTA

TTCTCAAAAT

AGATGTAACC

AGTGAGCGTC

AAAGATTAGG

ACAGATCCAT

CTTTGATTTA

TAAAACCTTA

AGACAAAGGG

TGATCTGCCT

GTGAGCGAAA

TACCACCCGG

GCTTATGAAA

ATGTTTGGCG

GATGATATTT

TCGCAAGGCT

GCTATTTTAA

AATAATGAGA

GTTCGCAACA

ATTGAAGAAG

CCCTTAAAAA

ACCCTAACCA

ATCAAAAGCA

AAAATTGAAA

ACGCCAGCCA

ATTTGAATAA

TTTTGAGCGA

GGCAGAATTT

TAAGCTCTAT

TTTCTGGCTT

ATGTCTCTGT

CTTTTAGCCT

AAGGGAAAAT

ATGAAATGTA

CGGCTCTTTT

TTCCCCCTAA

GAAAAACTTC

CGCTTCTAAT

AGATGAAATC

AACCAAAGAA

TGAAGAAAAA

CAGCGATTTT

TTTTGGGAAA

TAATTTTTCC

TTTAGACACC

TAAAATCCCT

GGGGCGAACG

TAGGCGCGAA

TGGAGGGAAA

CACCAAAGCC

GCATGTGGGG

GAGTTGA

120 180 240 300 360 420 480 540 600 660 720 780 837 INFORMATION FOR SEQ ID SEQUENCE CHARACTERISTICS: LENGTH: 699 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION .699 WO 98/24475 PTU9I2O PCTIUS97/22104 -174- (xi) SEQUENCE DESCRIPTION: SEQ ID

GTGGTTCAAA

TTCCTTTTTA

AAAAAAGATG

CTTTTTGCTA

AATTCCCCCC

GAGTATGTTT

AATGTGGATT

0 TCTAAAGACC

TACCCTAACA

CAAAATGAGC

GTGAAACGCT

AATTTAATTT

TCACAATGGC

AATACAACAA

ATTTAGAAAC

TTGTCCCAGA

TAG CGTCTTT

ATTTGACCTT

AGGAATTTAT

GCCGTTACCG

TCAATCGCGC

ATTTAGAAAG

TTATAAGACA

GGTGATTGTG

ACCGGCGATC

AGCGGACAAT

AGCTATGCTA

TTACTTTGAT

TTTGAAACTG

CTCTAATTCT

CCCCTATGTA

GATCGCGAAT

GATAGATGAG

GTTAATTTTT

GGTGGCATGC

ATAGGCACTG

TTTTGGTATC

TACTATTCTT

GCTTTAGGGC

GAATACATCA

CAATCGCATT

ATTGTGAGTT

GAATACATGC

GTCTATAAAA

ACTTTAGAAA

GATTGGTAG

GTTTAAAACA

GTTGTGCGAA

AAGGGATTTT

CCTTACAGAG

AAGCGCACAT

AGCGCTTTGG

ATTACGCTTT

TAGGCGAATT

AAATCAAATT

AACGCCACAA

AAGAGACTAA

TTTTAAGACA

TAAAAAGAAA

GAGAGAAATT

CGAACACATC

GAAAAAGAAA

GACGAAGGAC

CAAAAACCAT

TATAGAAAAA

CATTTTAGGG

GCCCGAGGGC

ACCCAAACCA

120 180 240 300 360 420 480 540 600 660 699 TCGCACATGC CTTGGTATGT INFORMATION FOR SEQ ID NO:91: SEQUENCE CHARACTERISTICS: LENGTH: 345 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION .345 (xi) SEQUENCE DESCRIPTION: SEQ ID N'O:91:

ATGCGTTTTT

GGGTTTTTAA

GAAATTGATA

GAAAATTTTG

ATCCGCTGTT

GTGAAAAATG

TGAATAACAA

AAACGCTGGG

TTATCGCTTT

ATCCCATTTA

ATTTGTCTCA

GTAAATTTGA

ACATAGAGAA

TTTTGAAATG

GAAAAAAGGG

TGCGATCACG

AAAAGATCCC

GCTTTTAGAA

AAGGGCTTAA

ATAGAGAGGA

GTTTTGCATT

CCGAGCAAAT

AATAGCGATT

AATATCACTT

AGGCTGAAGA

ACTTTTTTTC

TCATTGAAGT

TAAAA~AAGAT

TTTGCATTGA

TTTAG

AGAAGCTTGC

ACAATTTGGT

CAAAAGCGGG

GATTAAAACG

CGCTCTTATT

INFORMATIC_:.'OR SEQ ID NO:92: SEQUENCE CHARACTERISTICS: LENGTH: 306 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) WO 98/24475 PTU9/20 PCT/US97/22104 175- (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION .306 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:92:

ATGGGCAGCA

GCGAGTGAAA

TCGGATATGA

AAGAATATTT

AAAAAAAGCC

TTTTAA

TTGGGGCTAT

AATTAGTCCC

TTTTCCAATT

TGGAATTGTA

ATGTGCATGG

GACTAAAGGG

AGAAGGCATT

AGTAGGGGGC

TCAAAACGCT

CGTGGATATT

AGCTCTGATA GGTATTTTCA GAGGGGCGTG TGCCTTATCG GTGCGTTCTT CTATGGGGTA GAATTTGTAG AAATCAC TAG ACTAAAGALAG CCCCTAATAT

AGAGGGCGTG

TGGTAAGGTT

TCAGGGGGCG

CGCGGGGTTA

TATGGGTGAA

120 180 240 300 306 INFORMATION FOR SEQ ID NO:93: SEQUENCE CHARACTERISTICS: LENGTH: 1446 base pairs TYPE: nucleic acid STRAflDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genoinic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc-feature LOCATION .1446 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:93:

ATGAGAATTT

AGCGTTTTAC

ATCCCTTTTA.

GCGCGCCTTG

GAAATCACTA

GCGCACAGGA

CCTGTGGTAG

GAAACCGATT

CATGTGGGCA.

TTGCCCATTG

TACAAAGGGC

CTAAAGATGT

TTAGTGCGGC

GGGGTATTGG

AAGTTAAAAA

CGCTAGCGGA

ATGATAAGGG

TGAGTAAAAA

TTAGCTTAGA

TGGATAAAGA

TTTGACTTTT

GAGCTTAAAG

TATGGATACG

CATCGTGCAT

AAGCGAGAGC

CGCTAAAGTC

GTTGTTGATT

AGTGGGCGAT

TGAAGCGAGC

TAATGTTTTA

GAAGACGTGT

TCTCGCCTAA

GTTACAGAGC

AAAAACATGG

GGGGTGATTA

ATAACGGATA

GGGATTTTAA

GTGATGACTA

GATTTGATGC

AAAGGCTTGA

TGATGGTGCC

CCAAAAACAT

ATAAAACCGC

ATATTCAAAC

ATGATCCTAT

ATTATAAGAT

CCAACAGAGA

AAATGCCTTT

ACAAGCATAA

TCACGATCAA

TAGAAAATCC

TGGTTTGAAT

TATCGCTATG

GCAAGTCAAA

TTTTATCCAT

TTCAGGCGTG

CGTGCGTTTT

AGTTACCGCT

GATTGAAAAA.

AGACATTCAA

WO 98/24475 PTU9/20 PCTIUS97/22104 -176-

AAACGCATTG

GCTATTGGAG

TTGGTGTTAG

AAAAAAAGCT

GATTTGATTA

ACCACTAGGA

GAAGTGGCGT

GATGTGGCTA

GGCACAGAAG

AGGGGCATGG

GGCGTGGCGA

AAGGTTTCGG

GGGGCGAAGA

GGGTTAAAAG

GGGTGA

AATACCCTGA

TGGGGCAGTT

ACAGCGCGCA

TGGTAGTGGA

GCGCGGGAGC

TTGTGGCCGG

CTAAATTTGA

AGGCTCTAGC

AATCTCCAGG

GCAGCATTGG

GTGAAAAATT

ATATGATTTT

ATATTTTGGA

AAAGCCATGT

GGCCAATAAA GATGATTTTG GGAGGTTGAG GGATAGGGCT GAAATGTTAG TTAAAGCGGG

TGGGCATTCA

TGTGATTGTG

GGACGCTGTT

GGTGGGAATG

TATTCCTGTG

TTTAGGAGCA

GGATTTTATG

GGCTATGACT

AGTCCCAGAA

CCAATTAGTA

ATTGTATCAA

GCATGGCGTG

GCCAATATTT

GGGAATGTGG

AAAGTGGGTA

CCCCAAGTGA

ATTGCCGATG

TCAAGCGTGA

ATTTACCAAG

AAAGGGAGCT

GGCATTGAGG

GGGGGCGTGC

AACGCTGAAT

GATATTACTA

TACACACTTT

TTACTAAAGA

TTGGGCCAGG

GCGCAATTGA

GAGGGATCCG

TGATAGGCTC

GGAGGCAATA

CTGATAGGTA

GGCGTGTGCC

GTTCTTCTAT

TTGTAGAAAT

AAGAAGCCCC

AGTGGGGGCG

GGTGGATGCG

AGAAGAGATT

AGCCACAAGC

AAGCATTTGC

TAATTGCGTG

CTATTCAGGC

TTTACTCGCT

TAAAAGCTAT

TTTTCAAGAG

TTATCGTGGT

GGGGTATCAG

CACTAGCGCG

TAATTATTAT

660 720 780 840 900 960 1020 1080' 1140 1200 1260 1320 1380 1440 1446 INFORMATION FOR SEQ ID NO:94: SEQUENCE CHARACTERISTICS: LENGTH: 615 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc Ifeature LOCATION .615 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:94: 4U ATGCAAGGGT

TTAACCAAAA

AATGTGGGTC

AGGAATATTT

CAACGCTTTT

TATTTTGACA

ATTTTAGAAA

TGTTTTTTAT

GCGCACCCCT

CGCACTCAAA

TTCTTTTACA

ACCAGCTCAA

GTAAAATTGA

TGCATTTAGG

GCGCTCTTTT

CTTTAGATGA

TGTATGCAGT

GCGATGCAAA

CTTGCTTGAA

GCACGATTGA

AACACAAAGC

AACCCTCTAT

TTTTGAAGAA

CTATATTTGG

GTTCAAGCAT

TGGGGCTAGC

CCTTTTGAAT

ATTAGAGCGT

AGCTAAAAGC

TCTAGAAACA

ATAAGAGATG

CGTTTCTATG

GAAAACGATG

GAAAGAGAAA

TTAGAGGGCG

AAACTCTCCA

TTTGAAGGGC

TCTGTCGCTT

TTGGATTTAG

GAAGA.AGTGG

AAGATTTGAT CGTGCACGTT GCAAACGCCA CAGCGTGCTG

ATAAATTTTT

TGGAGCGCTT

TGCATTCTTT

AACAGCACCC

GCTTGCAAAG

TAGCGCAAGG

AAAAAATCCA

AAGAATTATG

ACCCAAGTTA

GTTTTTTTGG

AGATAGCATC

CTT OAGAGTG T .CAATTCT

GTTTATTTTA

AGCTTTTTTC

GCGCACGCTG

120 180 240 300 360 420 480 540 600 50 AATTTAGGGT TTTGA INFORMATION FOR SEQ ID SEQUENCE CHARACTERISTICS: WO 98/24475 PCT[US97/22104 -177- LENGTH: 249 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...249 (xi) SEQUENCE DESCRIPTION: SEQ ID ATGGGCGTCG GACGGGTCGG CAATATGGCA CTGTTGGCGT GTGCAGGTCC GATGGGCATC GGCGCTATTG CTATCGCCAT TAACGGCGGC AGACAACGGT CGCGGATGTT GGTGGTCGAT 120 ATAGACGACA AACGTCTGGA GCAGGTACAG AAGATGCTGC CGGGGAATTG GCGGCCAGTA 180 ACGGCATTGA GCTGGTGTCT GTGCATACCA AAGCGAGGAG CGATCCGTGC CAGATGCTGC 240 GAGCGCTGA 249 INFORMATION FOR SEQ ID NO:96: SEQUENCE CHARACTERISTICS: LENGTH: 204 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: miscfeature LOCATION 1...204 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:96: TTGTCCGGTA CAGCCGTGAG TTGCCGGTGC ACATGCCGCA TACAGTTGGT ATTGGTGCGC ACCAGCATCC CGGTTGTTAT CGGGTGCTCA TGCCCATTCC TTTCCAGTAT TGGGTTCACA 120 ACGGGAACCC ACCAATCACC CGTTAAACGC TGCGGGGTTA ACGCCGGAAA AACACCGTCA 180 AAAAAACATT TGCATTTAAA CTAA 204 WO 98/24475 PCT/US97/22104 -178- INFORMATION FOR SEQ ID NO:97: SEQUENCE CHARACTERISTICS: LENGTH: 345 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: miscfeature LOCATION 1...345 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:97:

GTGTGGCTGG

ATCGCCCTGG

CCGGCGGCCT

GCACCGCCAC

CGGCGCTGTT

CCGGTCGCCT

CGGCGCTGGG

CCAAGGTCGG

GCTGGCGGCG

GGTGTCCTTC

CGTCTACAGC

GCTGGACACC

CTTCCTGATC

CGGTTCGTCG

GTCTGCTACC

GAAGGTCAGC

CTGGCGTACT

GTCGGACGCT

ACCGCGGTGG

ACGCCCTCAG

TGGCGGTCGG

GTGGTGCCGC

TCCTCCTCGC

TCCTCGCCCC

GGCTGCCGGT

CCATCCGATC

CCCGCTGTTC

TGCTCGGCGA

CCTGGCCATC

GCTGA

GATCACCGTG

GGCAGGTATG

GCCATTCCGC

AGAAGCGGCA

TCCCTCTACC

INFORMATION FOR SEQ ID NO:98: SEQUENCE CHARACTERISTICS: LENGTH: 228 amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) TEATURE: NAME/KEY: miscfeature LOCATION 1...228 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:98: Met Arg Phe Lys Gly Ser Arg Val Glu Ala Phe Leu Gly Ala Leu Glu 1 5 10 Phe Gln Glu Asn Glu Tyr Glu Glu Phe Lys Glu Leu Tyr Glu Ser Leu 25 WO 98/24475 PCT/US97/22104 -179- Lys Thr Lys Gin Lys Pro His Thr Leu Phe Ile Ser Cys Val Asp Ser 40 Arg Val Val Pro Asn Leu Ile Thr Gly Thr Gin Pro Gly Glu Leu Tyr 55 Val Ile Arg Asn Met Gly Asn Val Ile Pro Pro Lys Thr Ser Tyr Lys 70 75 Glu Ser Leu Ser Thr Ile Ala Ser Val Glu Tyr Ala Ile Ala His Val 90 Gly Val Gin Asn Leu Ile Ile Cys Gly His Ser Asp Cys Gly Ala Cys 100 105 110 Gly Ser Ile His Leu Ile His Asp Glu Thr Thr Lys Ala Lys Thr Pro 115 120 125 Tyr Ile Ala Asn Trp Ile Gin Phe Leu Glu Pro Ile Lys Glu Glu.Leu 130 135 140 Lys Asn His Pro Gln Phe Ser Asn His Phe Ala Lys Arg Ser Trp Leu 145 150 155 160 Thr Glu Arg Leu Asn Ala Arg Leu Gin Leu Asn Asn Leu Leu Ser Tyr 165 170 175 Asp Phe Ile Gin Glu Arg Val Ile Asn Asn Glu Leu Lys Ile Phe Gly 180 185 190 Trp His Tyr Ile Ile Glu Thr Gly Arg Ile Tyr Asn Tyr Asn Phe Glu 195 200 205 Ser His Phe Phe Glu Pro Ile Glu Glu Thr Ile Lys Gin Arg Ile Ser 210 215 220 His Glu Asn Phe 225 INFORMATION FOR SEQ ID NO:99: SEQUENCE CHARACTERISTICS: LENGTH: 221 amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...221 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:99: Val Glu Ala Phe Leu Gly Ala Leu Glu Phe Gin Glu Asn Glu Tyr Glu 1 5 10 Glu Phe Lys Glu Leu Tyr Glu Ser Leu Lys Thr Lys Gin Lys Pro His 25 Thr Leu Phe Ile Ser Cys Val Asp Ser.Arg Val Val Pro Asn Leu Ile 40 Thr Gly Thr Gin Pro Gly Glu Leu Tyr Val Ile Arg Asn Met Gly Asn WO 98/24475 PCTIUS97/22104 -180- 55 Val Ile Pro Pro Lys Thr Ser Tyr Lys Glu Ser Leu Ser Thr Ile Ala 70 75 Ser Val Glu Tyr Ala Ile Ala His Val Gly Val Gin Asn Leu Ile Ile 85 90 Cys Gly His Ser Asp Cys Gly Ala Cys Gly Ser Ile His Leu Ile His 100 105 110 Asp Glu Thr Thr Lys Ala Lys Thr Pro Tyr Ile Ala Asn Trp Ile Gin 115 120 125 Phe Leu Glu Pro Ile Lys Glu Glu Leu Lys Asn His Pro Gin Phe Ser 130 135 140 Asn His Phe Ala Lys Arg Ser Trp Leu Thr Glu Arg Leu Asn Ala Arg 145 150 155 160 Leu Gin Leu Asn Asn Leu Leu Ser Tyr Asp Phe Ile Gin Glu Arg Val 165 170 175 Ile Asn Asn Glu Leu Lys Ile Phe Gly Trp His Tyr Ile Ile Glu Thr 180 185 190 Gly Arg Ile Tyr Asn Tyr Asn Phe Glu Ser His Phe Phe Glu Pro Ile 195 200 205 Glu Glu Thr Ile Lys Gin Arg Ile Ser His Glu Asn Phe 210 215 220 INFORMATION FOR SEQ ID NO:100: SEQUENCE CHARACTERISTICS: LENGTH: 335 amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc_feature LOCATION 1...335 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:100: Met Leu Val Thr Arg Phe Lys Lys Ala Phe Ile Ser Tyr Ser Leu Gly 1 5 10 Val Leu Val Val Ser Leu Leu Leu Asn Val Cys Asn Ala Ser Ala Gin 25 Glu Val Lys Val Lys Asp Tyr Phe Gly Glu Gin Thr Ile Lys Leu Pro 40 Val Ser Lys Ile Ala Tyr Ile Gly Ser Tyr Val Glu Val Pro Ala Met 50 55 Leu Asn Val Trp Asp Arg Val Val Gly Val Ser Asp Tyr Ala Phe Lys 70 75 Asp Asp Ile Val Lys Ala Thr Leu Lys Gly Glu Asp Leu Lys Arg Val 90 WO 98/24475 PCT/US97/22104 181 Lys His Met Ser Thr Asp His Thr Ala Ala Leu Asn Val Glu Leu Leu 100 105 110 Lys Lys Leu Ser Pro Asp Leu Val Val Thr Phe Val Gly Asn Pro Lys 115 120 125 Ala Val Glu His Ala Lys Lys Phe Gly Ile Ser Phe Leu Ser Phe Gin 130 135 140 Glu Thr Thr Ile Ala Glu Ala Met Gln Ala Met Gin Ala Gin Ala Thr 145 150 155 160 Val Leu Glu Ile Asp Ala Ser Lys Lys Phe Ala Lys Met Gin Glu Thr 165 170 175 Leu Asp Phe Ile Ala Glu Arg Leu Lys Gly Val Lys Lys Lys Lys Gly 180 185 190 Val Glu Leu Phe His Lys Ala Asn Lys Ile Ser Gly His Gin Ala Ile 195 200 205 Ser Ser Asp Ile Leu Glu Lys Gly Gly Ile Asp Asn Phe Gly Leu Lys 210 215 220 Tyr Val Lys Phe Gly Arg Ala Asp Ile Ser Val Glu Lys Ile Val Lys 225 230 235 240 Glu Asn Pro Glu Ile Ile Phe Ile Trp Trp Val Ser Pro Leu Thr Pro 245 250 255 Glu Asp Val Leu Asn Asn Pro Lys Phe Ser Thr Ile Lys Ala Ile Lys 260 265 270 Asn Lys Gin Val Tyr Lys Leu Pro Thr Met Asp Ile Gly Gly Pro Arg 275 280 285 Ala Pro Leu Ile Ser Leu Phe Ile Ala Leu Lys Ala His Pro Glu Ala 290 295 300 Phe Lys Gly Val Asp Ile Asn Ala Ile Val Lys Asp Tyr Tyr Lys Val 305 310 315 320 Val Phe Asp Leu Asn Asp Ala Glu Ile Glu Pro Phe Leu Trp His 325 330 335 INFORMATION FOR SEQ ID NO:101: SEQUENCE CHARACTERISTICS: LENGTH: 274 amino'acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...274 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:101: Met Leu Val Thr Arg Phe Lys Lys Ala Phe Ile Ser Tyr Ser Leu Gly 1 5 10 Val Leu Val Val Ser Leu Leu Leu Asn Val Cys Asn Ala Ser Ala Gin WO 98/24475 PCTI~S97/22104 -182- 25 Glu Val Lys Val Lys Asp Tyr Phe Gly Glu Gin Thr Ile Lys Leu Pro 40 Val Ser Lys Ile Ala Tyr Ile Gly Ser Tyr Val Glu Val Pro Ala Met 50 55 Leu Asn Val Trp Asp Arg Val Val Gly Val Ser Asp Tyr Ala Phe Lys 70 75 Asp Asp Ile Val Lys Ala Thr Leu Lys Gly Glu Asp Leu Lys Arg Val 90 Lys His Met Ser Thr Asp His Thr Ala Ala Leu Asn Val Glu Leu Leu 100 105 110 Lys Lys Leu Ser Pro Asp Leu Val Val Thr Phe Val Gly Asn Pro Lys 115 120 125 Ala Val Glu His Ala Lys Lys Phe Gly Ile Ser Phe Leu Ser Phe Gin 130 135 140 Glu Thr Thr Ile Ala Glu Ala Met Gin Ala Met Gin Ala Gin Ala Thr 145 150 155 160 Val Leu Glu Ile Asp Ala Ser Lys Lys Phe Ala Lys Met Gin Glu Thr 165 170 175 Leu Asp Phe Ile Ala Asp Arg Leu Lys Gly Val Lys Lys Lys Lys Gly 180 185 190 Val Glu Leu Phe His Lys Ala Asn Lys Ile Ser Gly His Gin Ala Ile 195 200 205 Asn Ser Asp Ile Leu Gin Gin Gly Gly Ile Asp Asn Phe Gly Leu Lys 210 215 220 Tyr Val Lys Phe Gly Arg Ala Asp Ile Ser Val Glu Lys Ile Val Lys 225 230 235 240 Glu Asn Pro Glu Ile Ile Phe Ile Arg Trp Val Thr Pro Leu Thr Pro 245 250 255 Asp Tyr Val Leu Asn Asn Pro Lys Phe Ser Thr Ile Asn Ala Ile Lys 260 265 270 Asn Ile INFORMATION FOR SEQ ID NO:102: SEQUENCE CHARACTERISTICS: LENGTH: 428 amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...428 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:102: WO 98/24475 PCTfUS97/22104 -183 Met Lys Lys Lys Phe Leu Ser Leu Thr Leu Gly Ser Leu Leu Val Ser 1 5 10 Ala Leu Ser Ala Glu Asp Asn Gly Phe Phe Val Ser Ala Gly Tyr Gin 25 Ile Gly Glu Ser Ala Gin Met Val Lys Asn Thr Lys Gly Ile Gin Asp 40 Leu Ser Asp Ser Tyr Glu Arg Leu Asn Asn Leu Leu Thr Asn Tyr Ser 55 Val Leu Asn Ala Leu Ile Arg Gin Ser Ala Asp Pro Asn Ala Ile Asn 65 70 75 Asn Ala Arg Gly Asn Leu Asn Ala Ser Ala Lys Asn Leu Ile Asn Asp 90 Lys Lys Asn Ser Pro Ala Tyr Gin Ala Val Leu Leu Ala Leu Asn Ala 100 105 110 Ala Ala Gly Leu Trp Gin Val Met Ser Tyr Ala Ile Ser Pro Cys Gly 115 120 125 Pro Gly Lys Asp Thr Ser Lys Asn Gly Gly Val Gin Thr Phe His Asn 130 135 140 Thr Pro Ser Asn Gin Trp Gly Gly Thr Thr Ile Thr Cys Gly Thr Thr 145 150 155 160 Gly Tyr Glu Pro Gly Pro Tyr Ser Ile Leu Ser Thr Glu Asn Tyr Ala 165 170 175 Lys Ile Asn Lys Ala Tyr Gin Ile Ile Gin Lys Ala Phe Gly Ser Ser 180 185 190 Gly Lys Asp Ile Pro Ala Leu Ser Asp Thr Asn Thr Glu Leu Lys Phe 195 200 205 Thr Ile Asn Lys Asn Asn Gly Asn Thr Asn Thr Asn Asn Asn Gly Glu 210 215 220 Glu Ile Val Thr Lys Asn Asn Ala Gin Val Leu Leu Glu Gin Ala Ser 225 230 235 240 Thr Ile Ile Thr Thr Leu Asn Ser Ala Cys Pro Trp Ile Asn Asn Gly 245 250 255 Gly Ala Gly Gly Ala Ser Ser Gly Ser Leu Trp Glu Gly Ile Tyr Leu 260 265 270 Lys Gly Asp Gly Ser Ala Cys Gly Ile Phe Lys Asn Glu Ile Ser Ala 275 280 285 Ile Gin Asp Met Ile Lys Asn Ala Ala Ile Ala Val Glu Gin Ser Lys 290 295 300 Ile Val Ala Ala Asn Ala Gin Asn Gin Arg Asn Leu Asp Thr Gly Lys 305 310 315 320 Thr Phe Asn Pro Tyr Lys Asp Ala Asn Phe Ala Gin Ser Met Phe Ala 325 330 335 Asn Ala Lys Ala Gin Ala Glu Ile Leu Asn Arg Ala Gin Ala Val Val 340 345 350 Lys Asp Phe Glu Arg Ile Pro Ala Glu Phe Val Lys Asp Ser Leu Gly 355 360 365 Val Cys His Glu Val Gin Asn Gly His Leu Arg Gly Thr Pro Ser Gly 370 375 380 Thr Val Thr Asp Asn Thr Trp Gly Ala Gly Cys Ala Tyr Val Gly Glu 385 390 395 400 Thr Val Thr Asn Leu Lys Asp Ser Ile Ala His Phe Gly Asp Gin Ala 405 410 415 Glu Arg Ile His Asn Ala Arg Asn Leu Ala Thr Leu 420 425 WO 98/24475 PCTIUS97/22104 184- INFORMATION FOR SEQ ID NO:103: SEQUENCE CHARACTERISTICS: LENGTH: 178 amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...178 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:103: Met Asn Pro Leu Led Gin Asp Tyr Ala Arg 1 Gin Gin Ser Ala Lys Asn Gin Ile Tyr 145 Cys Leu His Thr Leu Glu Ala Glu Asp 115 Lys Gly Met Asn 20 Asp Asp Lys Ala Ile 100 Leu Ser Glu His 5 Leu Ala Ile Pro Phe Ile Ile Gin Gin Gin 165 Ser Leu Gly Glu 70 Leu Lys Thr Arg Leu 150 Lys Gly Lys Ser Ala Asn Lys Ser Phe 135 Lys Arg Ala Pro 40 Gly Gin Tyr Arg Arg 120 Leu Asn Val Arg 25 Leu Ala Phe Leu Leu 105 Ala Lys Glu Tyr 10 Asn Glu Gly Ile Lys 90 Glu Val Asp Ile Phe 170 Ile Leu Leu Leu Ser Glu Phe Val Lys Leu Pro Ala Leu Leu Glu 75 Ser Val Leu Asp Tyr Gin Ala Ser Ser 125 Lys Gly Tyr 140 Ala Tyr Lys 155 Tyr Lys Ser Glu Leu Asp Ile Pro Pro Asn 110 Ser Phe Thr Lys Trp Glu Phe Pro Arg Leu Leu Phe Leu Thr Glu 175 Asn Pro Lys Leu Val Asn Leu Leu Phe Glu 160 Ser INFORMATION FOR SEQ ID NO:104: SEQUENCE CHARACTERISTICS: LENGTH: 240 amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein WO 98/24475 PTU9/20 PCTfUS97/22104 185- (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION .240 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:104: Leu Gly Leu Lys Lys Arg Ala Ile Leu Trp Ser Leu 1 Ala Lys Leu Gly Asn Gly Leu Gly Val1 145 Gly Val Al a Phe Glu 225 Leu Ile Arg Asn Ser Arg Lys 115 Ala Leu Tyr His Leu 195 Ile Trp Ser Lys Asp Thr Ser Phe 100 Pro Pro Asn Leu Gly 180 Ala Leu Trp Ala Tyr Leu Gly Ile Gly Asn Lys Gly Tyr 165 Val Leu Asn Gly Leu Tyr Lys Phe 70 Thr Tyr Ile Lys Asp 150 Met Asn Thr Asn Ala 230 Asp Lys Arg Phe Gly Gin Ile Ala 135 Phe Gly Tyr Val Phe 215 Ile Tyr Ala 40 Ala Tyr Asn Thr Gly 120 Gly Leu Gly Thr Leu 200 Pro Ala Asp 25 Tyr Asn Asn Ile Phe 105 Arg Phe Leu Tyr Al a 185 Glu Phe Ser Leu Asp Lys Glu 75 Asn Pro Ile Ser Phe 155 Gly Trp Asn Gin Gly 235 Met Pro Giu Gly Met Leu Phe Ile 125 Gly Leu Gly Met Ile 205 Asn Gin Gly Lys Vai Leu Val Phe Phe 110 Gin Phe Pro Leu Sen 190 Giu Ser Tyr Phe Tyr Glu Ile Lys Aia Al a Tyr Gin Phe Gly 175 Phe Phe Ser Val Cys Tyr Glu Leu Thr Tyr Arg Tyr Sen Val 160 Val Asn Giu Lys Phe 240 INFORMATION FOR SEQ ID NO:105: SEQUENC. 2HARACTERISTICS: LENGTH: 313 amino acids TYPE: amino acid TOPOLOGY: linear MOLECULE TYPE: protein HYPOTHETICAL: YES (ii) (iii) WO 98/24475 PTU9/20 PCTIUS97/22104 186- (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION .313 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:105: Leu Lys Leu Lys Tyr Trp Leu Val Tyr Leu Ala Phe 1 Gin Glu Pro Thr Phe Al a Tyr Ala Val 145 Gly Tyr Asp Ile Leu 225 Ile Arg Arg Glu Leu 305 Al a Lys Lys Tyr Ser Tyr Gly Pro 130 Pro Ala Val Phe G 1 210 Ile Giu Lys Met Arg 290 Leu Thr Ile 35 Glu Pro Ile Gly Ala 115 Val Tyr Leu Leu Lys 195 Leu Val Val His Gly 275 Leu Val Asp Asn Met Lys Al a Glu 100 Asn Ser Phe Lys Gly 180 Thr Met Gly Asp Arg 260 Val Leu Asn 5 Tyr Asn Asp Ile Asp Leu Ala Met Gly Glu 165 Ala Lys Leu Gly Tyr 245 Leu Glu Ile Tyr Asp Leu Lys Sen 70 Asp Asn Pro Ile Thr 150 Asn Met Lys Tyr Tyr 230 Thr Glu Glu Sen Ala 310 Asn Lys Asp 55 Ser Lys Leu Ser Ser 135 Arg Al a Asn His Gin 215 Ser Phe Ile Gly Ala 295 Phe Leu Arg Lys Lys Ser Sen Al a 120 Val Phe Leu Thr Phe 200 Asp Ser Asn Gly Ala 280 Asn Ile Glu 25 Gin Phe Lys Gly Tyr 105 Phe Lys Tyr Lys Asp 185 Leu Lys Pro Val Thr 265 Ile Asn Phe 10 Glu Leu Giu Arg Val 90 Gin Lys Phe Gly Gin 170 Leu Gly Pro Asn Gly 250 Lys Tyr Gin Glu Thr Giu Lys 75 Phe Gly Asn Gly Asp 155 Pro Leu Val Asn Phe 235 Val Leu His Phe Asn Glu Glu Lys Leu Glu Asn Tyr 140 Leu Val Phe Tyr Gin 220 Leu Ser Pro Asn Lys 300 Ile Gin Giy Leu Leu Gly Leu 110 Asn Lys Leu Ser Met 190 Gly Giy Lys Thr Ser 270 Giu Ser Gly Leu Val Giu Lys Gly Asp Ile Tyr Gly Phe 175 Pro Phe Arq Ser Leu 255 Tyr Asn Ser Leu Asp Ser Arg Ser Tyr Arg Asn Phe Gly 160 Phe Leu Gly Asn Leu 240 Tyr Leu Asp Phe INFORMATION FOR SEQ ID NO:i06: Wi SEQUENCE CHARACTERISTICS: LENGTH: 393 amino acids WO 98/24475PCIS7210 PCTfUS97/22104 187- TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc-feature LOCATION .393 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:106: Met Thr Sen Ala Ser Sen His Ser Phe Lys Giu Gin 1 Pro Cys Arg Thn Giu Asp Phe Val1 Lys 145 Pro Gin Lys Lys His 225 Ala Gin Leu Ile Ile Tyr Lys Val Glu Leu Asp 130 Giu Tyr Phe Giu Ile 210 Leu Leu Ile Asn Phe 20 Sen Leu Asn Asp Phe 100 Asp Ile Asp Gly Lys 180 Gin Tyr Gly Glu Pro 260 Leu 5 Ala Leu His Gin Ile Thn Leu Phe Glu Phe 165 Lys Leu Cys Val Pro 245 Trp Ala Phe Leu Ala Ile 70 Giu Lys Phe Cys Asn 150 Phe Ile Thr Ile Ala 230 Ile Thn Lys Asp Glu Leu 55 Thr Pro Ang Pro Asn 135 Tyr Tyr Leu Giu Phe 215 Asn Val Tyr Thr Ile 295 Lys Ser Val1 Giu Phe Phe Lys 120 Glu Phe Cys Giu Phe 200 Pro Al a Ile Pro Pro 280 Asn Ile Val Pro Leu Sen 105 Tyn Phe Tyr Asn Ile 185 Cys His Ile Gin Phe 265 Phe Leu Lys Leu Lys 75 Thr Met Lys Ala Val 155 Thr Arg Sen Tyr His 235 Asp Leu Sen Ile Al a Asn Glu Ile Val Met Asp 140 Tyr Tyr Al a Lys Ser 220 Asn Sen Lys Asp Asp Pro Asn Giu Phe Pro Leu Val1 125 Phe Asp Gin Gin Ile 205 Leu Thr His Ala Trp 285 His Gly Lys Asp Val Pro Lys Ser Asn Ile Lys 175 Ile Pro Glu Lys Tyr 255 Leu Tyr Ile Al a Ile Lys Leu Phe Tyr Asp Ile Tyr 160 Asn Asp Leu Glu G;in 240 Phe Trp Leu Ile Thr Gly Gly Gly Gly 290 Gly Gly GiU Lys Trp 300 His Tyr Tyr His WO 98/24475 PCT/US97/22104 188- Gly Ile Ala Ala Tyr His Tyr Tyr Phe Pro Leu Trp Lys Ala Glu Glu 305 310 315 320 Gin Ile Ala His Asp Ala Leu Lys Thr Phe Leu Lys His Tyr Phe Leu 325 330 335 His Ile His Glu Ile Pro Gin Asn Ala Arg Arg Arg Leu Phe Lys Tyr 340 345 350 Cys Ile Ser Ile Pro Leu Lys Ser Phe Ile Ser Lys Thr Leu Lys Phe 355 360 365 Leu Lys Leu His Ala Leu Val Lys Lys Ile Leu Ile Gin Leu Lys Leu 370 375 380 Leu Lys Lys Asn Gln Ser Gin Asn Phe 385 390 INFORMATION FOR SEQ ID NO:107: SEQUENCE CHARACTERISTICS: LENGTH: 435 amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...435 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:107: Leu Ile Phe Leu Lys Lys Ser Leu Cys Ala Leu 1 Phe Phe Trp Val Gin Thr Ile Lys Gin Ile Met Asn Gin Asn Met Val Lys 130 Phe Pro Ser Ser Leu Leu Tyr Pro 115 Leu Lys Pro Phe Leu Asp His Tyr 100 Arg Phe Pro 5 Leu Asn Thr Lys Thr 85 Gin Ser Trp Ala Lys Asn Met 55 Gin Tyr Ile Gin Ile 135 Asp Ala Leu 40 Gin Ala Ser Gly Ile 120 Asp Pro Ala Ala Gly Leu Tyr Ly 105 Gly Pro Asn 10 Ser Ser Arg Met Phe 90 Asn His Thr Arg Leu Val Pro Met Gly Tyr Arg Pro Arg 140 Trp Ile Tyr Asn Pro Ala Ser Phe Leu 125 Gly Asn Gly Leu Pro Ile Phe Gly Leu Ala Ala Trp 145 150 155 160 Glu Gly Val Val Asp Trp Tyr Gly Gly Arg Asn Trp Asn Asn Gin Pro WO 98/24475 PCTIUS97/22104 189- 165 170 175 Lys Lys Lys Asn Tyr Asp Phe Asp Gin Phe Leu Tyr Phe Val Ser Ser 180 185 190 Glu Phe Gin Phe Leu Lys Gly Tyr Leu Gly Leu Gly Gly Gin Leu Val 195 200 205 Ile Phe His Asn Ala Asn Ser His Ser Met Gly Asp Asn Tyr Pro Tyr 210 215 220 Gly Gly Asn Ser Tyr Leu Lys Pro Gly Asp Ala Thr Pro Gin Trp Pro 225 230 235 240 Asn Gly Tyr Pro Tyr Phe Ser Gin Lys Asp Asn Pro Gin Gly Gly Glu 245 250 255 Ile Gly Lys Tyr Ser Asn Pro Thr Ile Leu Asp Arg Val Tyr Tyr His 260 265 270 Ala Tyr Leu Lys Ala Asp Phe Lys Asn Leu Met Pro Tyr Met Asp Asn 275 280 285 Ile Phe Met Thr Phe Gly Thr Gin Ser Ser Gin Thr His Tyr Cys Val 290 295 300 Arg Tyr Ala Ser Glu Cys Lys Asn Ala Arg Phe Tyr Asn Ser Phe Gly 305 310 315 320 Gly Glu Phe Tyr Ala Gin Ala Gin Tyr Lys Gly Phe Gly Ile Phe Asn 325 330 335 Arg Tyr Tyr Phe Ser Asn Lys Pro Gin Met His Phe ryr Ala Thr Tyr 340 345 350 Gly Gin Ser Leu Tyr Thr Gly Leu Pro Trp Tyr Arg Ala Pro Asn Phe 355 360 365 Asp Met Ile Gly Leu Tyr Tyr Leu Tyr Lys Asn Lys Trp Leu Ser Val 370 375 380 Arg Ala Asp Ala Phe Phe Ser Phe Val Gly Gly Gly Asp Gly Tyr His 385 390 395 400 Leu Tyr Gly Lys Gly Gly Lys Trp Phe Val Met Tyr Gin Gin Phe Leu 405 410 415 Thr Leu Thr Ile Asp Thr Arg Glu Leu Ile Asp Phe Val Lys Ser Lys 420 425 430 Ile Pro Lys 435 INFORMATION FOR SEQ ID NO:108: SEQUENCE CHARACTERISTICS: LENGTH: 220 amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) .I'POTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc_feature LOCATION 1...220 WO 98/24475 PTU9/20 PCTIUS97/22104 -190- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:108: Met Asn Lys Thr Thr Ile Lys Ile Leu Met Gly Met 1 Ser Lys Ser Phe Ala Tyr Leu Leu Gly 145 Ser His Lys Leu Leu Phe Ala 50 Met Lys Asp Glu Gly 130 Gly Leu Asn Thr Pro 210 Gin Ala Ile Thr Thr Gin Phe 115 Leu Ala Phe Giu Glu 195 Val 5 Ala Arg Thr Asn Ala Phe Gly Phe His Leu 165 Thr Val Tyr Glu Asn Ser Gly 70 Val Ser Leu Gly Gly 150 Leu Phe Asp Phe Ala Thr Phe 55 Phe Glu Ser Trp Leu 135 Ile Val Gly Gly Asn 215 Glu Phe 40 Ser Gly His His Asp 120 Gly Ile Lys Leu Leu 200 Tyr Glu Gly Ser Leu 75 Phe Tyr Asn Gly Tyr 1!5 Phe Pro Thr Asn Lys Val Ile Gly Arg Ile Ser Ala 140 Leu Arg Val Thr Phe 220 Ala Ser Gly Asp Gly Tyr Ser Pro 125 Thr Gly Phe Ile Leu 205 Leu Lys Tyr Lys Lys Gly Thr 110 Lys Tyr Lys Gly Pro 190 Trp, Leu Lys Gin Ser Phe Leu Tyr Met Met Glu Phe 175 Asn Gin Ser Pro Leu Tyr Val Phe Gly Phe Pro Asn 160 Phe Lys Arg INFORMATION FOR SEQ ID NO:109: Wi SEQUENCE CHARACTERISTICS: LENGTH: 116 amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc Ifeature LOCATION .116 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:109: Leu Asn Leu His Phe Met Lys Gly Phe Val Met Ser Gly Leu Arg Thr 1 5 10 Phe Ser Cys Val Val Val Leu Cys Gly Ala Met Val Asn Val Ala Val WO 98/24475 PCTIUS97/22104 191- 25 Ala Gly Pro Lys Ile Glu Ala Arg Gly Glu Leu Gly Lys 40 Gly Ala Val Gly Asn Phe Val Gly Asp Lys Met Gly Gly 50 55 Gly Ala Ile Gly Gly Tyr Ile Gly Ser Glu Val Gly Asp 70 75 Asp Tyr Ile Arg Gly Val Asp Arg Glu Pro Gin Asn Lys 90 Thr Pro Arg Glu Pro Ile Arg Asp Phe Tyr Asp Tyr Gly 100 105 Gly His Ala Trp 115 INFORMATION FOR SEQ ID NO:110: SEQUENCE CHARACTERISTICS: LENGTH: 436 amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...436 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:110: Phe Val Gly Phe Val Gly Arg Val Glu Glu Pro Gin Tyr Ser Phe 110 Met Ser Arg Asp Phe Lys Phe Asp Ser Asn Tyr Leu 1 Asn Phe Asn Val Ser Pro Asn Lys Asn 145 Pro Ile Leu Gly Thr Tyr Tyr Leu 130 Lys Leu Asp Leu Arg Glu Leu 100 Ala Ile Pro 5 Gly His Val Phe Lys Ser Val Thr Glu Pro Leu Val Met 70 Thr Lys Trp Pro Lys 150 Val Arg Asn 55 Thr Asp Thr Leu Gly 135 His Thr 25 Tyr Asn Asp Ile Asn 105 Asp Arg Phe Gin Met Val Phe 75 Gly Asn Ile Thr Val 155 Asn Asn Lys Ile Val Gin Glu Phe 140 Trp Asn Tyr Ala Gin Arg Cys Glu Phe 125 Leu Thr Val Pro Phe Thr Ser F'is Met 110 Phe Asn Ser Asn Gly Glu Phe Asp Met Phe Asp Tyr Lys Thr Phe Pro Asn Gin Pro Asn Ser Asn Lys 160 WO 98/24475 PCT[~S97/22104 192- Gln Arg Gin Asn Glu Trp Ser Pro Ala Leu Asn Ile Gly Tyr Lys Pro 165 170 175 Met Glu Asn Trp Ile Trp Tyr Ala Asn Tyr Arg Arg Ser Phe Ile Pro 180 185 190 Pro Gin His Thr Met Val Gly Ile Thr Arg Thr Asn Tyr Asn Gin Ile 195 200 205 Phe Asn Glu Ile Glu Val Gly Gin Arg Tyr Ser Tyr Lys Asn Leu Leu 210 215 220 Ser Phe Asn Thr Asn Tyr Phe Val Ile Phe Ala Lys Arg Tyr Tyr Ala 225 230 235 240 Gly Gly Tyr Ser Pro Gin Pro Val Asp Ala Arg Ser Gin Gly Val Glu 245 250 255 Leu Glu Leu Tyr Tyr Ala Pro Ile Arg Gly Leu Gin Phe His Val Ala 260 265 270 Tyr Thr Tyr Ile Asp Ala Arg Ile Thr Ser Asn Ala Asp Asp Ile Ala 275 280 285 Tyr Tyr Phe Thr Gly Ile Val Asn Lys Pro Phe Asp Ile Lys Gly Lys 290 295 300 Arg Leu Pro Tyr Val Ser Pro Asn Gin Phe Ile Phe Asp Met Met Tyr 305 310 315 320 Thr Tyr Lys His Thr Thr Phe Gly Ile Ser Ser Tyr Phe Tyr Ser Arg 325 330 335 Ala Tyr Ser Ser Met Leu Asn Gin Ala Lys Asp Gin Thr Val Cys Leu 340 345 350 Pro Leu Asn Pro Glu Tyr Thr Gly Gly Leu Lys Tyr Gly Cys Asn Ser 355 360 365 Val Gly Leu Leu Pro Leu Tyr Phe Val Leu Asn Val Gin Val Ser Ser 370 375 380 Ile Leu Trp Gin Ser Gly Arg His Lys Ile Thr Gly Ser Leu Gin Ile 385 390 395 400 Asn Asn Leu Phe Asn Met Lys Tyr Tyr Phe Arg Gly Ile Gly Thr Ser 405 410 415 Pro Thr Gly Arg Glu Pro Ala Pro GlyArg Ser Ile Thr Ala Tyr Leu 420 425 430 Asn Tyr Glu Phe 435 INFORMATION FOR SEQ ID NO:111: SEQUENCE CHARACTERISTICS: LENGTH: 767 amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: prot!in (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc_feature LOCATION 1...767 WO 98/24475 PTU9/20 PCT/US97/22104 -193- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:lll: Met Lys Arg Ile Leu Val Ser Leu Ala Val Leu Ser His Ser Ala His 1L 5 10 Ala Val Lys Thr His Asn Leu Giu Arg Val Glu Ala Ser Gly Val Ala 25 Asn Asp Lys Glu Ala Pro Leu Ser Trp Arg Ser Lys Giu Val Arg Asn 40 Tyr met Gly Ser Arg Thr Val Ile Ser Asn Lys Gin Leu Thr Lys Ser 55 Ala Asn Gin Ser Ile Giu Giu Ala Leu Gin Asn Val Pro Gly Val His 70 75 Ilie Arg Asn Ser Thr Gly Ile Gly Ala Val Pro Ser Ile Ser Ile Arg 85 90 Giy Phe Giy Ala Gly Gly Pro Giy His Ser Asn Thr Gly Met Ile Leu 100 105 110 Val Asn Gly Ile Pro Ile Tyr Val Ala Pro Tyr Val Giu Ile Giy Thr 115 120 125 Val Ile Phe Pro Val Thr Phe Gin Ser Val Asp Arg Ile Ser Val Thr 130 135 140 Lys Gly Gly Giu Ser Vai Aig Tyr Gly Pro Asn Ala Phe Gly Gly Val 145 150 155 160 Ile Asn Ile Ile Thr Lys Gly Ile Pro Thr Asn Trp Giu Ser Gin Val 165 170 175 Ser Giu Arg Thr Thr Phe Trp Gly Lys Ser Giu Asn Gly Gly Phe Phe 180 185 190 Asn Gin Asn Ser Lys Asn Ile Asp Lys Ser Leu Val Asn Asn Met Leu 195 200 205 Phe Asn Thr Tyr Leu Arg Thr Gly Gly Met Met Asn Lys His Phe Gly 210 215 220 Ile Gin Ala Gin Val Asn Trp Leu Lys Gly Gin Gly Phe Arg Tyr Asn 225 230 235 240 Ser Pro Thr Asp Ile Gin Asn Tyr Met Leu Asp Ser Leu Tyr Gin Ile 245 250 255 Asn Asp Se Asn Tvs Ile Thr Ala Phe Phe Gin Tyr Tyr Ser Tyr Phe 260 265 270 Leu Thr Asp Pro Gly Ser Leu Gly Ile Ala Ala Tyr Asn Gin Asn Arg 275 280 285 Phe Gin Asn Asn Arg Pro Asn Asn Asp Lys Ser Gly Arg Ala Lys Arg 290 295 300 Trp Gly Ala Val Tyr Gin Asn Phe Phe Gly Asp Thr Asp Arg Val Gly 305 310 315 320 Gly Asp Phe Thr Phe Ser Tyr Tyr Gly His Asp Met Ser Arg Asp Phe 325 330 335

L

1 F Phe Asp Ser Asn Tyr Leu Asn Vai Asn Thr Asn Pro Lys Leu Gly 340 345 350 Pro Val Tyr Thr Asn Gin Asn Tyr Pro Gly Phe Phe Ile Phe Asp His 355 360 365 Leu Arg Arg Tyr Val Met Asn Ala Phe Giu Pro Asn Leu Asn Leu Val 370 375 380 Val Asn Thr Asn Lys Val Lys Gin Thr Phe Asn Val Gly Met Arg Phe 385 390 395 400 Met Thr Met Asp Met Phe Ile Arg Ser Asp Gin Ser Thr Cys Glu Lys WO 98/24475 PCT/US97/22104 -194- 405 410 415 Thr Asp Ile Ile Asn Gly Val Cys His Met Pro Pro Tyr Val Leu Ser 420 425 430 Lys Thr Pro Asn Asn Asn Gin Glu Met Phe Asn Asn Tyr Thr Ala Val 435 440 445 Trp Leu Ser Asp Lys Ile Glu Phe Phe Asp Ser Lys Leu Val Ile Thr 450 455 460 Pro Gly Leu Arg Tyr Thr Phe Leu Asn Tyr Asn Asn Lys Glu Pro Glu 465 470 475 480 Lys His Asp Phe Ser Val Trp Thr Ser Lys Lys Gin Arg Gin Asn Glu 485 490 495 Trp Ser Pro Ala Leu Asn Ile Gly Tyr Lys Pro Met Glu Asn Trp Ile 500 505 510 Trp Tyr Ala Asn Tyr Arg Arg Ser Phe Ile Pro Pro Gin His Thr Met 515 520 525 Val Gly Ile Thr Arg Thr Asn Tyr Asn Gin Ile Phe Asn Glu Ile Glu 530 535 540 Val Gly Gin Arg Tyr Ser Tyr Lys Asn Leu Leu Ser Phe Asn Thr Asn 545 550 555 560 Tyr Phe Val Ile Phe Ala Lys Arg Tyr Tyr Ala Gly Gly Tyr Ser Pro 565 570 575 Gin Pro Val Asp Ala Arg Ser Gin Gly Val Glu Leu Glu Leu Tyr Tyr 580 585 590 Ala Pro Ile Arg Gly Leu Gin Phe His Val Ala Tyr Thr Tyr Ile Asp 595 600 605 Ala Arg Ile Thr Ser Asn Ala Asp Asp Ile Ala Tyr Tyr Phe Thr Gly 610 615 620 Ile Val Asn Lys Pro Phe Asp Ile Lys Gly Lys Arg Leu Pro Tyr Val 625 630 635 640 Ser Pro Asn Gin Phe Ile Phe Asp Met Met Tyr Thr Tyr Lys His Thr 645 650 655 Thr Phe Gly Ile Ser Ser Tyr Phe Tyr Ser Arg Ala Tyr Ser Ser Met 660 665 670 Leu Asn Gin Ala Lys Asp Gin Thr Val Cys Leu Pro Leu Asn Pro Glu 675 680 685 Tyr Thr Gly Gly Leu Lys Tyr Gly Cys Asn Ser Val Gly Leu Leu Pro 690 695 700 Leu Tyr Phe Val Leu Asn Val Gin Val Ser Ser Ile Leu Trp Gin Ser 705 710 715 720 Gly Arg His Lys Ile Thr Gly Ser Leu Gin Ile Asn Asn Leu Phe Asn 725 730 735 Met Lys Tyr Tyr Phe Arg Gly Ile Gly Thr Ser Pro Thr Gly Arg Glu 740 745 750 Pro Ala Pro Gly Arg Ser Ile Thr Ala Tyr Leu Asn Tyr Glu Phe 755 760 765 INFORMATION FOR SEQ ID NO:112: SEQUENCE CHARACTERISTICS: LENGTH: 115 amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein WO 98/24475 PCT/US97/22104 195- (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: miscfeature LOCATION 1...115 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:112: Leu His Pro Leu Cys Ala His Gly Gin Cys Gly Ser Glu Ala Ile Ala 1 5 10 Cys Leu Glu Ala Ile Ser Val Gly Ile Val Pro Val Ile Ala Asn Ser 25 Pro Leu Ser Ala Thr Arg Gln Phe Ala Leu Asp Glu Arg Ser Leu Phe 40 Glu Pro Asn Asn Ala Lys Asp Leu Ser Ala Lys Ile Asp Trp Trp Leu 50 55 Glu Asn Lys Leu Glu Arg Glu Arg Met Gin Asn Glu Tyr Ala Lys Ser 70 75 Ala Leu Asn Tyr Thr Leu Glu Asn Ser Val Ile Gin Ile Glu Lys Val 90 Tyr Glu Glu Ala Ile Lys Asp Phe Lys Asn Asn Pro Asn Leu Phe Lys 100 105 110 Thr Leu Ser 115 INFORMATION FOR SEQ ID NO:113: SEQUENCE CHARACTERISTICS: LENGTH: 389 amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...389 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:113: Met Val Ile Val Leu Val Val Asp Ser Phe Lys Asp Thr Ser Asn Gly 1 5 10 Thr Ser Met Thr Ala Phe Arg Phe Phe Glu Ala Leu Lys Lys Arg Gly 25 His Ala Met Arg Val Val Ala Pro His Val Asp Asn Leu Gly Ser Glu WO 98/24475 PCT[S97/22104 -196- 40 Glu Glu Gly Tyr Tyr Asn Leu Lys Glu Arg Tyr Ile Pro Leu Val Thr 55 Glu Ile Ser His Lys Gin His Ile Leu Phe Ala Lys Pro Asp Glu Lys 65 70 75 Ile Leu Arg Lys Ala Phe Lys Gly Ala Asp Met Ile His Thr Tyr Leu 90 Pro Phe Leu Leu Glu Lys Thr Ala Val Lys Ile Ala Arg Glu Met Arg 100 105 110 Val Pro Tyr Ile Gly Ser Phe His Leu Gin Pro Glu His Ile Ser Tyr 115 120 125 Asn Met Lys Leu Gly Gin Phe Ser Trp Leu Asn Thr Met Leu Phe Ser 130 135 140 Trp Phe Lys Ser Ser His Tyr Arg Tyr Ile His His Ile His Cys Pro 145 150 155 160 Ser Lys Phe Ile Val Glu Glu Leu Glu Lys Tyr Asn Tyr Gly Gly Lys 165 170 175 Lys Tyr Ala Ile Ser Asn Gly Phe Asp Pro Met Phe Lys Phe Glu His 180 185 190 Pro Gin Lys Ser Leu Phe Asp Thr Thr Pro Phe Lys Ile Ala Met Val 195 200 205 Gly Arg Tyr Ser Asn Glu Lys Asn Gin Ser Val Leu Ile Lys Ala Val 210 215 220 Ala Leu Ser Arg Tyr Lys Gin Asp Ile Val Leu Leu Leu Lys Gly Lys 225 230 235 240 Gly Pro Asp Glu Lys Lys Ile Lys Leu Leu Ala Gin Lys Leu Gly Val 245 250 255 Lys Thr Glu Phe Gly Phe Val Asn Ser His Glu Leu Leu Glu Ile Leu 260 265 270 Lys Thr Cys Thr Leu Tyr Ala His Thr Ala Asn Val Glu Ser Glu Ala 275 280 285 Ile Ala Cys Leu Glu Ala Ile Ser Val Gly Ile Val Pro Val Ile Ala 290 295 300 Asn Ser Pro Leu Ser Ala Thr Arg Gin Phe Ala Leu Asp Glu Arg Ser 305 310 315 320 Leu Phe Glu Pro Asn Asn Ala Lys Asp Leu Ser Ala Lys Ile Asp Trp 325 330 335 Trp Leu Glu Asn Lys Leu Glu Arg Glu Arg Met Gin Asn Glu Tyr Ala 340 345 350 Lys Ser Ala Leu Asn Tyr Thr Leu Glu Asn Ser Val Ile Gin Ile Glu 355 360 365 Lys Val Tyr Glu Glu Ala Ile Lys Asp Phe Lys Asn Asn Pro Asn Leu 370 375 380 Phe Lys Thr Leu Ser 385 INFORMATION FOR SEQ ID NO:114: SEQUENCE CHARACTERISTICS: LENGTH: 312 amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein WO 98/24475 PCTfUS97/22104 -197- (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...312 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:114: Leu Ala Ser Tyr Gly Phe Phe Leu Gly Ala Leu Phe Ile Leu Ala Ser 1 5 10 Gly Ile Val Cys Leu Gin Thr Ala Gly Asn Pro Phe Val Thr Leu Leu 25 Ser Lys Gly Lys Glu Ala Arg Asn Leu Val Leu Val Gin Ala Phe Asn 40 Ser Leu Gly Thr Thr Leu Gly Pro Ile Phe Gly Ser Leu Leu Ile Phe 50 55 Ser Ala Thr Lys Thr Ser Asp Asn Leu Ser Leu Ile Asp Lys Leu Ala 70 75 Asp Ala Lys Ser Val Gin Met Pro Tyr Leu Gly Leu Ala Val Phe Ser 90 Leu Leu Leu Ala Leu Val Met Tyr Leu Leu Lys Leu Pro Asp Val Glu 100 105 110 Lys Glu Met Pro Lys Glu Thr Thr Gin Lys Ser Leu Phe Ser His Lys 115 120 125 His Phe Val Phe Gly Ala Leu Gly Ile Phe Phe Tyr Val Gly Gly Glu 130 135 140 Val Ala Ile Gly Ser Phe Leu Val Leu Ser Phe Glu Lys Leu Leu Asn 145 150 155 160 Leu Asp Ala Gin Ser Ser Ala His Tyr Leu Val Tyr Tyr Trp Gly Gly 165 170 175 Ala Met Val Gly Arg Phe Leu Gly Ser Ala Leu Met Asn Lys Ile Ala 180 185 190 Pro Asn Lys Tyr Leu Ala Phe Asn Ala Leu Ser Ser Ile Ile Leu Ile 195 200 205 Ala Leu Ala Ile Leu Ile Gly Gly Lys Ile Ala Leu Phe Ala Leu Thr 210 215 220 Phe Val Gly Phe Phe Asn Ser Ile Met Phe Pro Thr Ile Phe Ser Leu 225 230 235 240 Ala Thr Leu Asn Leu Gly His Leu Thr Ser Lys Ala Ser Gly Val Ile 245 250 255 Ser Met Ala Ile Val Gly Gly Ala Leu Ile Pro Pro Ile Gin Gly Val 260 265 270 Val Thr Asp Met Leu Thr Ala Thr Glu Ser Asn Leu Leu Tyr Ala Tyr 275 280 285 Ser Val Pro Leu Leu Cys Tyr Phe Tyr Ile Leu Phe Phe Ala Leu Lys 290 295 300 Gly Tyr Lys Gin Glu Glu Asn Ser 305 310 INFORMATION FOR SEQ ID NO:115: WO 98/24475 PCT/US97/22104 -198- SEQUENCE CHARACTERISTICS: LENGTH: 407 amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...407 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:115: Met Gin Lys Thr Ser Asn Thr Leu Ala Leu Gly Ser Leu Thr Ala Leu 1 5 10 Phe Phe Leu Met Gly Phe Ile Thr Val Leu Asn Asp Ile Leu Ile Pro 25 His Leu Lys Pro Ile Phe Asp Leu Thr Tyr Phe Glu Ala Ser Leu Ile 35 40 Gin Phe Cys Phe Phe Gly Ala Tyr Phe Ile Met Gly Gly Val Phe Gly 55 Asn Val Ile Ser Lys Ile Gly Tyr Pro Phe Gly Val Val Leu Gly Phe 70 75 Val Ile Thr Ala Ser Gly Cys Ala Leu Phe Tyr Pro Ala Ala His Phe 90 Gly Ser Tyr Gly Phe Phe Leu Gly Ala Leu Phe Ile Leu Ala Ser Gly 100 105 110 Ile Val Cys Leu Gin Thr Ala Gly Asn Pro Phe Val Thr Leu Leu Ser 115 120 125 Lys Gly Lys Glu Ala Arg Asn Leu Val Leu Val Gin Ala Phe Asn Ser 130 135 140 Leu Gly Thr Thr Leu Gly Pro Ile Phe Gly Ser Leu Leu Ile Phe Ser 145 150 155 160 Ala Thr Lys Thr Ser Asp Asn Leu Ser Leu Ile Asp Lys Leu Ala Asp 165 170 175 Ala Lys Ser Val Gin Met Pro Tyr Leu Gly Leu Ala Val Phe Ser Leu 180 185 190 Leu Leu Ala Leu Val Met Tyr Leu Leu Lys Leu Pro Asp Val Glu Lys 195 200 205 Glu Met Pro Lys Glu Thr Thr Gin Lys Ser Leu Phe Ser His Lys 3 210 215 220 Phe Val Phe Gly Ala Leu Gly Ile Phe Phe Tyr Val Gly Gly Glu Val 225 230 235 240 Ala Ile Gly Ser Phe Leu Val Leu Ser Phe Glu Lys Leu Leu Asn Leu 245 250 255 Asp Ala Gin Ser Ser Ala His Tyr Leu Val Tyr Tyr Trp Gly Gly Ala 260 265 270 Met Val Gly Arg Phe Leu Gly Ser Ala Leu Met Asn Lys Ile Ala Pro WO 98/24475 PCT/US97/22104 199- 275 280 Asn Lys Tyr Leu Ala Phe Asn Ala Leu Ser Ser Ile 290 295 300 Leu Ala Ile Leu Ile Gly Gly Lys Ile Ala Leu Phe 305 310 315 Val Gly Phe Phe Asn Ser Ile Met Phe Pro Thr Ile 325 330 Thr Leu Asn Leu Gly His Leu Thr Ser Lys Ala Ser 340 345 Met Ala Ile Val Gly Gly Ala Leu Ile Pro Pro Ile 355 360 Thr Asp Met Leu Thr Ala Thr Glu Ser Asn Leu Leu 370 375 380 Val Pro Leu Leu Cys Tyr Phe Tyr Ile Leu Phe Phe 385 390 395 Tyr Lys Gin Glu Glu Asn Ser 405 INFORMATION FOR SEQ ID NO:116: SEQUENCE CHARACTERISTICS: LENGTH: 125 amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...125 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:116: Met Asn Lys Ile Ala Pro Asn Lys Tyr Leu Ala Phe i 5 10 Ser Ile Ile Leu Ile Ala Leu Ala Ile Leu Ile Gly 25 Leu Phe Ala Leu Thr Phe Val Gly Phe Phe Asn Ser 40 Thr Ile Phe Ser Leu Ala Thr Leu Asn Leu Gly Ile 55 Ala Ser Gly Val Ile Ser Met Ala Ile Val Gly Gly 70 75 Pro Ile Gin Gly Val Val Thr Asp Met Leu Thr Ala 85 90 Leu Leu Tyr Ala Tyr Ser Val Pro Leu Leu Cys Tyr 100 105 Phe Phe Ala Leu Lys Gly Tyr Lys Gin Glu Glu Asn 115 120 285 Ile Ala Phe Gly Gin 365 Tyr Ala Gly Gly Ile Ser Ala Thr Phe Ser 125 Leu Leu Ser Val 350 Gly Ala Leu Ala Lys Met Leu Leu Glu Tyr 110 Ile Thr Leu 335 Ile Val Tyr Lys Leu Ile Phe Leu Ile Ser Ile Ala Phe 320 Ala Ser Val Ser Gly 400 Ser Ala Pro Met Pro Asn Leu WO 98/24475 PTU9/20 PCTIUS97/22104 200 INFORMATION FOR SEQ ID NO:117: SEQUENCE CHARACTERISTICS: LENGTH: 330 amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION .330 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:117: Leu Lys Lys Ile Leu Pro Ala Leu Leu Met Gly 1 Al a Leu Phe Gin Glu Lys Leu Leu Leu 145 GJ1y Ile Giy Thr Giu 225 Pro Ser Giu Trp Asn Phe Ala Al a Asp 130 Tyr Met Ala Giu Lys 210 Al a Asn Asp Val Ala Lys Tyr Leu Thr 115 Gin Asp Pro Ile Ly-, 195 Glu Trp Phe Arg 20 Val Giu Gin Glu Val 100 Pro Tyr Thr Leu Giu 190g li a Glu Ala Thr 5 Leu Gly Giu Phe Ile Gly Ile Tyr Leu Asn 165 Asn Phe Leu Arg Arg Leu Gln Leu Leu 70 Glu Ser Gly Gly Lys 150 Gly Pro Leu Ser Gly 230 Tyr Giu Lys Gin Phe Asn Lys Val Val 135 Lys Asp Ile Ile Met 215 Asp Asp Ile Leu Asn Val Asn Lys Tyr 120 Leu Arg Arg Leu Thr 200 Ile Phe Gly Met 25 Asp Lys Ala Met Gly 105 Arg Ala Thr Asn Ser 185 Tyr Leu Giu Met Leu Tyr Thr Lys 75 Lys Lys Thr Val His 155 Leu Tyr Asp Ser Tyr 235 Phe Phe Tyr Leu Asp Ser Lys Thr Gin Thr 140 Gly Asn Asp Lys Leu 220 Met Asn Gly Lys Asp Gly Pro Asn Glu 110 Leu Tyr Trp Lys Val 190 Ser Gln Phe Phe Leu Gin Lys Tyr Ser Ser Gly Glu Pro Val Gly 175 Leu Pro Trp Tyr Lys Asn Gly Ser Tyr Leu Ser Asp Arg Asn His 160 Cys Lys Ser Lys Asn 240 Glu 245 250 255 Tyr Lys Lys Arg Val Phe Ala Lys Asn Giu Lys Lys Asn Ile Ala Phe WO 98/24475 PTU9/20 PCT/US97/22104 -201- 260 265 Ser Ser Ile Asn Val Ile Pro Tyr Pro Asn Ser G 275 280 Phe Tyr Val Val Phe Asp Gin Asp Tyr Lys Ala T 290 295 3 Leu Ser Tyr Ser Ser Asn Ser Gin Lys Giu Leu T 305 310 315 Asn Asn Gin Aia Ser Ile Ile Met Giu Lys 325 330 INFORMATION FOR SEQ ID NO:i18: SEQUENCE CHARACTERISTICS: LENGTH: 169 amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY:. misc feature LOCATION .169 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:ii8: 270 in Asn Lys Arg Leu 285 yr Gin Gin Asn Lys 00 yr Vai Gu Ile Giu 320 Leu Phe Giu Lys Trp Ile Giy Leu Thr Leu Leu Leu Ser Ser Leu Gly 1 Tyr Ile Leu Arg 65 Leu Lys Gin Lys Gly 145 Ile Pro His Ile Giu Asn Thr Ile Ser 130 Met Tyr Cys Ile Ser Lys Thr Lys Leu 115 Val Lys Ser Gin His Ile Ser Ala Leu 100 Lys Tyr His Gin 5 Lys Gin Ala Leu Lys Leu Giu Gin Asn Val 165 Val Lys Leu Lys 70 Lys Asn Asn Leu Pro 150 Arg Ser Gly Leu 55 Asp Phe Asp Phe Val 135 Asn Tyr Ile Cys Giu Thr Tyr Val Asp 120 Gin Gly Asn Ser 25 Asn Ser Ser Pro Gly 105 Tyr Met Ala Glu 10 Phe Asn Ser Tyr Thr 90 Phe Tyr Al a Tyr Lys Glu Leu Ser 75 Tyr Ala His Ile Met 155 Gin Val Gly Met S er Ile Gin Gly 140 Lys Glu Cys Asn His Thr Leu His Tyr Phe Asn Arg Asn Ile Leu Aia Pro Asn Arg Leu Thr Lys Thr Leu Lys Asn Gly Cys 160 INFORMATION FOR SEQ ID NO:119: WO 98/24475 PCT/US97/22104 -202- SEQUENCE CHARACTERISTICS: LENGTH: 215 amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...215 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:119: Met Lys Lys Pro Tyr Arg Lys Ile Ser Asp Tyr Ala 1 Leu Asp Gly Val Gin Lys Pro Ala Asn 145 Tyr Ser Gly Gly Ser Asp Ala Glu Gly Glu Asn Ile 130 Lys Lys Ala Phe Thr 210 Ala Lys 35 Phe Glu Asn Glu Asn 115 Leu Leu Ser Pro Phe 195 Arg Leu Pro Val Tyr Glu Glu 100 Gly Gly Phe Pro Ser 180 Gly Gly 5 Val Lys Ile Pro Arg Ala Gly Ser Asn Gin 165 Ala Ser Phe Met Glu Leu Ser 70 Val Lys Ser Ala Asn 150 Ala Ser Ser Asn Val Gin Glu 55 Ser Leu Ile Asn Ala 135 Pro Tyr Ser Arg Ala 215 Ser Ser 40 Glu Arg Ser Asp Glu 120 Gly Asn Gin Met Pro 200 Ile 25 Ser Gln Thr Asn Asn 105 Gly Ala Tyr Arg Gly 185 Thr 10 Val Leu Lys His Glu 90 Gly Ser Ile Gin Ser 170 Thr Ser Gly Ser Asp Ile Glu Thr Gly Leu Gin 155 Gin Ala Ser Cys Gin Lys Val Ile Ser Phe Gly 140 Asn Asn Ser Pro Ile Lys Ser Ser Val Gin Lys Gly 125 Ser Ala Ser Lys Ala 205 Val Ser Val Tyr Arg Lys Leu 110 Leu Tyr Gln Phe Gly 190 Ile Gly Asn Gin Lys Asp Leu Val Gly Ile Arg Ser 175 Gin Ser INFORMATION FOR SEQ ID NO:120: SEQUENCE CHARACTERISTICS: LENGTH: 253 amino acids TYPE: amino acid TOPOLOGY: linear WO 98/24475 WO 9824475PCTIUS97/22104 -203- (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION .253 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:120: Leu Lys Thr Leu Phe Ser Val Tyr Leu Phe Leu Ser 1.

Phe Lys Asn Arg Tyr Ala Arg Phe Tyr 145 Tyr Leu Thr Asp Val 225 Pro Leu Asn Asn Ala Ser Asn Asn His 130 Gly Arg Val Lys Phe 210 Arg Arg Giu Lys 35 Giu Leu Gin Ser His 115 Sen Gly Phe Asp Lys 195 Ile Asn Phe Al a Asn Lys Giu Al a Ile 100 Pro Val Ala Arg Thr 180 Thr Gly Val Asn 5 Lys Glu Gin Lys Ala Gly Lys Ser Leu Sen 165 Ile Phe Tyn Phe Ala 245 Giu Asp Gin Sen 70 Tyr Phe Val Leu Asp 150 Tyr Lys Phe Leu.

Tyr 230 Asn Ile Asp Ile Leu Sen Asn Gly Ser 135 Phe Leu Thr Gin Ser 215 Thr Leu Thr Lys 40 Leu Lys Thn Thr Phe 120 Gin Sen Gly Gly Ala 200 Leu.

Tyr Se-- Trp 25 Pro Asp Phe Thr Ala 105 Arg Pro Trp Ile Ser 185 Pro Gin Asn Leu 10 Ser Lys Lys Phe Asn 90 Thr Ile Gin Ile Ala 170 Phe Leu Leu Asn Ile 250 Gin Pro Asn Phe 75 Gin Gly Phe Ile Phe 155 Leu Thr Arg Gly His 235 Val Leu Leu.

Thr Gin Phe Leu Giu Val 125 Met Asp Gin Ile Gly 205 Giu Giu Phe Asn Giu Ile Ile Gly Thr His 110 Tyr Vai Lys Giy Ile 190 Phe Met Arg Pro Asn Asp Leu Tyr Leu Phe Asn Gin Lys Val 175 Pro Ile Pro Phe Leu Phe Lys Lys Asn.

Thr Leu Tyr Asn Thr 160 Leu Arg Val Leu Lys 240 INFORMATION FOR SEQ ID NO:i21: SEQUENCE CHARACTERISTICS: LENGTH: 336 amino acids TYPE: amino acid TOPOLOGY: linear WO 98/24475 PCT/US97/22104 -204- (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...336 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:121: Leu Phe Phe Lys Phe Ile Leu Cys Leu Ser Leu Gly Ile Phe Ala Trp 1 5 1o Ala Lys Glu Val Ile Pro Thr Pro Ser Thr Pro Leu Thr Pro Ser Lys 25 Arg Tyr Ser Ile Asn Leu Met Thr Glu Asn Asp Gly Tyr Ile Asn Pro 40 Tyr Ile Asp Glu Tyr Tyr Thr Ala Gly Asn Gin Ile Gly Phe Ser Thr 55 Lys Glu Phe Asp Phe Ser Lys Asn Lys Ala Met Lys Trp Ser Ser Tyr 70 75 Leu Gly Phe Phe Asn Lys Ser Pro Arg Val Thr Arg Phe Gly Ile Ser 85 90 Leu Ala Gin Asp Met Tyr Thr Pro Ser Leu Ala Asn Arg Lys Leu Val 100 105 110 His Leu His Asp Asn His Pro Tyr Gly Gly Tyr Leu Arg Val Asn Leu 115 120 125 Asn Val Tyr Asn Arg His Gin Thr Phe Met Glu Leu Phe Thr Ile Ser 130 135 140 Leu Gly Thr Thr Gly Gin Asp Ser Leu Ala Ala Gin Thr Gin Arg Leu 145 150 155 160 Ile His Lys Trp Gly His Asp Pro Gin Phe Tyr Gly Trp Asn Thr Gin 165 170 175 Leu Lys Asn Glu Phe Ile Phe Glu Leu His Tyr Gin Leu Leu Lys Lys 180 185 190 Val Pro Leu Leu Lys Thr Arg Phe Phe Ser Met Glu Leu Met Pro Gly 195 200 205 Phe Asn Val Glu Leu Gly Asn Ala Arg Asp Tyr Phe Gin Leu Gly Ser 210 215 220 Leu Phe Arg Ala Gly Tyr Asn Leu Asp Ala Asp Tyr Gly Val Asn Lys 225 230 235 240 Val Asn Thr Ala Phe Asp Gly Gly Met Pro Tyr Ser Asp Lys Phe Ser 245 250 255 Ile 2 r Phe Phe Ala Gly Ala Phe Gly Arg Phe Gin Pro Leu Asn Ile 260 265 270 Phe Ile Gin Gly Asn Ser Pro Glu Thr Arg Gly Ile Ala Asn Leu Glu 275 280 285 Tyr Phe Val Tyr Ala Ser Glu Ile Gly Ala Ala Met Met Trp Arg Ser 290 295 300 Leu Arg Val Ala Phe Thr Ile Thr Asp Ile Ser Lys Thr Phe Gin Ser 305 310 315 320 Gin Pro Lys His His Gin Ile Gly Thr Leu Glu Leu Asn Phe Ala Phe WO 98/24475 PCT/US97/22104 -205- 325 330 335 INFORMATION FOR SEQ ID NO:122: SEQUENCE CHARACTERISTICS: LENGTH: 108 amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc_feature LOCATION 1...108 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:122: Met Lys Pro Ile Phe Ser Leu Phe Phe Leu Leu Ile Val Leu Lys Ala 1 5 10 His Pro Ile Asn Pro Leu Leu Glu Pro Leu Tyr Phe Pro Ser Tyr Thr 25 Gln Phe Leu Asp Leu Glu Pro His Phe Val Ile Lys Lys Lys Arg Ala 40 Tyr Arg Pro Phe Gin Trp Gly Asn Thr Ile Ile Ile Lys Arg His Asp 50 55 Leu Glu Glu Arg Gin Ser Asn Gin Pro Ser Asp Ile Phe Arg Gin Asn 70 75 Ala Glu Ile Asn Val Ser Ser Gin Thr Phe Leu Arg Gly Ile Ser Ser 90 Ala Ser Ser Arg Ile Val Ile Asp Ser Val Ala Gin 100 105 INFORMATION FOR SEQ ID NO:123: SEQUENCE CHARACTERISTICS: LENGTH: 195 amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc_feature LOCATION 1...195 WO 98/24475 -206- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:123: Met Ser Asn Asn Pro Phe Lys Lys Val Gly Met Ile PCT/US97/22 104 Asfl Phe Asp Asp Asn Gly Asn Asn Al a 145 Gly Thr Phe Asn Phe Tyr Ile Asp Gly Leu Phe 130 Lys Ile Lys Al a Gly Gly Asn Trp Ser Ile Thr 115 Gin Lys Lys Leu Tyr 195 Ala Glu His Thr Ile Gin 100 Ala Phe Lys Ile Glu 180 Asn Lys Tyr Gly 70 Arg Ala Asn Phe Ser 150 Thr Arg Gly Arg Ile Giy Lys Gly Asn Asn 135 Giu Ile Arg Gly 25 Gly Ser Ser Asn Thr 105 Tyr Gly Ser Thr Tyr 185 Gin Arg Phe Leu Leu Leu Ala Arg Gin 155, Tyr Val Ser Gly Tyr Asn Val Val Ser Val 125 Asn Gly Ser Leu Ser Tyr Gly Ser Asn Gly Gin 110 Asn Leu Val Phe Asn 190 Gin Lys Phe Ser Phe Leu Tyr Ala Ala Giu Leu 175 Tyr INFORMATION FOR SEQ ID NO:124: Wi SEQUENCE CHARACTERISTICS: LENGTH: 227 amino acids TYPE: amino acid In) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION .227 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:124: Val Arg Phe Gly Lys Ile Asp Tyr Leu Asn Met Leu Pro Phe Asp Val 1 5 10 Phe Ile Lys Ser Tyr Pro Thr Pro Cys Tyr Phe Lys Gin Phe Leu Arg 25 WO 98/24475 PCTITS97/22104 -207- Leu Lys Lys Thr Tyr Pro Ser Lys Leu Asn Glu Ser Phe Leu Phe Arg 40 Arg Ile Asp Ala Gly Phe Ile Ser Ser Ile Ala Gly Tyr Pro Phe Ala 55 Leu Cys Ser Tyr Ser Leu Gly Ile Val Ala Tyr Lys Glu Val Leu Ser 70 75 Val Leu Val Val Asn Arg Glu Asn Ala Phe Asp Lys Glu Ser Ala Ser 90 Ser Asn Ala Leu Ser Lys Val Leu Gly Leu Lys Gly Glu Val Leu Ile 100 105 110 Gly Asn Lys Ala Leu Gin Phe Tyr Tyr Ser Asn Pro Lys Lys Asp Phe 115 120 125 Ile Asp Leu Ala Ala Leu Trp Tyr Glu Lys Lys Arg Leu Pro Phe Val 130 135 140 Phe Gly Arg Leu Cys Tyr Tyr Gin Asn Lys Asp Phe Tyr Lys Arg Leu 145 150 155 160 Ser Leu Ala Phe Lys His Gin Lys Thr Lys Ile Pro His Tyr Ile Leu 165 170 175 Lys Glu Ala Ala Leu Lys Thr Asn Leu Lys Arg Gin Asp Ile Leu Asn 180 185 190 Tyr Leu Gin Lys Ile Tyr Tyr Thr Leu Gly Lys Lys Glu Gin Ser Gly 195 200 205 Leu Lys Ala Phe Tyr Arg Glu Leu Leu Phe Lys Arg Ile Gin Lys Pro 210 215 220 Lys Arg Phe 225 INFORMATION FOR SEQ ID NO:125: SEQUENCE CHARACTERISTICS: LENGTH: 305 amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...305 (xi) SEQUENCE DE.C'.IPTION: SEQ ID NO:125: Met Gly Arg Ile Glu Ser Lys Lys Arg Leu Lys Ala Leu Ile Phe Leu 1 5 10 Ala Ser Leu Gly Val Leu Trp Gly Asn Ala Ala Glu Lys Thr Pro Phe 25 Phe Lys Thr Lys Asn His Ile Tyr Leu Gly Phe Arg Leu Gly Thr Gly 40 Ala Thr Thr Arg Thr Ser Met Trp Gin Gin Ala Tyr Lys Asp Asn Pro WO 98/24475 PCT/US97/22104 -208- 55 Thr Cys Pro Ser Ser Val Cys Tyr Gly Glu Lys Leu Glu Ala His Tyr 70 75 Lys Gly Gly Lys Asn Leu Ser Tyr Thr Gly Gin Ile Gly Asp Glu Ile 85 90 Ala Phe Asp Lys Tyr His Ile Leu Gly Leu Arg Val Trp Gly Asp Val 100 105 110 Glu Tyr Ala Lys Ala Gin Leu Gly Gin Lys Val Gly Gly Asn Thr Leu 115 120 125 Leu Ser Gin Ala Asn Tyr Asn Pro Ser Ala Ile Lys Thr Tyr Asp Pro 130 135 140 Thr Ser Asn Ala Gin Gly Ser Leu Val Leu Gin Lys Thr Pro Ser Pro 145 150 155 160 Gin Asp Phe Leu Phe Asn Asn Gly His Phe Met Ala Phe Gly Leu Asn 165 170 175 Val Asn Met Phe Val Asn Leu Pro Ile Asp Thr Leu Leu Lys Leu Ala 180 185 190 Leu Lys Thr Glu Lys Met Leu Phe Phe Lys Ile Gly Val Phe Gly Gly 195 200 205 Gly Gly Val Glu Tyr Ala Ile Leu Trp Ser Pro Gin Tyr Lys Asn Gin 210 215 220 Asn Thr His Gin Asp Asp Lys Phe Phe Ala Ala Gly Gly Gly Phe Phe 225 230 235 240 Val Asn Phe Gly Gly Ser Leu Tyr Ile Gly Lys Arg Asn Arg Phe Asn 245 250 255 Val Gly Leu Lys Ile Pro Tyr Tyr Ser Leu Ser Ala Gin Ser Trp Lys 260 265 270 Asn Phe Gly Ser Ser Asn Val Trp Gin Gin Gin Thr Ile Arg Gin Asn 275 280 285 Phe Ser Val Phe Arg Asn Lys Glu Val Phe Val Ser Tyr Ala Phe Leu 290 295 300 Phe 305 INFORMATION FOR SEQ ID NO:126: SEQUENCE CHARACTERISTICS: LENGTH: 258 amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: miscfeature LOCATION 1...258 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:126: WO 98/24475 PCTfS97/22104 -209- Met Phe Leu Arg Ser Tyr Pro Lys Leu Arg Tyr Ala Leu Cys Leu Pro 1 5 10 Leu Thr Thr Phe 65 Gin Val Thr Ala Met 145 Ala Thr Tyr Lys Ser 225 Arg Arg Leu Thr Ser Arg Lys Asp Val Ala 130 Glu Ala Phe Thr Asn 210 Glu Asp Leu Thr Gin Lys Thr Ile Gly Ile 115 Asn Thr Ser Arg His 195 Leu Gin Thr Glu Ala Glu Asn Tyr Ala 100 Asp Ala Lys Gly Ser 180 Gin Phe Asn Leu Thr Lys Leu Pro Val Ala Pro Ser Gly Ala 165 Ala Asn Lys Asn Thr 245 Cys Arg Asp Asp 70 Arg Gin Gly Ala Ala 150 Val Tyr Ile Pro Ala 230 Phe Tyr Ile Gin 55 Val Gly Asn Met Gly 135 Ala Ser Gin Phe Thr 215 Leu Ser Phe Arg Asn Ile Gly Leu 120 Pro Asp Phe Ser Tyr 200 Gin Ile Glu 25 Thr Gin Val Glu Asn 105 Lys Gly Phe Tyr Ala 185 Tyr Ala Lys Glu Tyr Ser Gly Asp 90 Ile Ser Ala Ile Thr 170 His Arg Asp Met Arg Asn Asn Gly 75 Arg Tyr Val Ile Pro 155 Asn Phe Ser Lys Asn 235 Thr Asn Glu Gly Leu His Glu Ala 140 Arg Phe Asp Gly Glu 220 Gly Asn Phe Lys Val Arg Gin 110 Thr Val Lys Asp Ile 190 Thr Gly Leu Lys Lys Asp Met Val Gly Lys Ile Asn Arg 175 Ala Val Thr Ser Val Val Leu Gly Thr Asn Gly Lys Tyr 160 Glu Tyr Met Pro Asp 240 Ser Trp Asn Met Thr Arg Asp Asn 250 Ala Thr 255 INFORMATION FOR SEQ ID NO:127: SEQUENCE CHARACTERISTICS: LENGTH: 192 amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...192 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:127: WO 98/24475 PCT/US97/22104 -210- Met Phe Leu Arg Ser Tyr Pro Lys Leu Arg Tyr Ala Leu Cys Leu Pro 1 5 10 Leu Leu Thr Glu Thr Cys Tyr Ser Glu Glu Arg Thr Leu Asn Lys Val 20 25 Thr Thr Gin Ala Lys Arg Ile Phe Thr Tyr Asn Asn Glu Phe Lys Val 40 Thr Ser Lys Glu Leu Asp Gin Arg Gin Ser Asn Glu Val Lys Asp Leu 55 Phe Arg Thr Asn Pro Asp Val Asn Val Gly Gly Gly Ser Val Met Gly 70 75 Gin Lys Ile Tyr Val Arg Gly Ile Glu Asp Arg Leu Leu Arg Val Thr 90 Val Asp Gly Ala Ala Gin Asn Gly Asn Ile Tyr His His Gin Gly Asn 100 105 110 Thr Val Ile Asp Pro Gly Met Leu Lys Ser Val Glu Val Thr Lys Gly 115 120 125 Ala Ala Asn Ala Ser Ala Gly Pro Gly Ala Ile Ala Gly Val Ile Lys 130 135 140 Met Glu Thr Lys Gly Ala Ala Asp Phe Ile Pro Arg Gly Lys Asn Tyr 145 150 155 160 Ala Ala Ser Gly Ala Val Ser Phe Tyr Thr Asn Phe Gly Asp Arg Glu 165 170 175 Thr Phe Arg Ser Ala Tyr Gin Ser Ala His Phe Asp Ile Ile Ala Tyr 180 185 190 INFORMATION FOR SEQ ID NO:128: SEQUENCE CHARACTERISTICS: LENGTH: 126 amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...126 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:128: Val Pro Leu Ser Leu Gly Gly Asn Leu Leu Asn Pro Asn Asn Ser Ser 1 5 10 Val Leu Asn Leu Lys Asn Ser Gin Leu Val Phe Ser Asp Gin Gly Ser 20 25 Leu Asn Ile Ala Asn Ile Asp Leu Leu Ser Asp Leu Asn Gly Asn Lys 40 Asn Arg Val Tyr Asn Ile Ile Gin Ala Asp Met Asn Gly Asn Trp Tyr 55 WO 98/24475 PCTIUS97/22104 -211- Glu Arg Ile Asn Phe Phe Gly Met Arg Ile Asn Asp Gly Ile Tyr Asp 70 75 Ala Lys Asn Gin Thr Tyr Ser Phe Thr Asn Pro Leu Asn Asn Ala Val 90 Lys Phe Thr Glu Ser Phe Phe Ile His Arg Leu Cys Gly Ser Leu Ser 100 105 110 Gin Ile Gin Lys Lys Lys Asn Thr Ile Val Ser Pro Arg Leu 115 120 125 INFORMATION FOR SEQ ID NO:129: SEQUENCE CHARACTERISTICS: LENGTH: 565 amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: miscfeature LOCATION 1...565 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:129: Val Tyr Ser Tyr Ser Asp Asp Ala Gin Gly Val Phe Tyr Leu Thr Ser 1 5 10 Ser Val Lys Gly Tyr Tyr Asn Pro Asn Gin Ser Tyr Gin Ala Ser Gly 25 Ser Asn Asn Thr Thr Lys Asn Asn Asn Leu Thr Ser Glu Ser Ser Val 35 40 Ile Ser Gin Thr Tyr Asn Ala Gin Gly Asn Pro Ile Ser Ala Leu His 55 Val Tyr Asn Lys Gly Tyr Asn Phe Ser Asn Ile Lys Ala Leu Gly Gin 70 75 Met Ala Leu Lys Leu Tyr Pro Glu Ile Lys Lys Ile Leu Gly Asn Asp 90 Phe Ser Leu Ser Ser Leu Ser Asn Leu Lys Gly Asp Ala Leu Asn Gin 100 105 110 Leu Thr Lys Leu Ile Thr Pro Ser Asp Trp Lys Asn Ile Asn Glu Leu 115 320 125 Ile Asp Asn Ala Asn Asn Se&' Val Val Gin Asn Phe Asn Asn Gly Thr 130 135 140 Leu Ile Ile Gly Ala Thr Lys Ile Gly Gin Thr Asp Thr Asn Ser Ala 145 150 155 160 Val Val Phe Gly Gly Leu Gly Tyr Gin Lys Pro Cys Asp Tyr Thr Asp 165 170 175 Ile Val Cys Gin Lys Phe Arg Gly Thr Tyr Leu Gly Gin Leu Leu Glu 180 185 190 Ser Asn Ser Ala Asp Leu Gly Tyr Ile Asp Thr Thr Phe Asn Ala Lys WO 98/24475 PTU9/20 PCTIUS97/22104 -2 12- 195 200 Giu Ile Tyr Leu Thr Gly Thr Leu Gly 225 Asn Leu Asn Leu Gly 305 Giy Ala Vai Lys Leu 385 Val Lys Giy Ile Ile 465 Gly Phe Ser Ile Leu 545 210 Gly Gin Giy Ile Gly 290 Tyr Gin Ile Gly Leu 370 Phe Ile Asn Gin Lys 450 Tyr Ile Ser Asn Phe 530 Asn Ala Ser Ala Gin Leu 275 Asn Leu Asn Lys Giy 355 Ile Asn Ser Asp Asp 435 Ser Giu Phe Phe Aila 515 Aia Leu Aila Aia Asn Giu 260 Gly Leu Thr Asn Asp 340 Leu Giy Gin Vai Vai 420 Thr Vai Gin Aia Asn 500 Asn Giy Leu Thr Ser Ile 245 Giy Giu Ile Pro Phe 325 Leu Aia Ser Ile Met 405 Aia Leu Leu Gly Pro 485 Ala Giy Asn Ser Aia 565 Val 230 Val Ile Val Val Giu 310 Asp Ile Gly Met Thr 390 Leu Ala Asn Asp Leu 470 Tyr Gin Gly Asn Asn 550 215 Thr Ser Asn Ala Asn 295 Gin Asn Arg Leu Ser 375 Gly Gin Leu Ser Lys 455 Gly Gly Giy Thr His 535 Gin Phe Ser Lys Met 280 Thr Lys Leu Gin Gly 360 Ile Phe Asp Gly Leu 440 Val Asp Leu Asn Leu 520 Ile Val Giy Asn Gin Val 265 Gin Leu Asn Met Lys 345 Gly Asn.

Ile Ile Lys 425 Glu Leu Leu Ser Val 505 Ser Aila Ser Ser Ser Thr 250 Phe Ser Gly Gin Asn 330 Leu Ile Asp Ser Val 410 Gin Ser Ala Ile Gin 490 Phe Phe Phe Asn Gly Gin 235 Asp Asn Ile Ser Thr 315 Asp Gly Asp Leu Aila 395 Lys Met Leu Al a Pro 475 Val Val Asn Thr Ile 555 Trp Leu Phe Gly 270 Ala Val Gin Leu Thr 350 Asn Lys Ile Asp Giu 430 Asn Leu Gly Lys Ser 510 Asn Ser Thr Gly Ile Ser 255 Leu Giy Ile Leu Asn 335 Giy Pro Lys Gly Ala 415 Phe Gin Giy Lys Gly 495 Thr Ser Giy Met Thr Leu 240 Met Ala Giy Giy Leu 320 Thr Leu Giu Gly Gin 400 Leu Leu Gin Ser Lys 480 Asp Phe Leu Thr Leu 560 INFORMATION FOR SEQ ID SEQUENCE CHARACTERISTICS: LENGTH: 172 amino acids TYPE: amino acid TOPOLOGY: linear WO 98/24475 PCTIUS97/22104 -213- (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: miscfeature LOCATION 1...172 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:130: Val Phe Gly Leu Ser Leu Ala Asp Met Ile Leu Glu Arg Phe Lys Asp 1 5 10 Phe Met Arg Glu Tyr Pro Glu Pro Tyr Lys Phe Leu Gin Val Phe Tyr 25 Ala Gin Glu Lys Glu Arg Phe Leu Asn His Lys Met Asn Asp Tyr Ile 35 40 Lys Gin Asn Lys Ser Lys Glu Glu Ala Ser Ile Leu Ala Arg Gin Gly 55 Phe Val Ser Val Ile Gly Arg Ala Leu Glu Lys Ile Ile Glu Leu Leu 70 75 Leu Lys Asp Phe Cys Ile Lys Asn Asn Val Lys Met Thr Asn Asp Lys 90 Thr Leu Arg Ala Lys Arg Ile Asn Gly Glu Leu Asp Lys Val Lys Arg 100 105 110 Ala Leu Leu Val His Phe Gly Gly Tyr Ser Val Leu Pro Asp Ile Ile 115 120 125 Leu Tyr Gin Thr Asn Lys Asp Asn Ile Lys Ile Leu Ala Ile Leu Ser 130 135 140 Val Lys Asn Ser Phe Arg Glu Arg Phe Thr Lys Asp Ala Leu Leu Glu 145 150 155 160 Ile Lys Thr Phe Ala Ile Ala Cys Asn Phe Ser His 165 170 INFORMATION FOR SEQ ID NO:131: SEQUENCE CHARACTERISTICS: LENGTH: 331 amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...331 WO 98/24475 -214- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:i31: Met Lys Arg Phe Val Leu Phe Leu Leu Phe Ile Cys PCTIUJS97/22104 Val Ile Ile Gly Met Pro Leu Met Ser 145 Ser Ser Asn Ile Pro 225 Ala Trp Ala Leu Tyr 305 Glu Gin Asp Gin Val1 Val1 Tyr Gin Pro 130 Pro Ala Ser Arg Ala 210 Thr Ile Gly Thr Ile 290 Ser Asp Ala Leu Pro Arg Ser Gly Ser 115 Tyr Giu Leu Ala Trp 195 Ser Lys Thr Ser Trp 275 Gly Ser Gly Tyr Pro Cys Giu Tyr Leu 100 Val Met Tyr Asn Leu 180 Gin Ala Gly Ile Gly 260 Ile Val Pro Phe Al a Gin Ala Pro Asp 85 Lys Asp Asn Giu Thr 165 Ala Giu lI*e Ile Ser 245 Ala Leu His Ser Arg 325 Giu Lys Gin Asp 70 Leu Ala Thr Met Asp 150 Asn Leu Trp Thr Lys 230 Gly Gly Asn Asn Ala 310 Leu Gin Leu Leu 55 Ala Ala Ile Tyr Ala 135 Phe His Asp Val Arg 215 Gly Giu Gin Pro Asn 295 Asp Lys Asp Tyr 25 His Leu 40 Asn Ala Cys Thr Leu Gly Glu Ile 105 Gin Ser 120 Tyr Trp Ilie Arg Gly Ala Asp His 185 Phe Lys 200 Ser Asp Ilie Ala Leu Leu Arg Leu 265 Giu Thr 280 Ala Tyr Giu Leu Leu Arg 10 Phe Asp Ser Lys Tyr 90 Leu Glu Phe Arg Trp 170 Ala Ala Thr Tyr Phe 250 S er Phe Phe Leu Ser 330 Phe Lys Lys Ser 75 Leu Asn Asp Val Met 155 Gly Leu Ile Ser Thr 235 Glu Val Pro Ile Glu 315 Pro Arg Lys His Phe Val Ala Asn Lys 140 Arg Ile Leu Asp Asp 220 Asn Asn Al a Tyr Ile 300 Gin Val Asp Leu Tyr Lys Ser Trp Ile 125 Lys Gin Leu Gin Glu 205 Tyr Phe Gly Tyr Phe 285 Leu Gly Cys Phe Ser Thr Lys Gin Ala 110 Asn Glu Tyr Phe Ser 190 Asn His Ala Tyr Asn 270 Gin Ala Asp Val Lys Gin Ala Ser Asn Asn Phe Phe Ser Asp 175 Ser Gly Gly Leu Asp 255 Lys Pro Lys Leu Cys Ser Thr Thr Al a Lys Glu Tyr Pro Gin 160 Val Ala Vai Gly Leu 240 Leu Al a Asn His His 320 INFORMATION FOR SEQ ID NO:132: SEQUENCE CHARACTERISTICS: LENGTH: 128 amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein WO 98/24475 PCTfUS97/22104 -215- (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...128 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:132: Met Arg Gin Tyr Ser Gin Ser Ala Leu Asn Thr Asn His Gly Ala Trp 1 5 10 Gly Ile Leu Phe Asp Val Ser Ser Ala Leu Ala Leu Asp Asp His Ala 25 Leu Leu Gin Ser Ser Ala Asn Arg Trp Gin Glu Trp Val Phe Lys Ala 40 Ile Asp Glu Asn Gly Val Ile Ala Ser Ala Ile Thr Arg Ser Asp Thr 50 55 Ser Asp Tyr His Gly Gly Pro Thr Lys Gly Ile Lys Gly Ile Ala Tyr 70 75 Thr Asn Phe Ala Leu Leu Ala Ile Thr Ile Ser Gly Glu Leu Leu Phe 90 Glu Asn Gly Tyr Asp Leu Trp Gly Ser Gly Ala Gly Gin Arg Leu Ser 100 105 110 Val Ala Tyr Asn Lys Ala Ala Thr Trp Ile Leu Asn Pro Glu Thr Phe 115 120 125 INFORMATION FOR SEQ ID NO:133: SEQUENCE CHARACTERISTICS: LENGTH: 245 amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCA-I'N 1...245 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:133: Leu Arg Thr Leu Leu Lys Met Leu Val Gly Val Ser Leu Leu Thr His 1 5 10 Ala Leu Met Ala Thr Glu Glu Ser Ala Ala Pro Ser Trp Thr Lys Asn 25 Leu Tyr Met Gly Phe Asn Tyr Gin Thr Gly Ser Ile Asn Leu Met Thr WO 98/24475 PCTIU)S97/22104 -216- 40 Asn Ile His Glu Val Arg Glu Val Thr Ser Tyr Gin Thr Gly Tyr Thr 55 Asn Val Met Thr Ser Ile Asn Ser Val Lys Lys Leu Thr Asn Met Gly 65 70 75 Ser Asn Gly Ile Gly Leu Val Met Gly Tyr Asn His Phe Phe His Pro 90 Asp Lys Val Leu Gly Leu Arg Tyr Phe Ala Phe Leu Asp Trp Gin Gly 100 105 110 Tyr Gly Met Arg Tyr Pro Lys Gly Tyr Tyr Gly Gly Asn Asn Met Ile 115 120 125 Thr Tyr Gly Val Gly Val Asp Ala Ile Trp Asn Phe Phe Gin Gly Ser 130 135 140 Phe Tyr Gin Asp Asp Ile Gly Val Asp Ile Gly Val Phe Gly Gly Ile 145 150 155 160 Ala Ile Ala Gly Asn Ser Trp Tyr Ile Gly Asn Lys Gly Gin Glu Leu 165 170 175 Leu Gly Ile Thr Asn Ser Ser.Ala Val Asp Asn Thr Ser Phe Gin Phe 180 185 190 Leu Phe Asn Phe Gly Phe Lys Ala Leu Phe Val Asp Glu His Glu Phe 195 200 205 Glu Ile Gly Phe Lys Phe Pro Thr Leu Asn Asn Lys Tyr Tyr Thr Thr 210 215 220 Asp Ala Leu Lys Val Gin Met Arg Arg Val Phe Ala Phe Tyr Val Gly 225 230 235 240 Tyr Asn Tyr His Phe 245 INFORMATION FOR SEQ ID NO:134: SEQUENCE CHARACTERISTICS: LENGTH: 290 amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: miscfeature LOCATION 1...290 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:134: Met Phe Glu Glu Ile Thr Leu Ala His Lys Asp Leu Phe Ser Arg Phe 1 5 10 Leu Gin Thr Gin Lys Ile Val Leu Ser Asp Val Ser Phe Thr Asn Cys 25 Phe Leu Trp Gin His Ala Arg Leu Ile Gin Val Ala Val Ile Arg Asp 40 WO 98/24475 PCTfUS97/22104 -217- Cys Leu Val Ile Gin Thr Thr Tyr Glu Asn Gin Lys Pro Phe Tyr Phe 55 Tyr Pro Ile Gly Lys Arg Pro His Glu Cys Val Lys Glu Leu Leu Glu 70 75 Leu Glu Lys Asn Leu Arg Phe His Ser Leu Thr Leu Glu Gin Lys Asp 90 Asp Leu Lys Asp Asn Phe Val Gly Val Phe Asp Phe Thr Tyr Asn Arg 100 105 110 Asp Arg Ser Asp Tyr Val Tyr Ser Ile Glu Glu Leu Ile Ala Leu Lys 115 120 125 Gly Lys Lys Tyr His Lys Lys Lys Asn His Leu Asn Gin Phe Leu Thr 130 135 140 Asn His Ala Asn Phe Val Tyr Glu Lys Ile Ser Pro Gin Asn Arg Lys 145 150 155 160 Glu Val Leu Glu Ala Ser Lys Ala Trp Phe Leu Glu Ser Gin Thr Asp 165 170 175 Asp Ile Gly Leu Ile Asn Glu Asn Lys Gly Ile Gin Ser Val Leu Glu 180 185 190 Asn Tyr Glu Ser Leu Asp Leu Lys Gly Gly Leu Ile Arg Val Asn Gly 195 200 205 Glu Ile Val Ser Phe Ser Phe Gly Glu Val Leu Asn Glu Glu Ser Ala 210 215 220 Leu Ile His Ile Glu Lys Ala Arg Thr Asp Ile Ala Gly Ala Tyr Gin 225 230 235 240 Ile Ile Asn Gin Gin Leu Leu Leu Asn Glu Phe Ser His Leu Thr Tyr 245 250 255 Ala Asn Arg Glu Glu Asp Leu Gly Leu Glu Gly Leu Arg Arg Ser Lys 260 265 270 Met Ser Tyr Asn Pro Val Phe Leu Ile Asp Lys Tyr Glu Ala Val Ala 275 280 285 Arg Asn 290 INFORMATION FOR SEQ ID NO:135: SEQUENCE CHARACTERISTICS: LENGTH: 110 amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...110 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:135: Met Met Phe Ile Val Ala Val Leu Met Leu Ala Phe Leu Ile Phe Val WO 98/24475 PCT/US97/22104 -218- 1 5 10 His Glu Leu Gly His Phe Ile Ile Ala Arg Ile Cys Gly Val Lys Val 25 Glu Val Phe Ser Ile Gly Phe Gly Lys Lys Leu Trp Phe Phe Lys Leu 35 40 Phe Gly Thr Gin Phe Ala Leu Ser Leu Ile Pro Leu Gly Gly Tyr Val 55 Lys Leu Lys Gly Met Asp Lys Glu Glu Asn Glu Glu Asn Lys Ile Asn 70 75 Gin Ala Asn Asp Ser Tyr Ala Lys Lys Ala Leu Ser Lys Ser Tyr Gly 90 Tyr Cys Leu Val Gly Arg Phe Leu Ile Phe Phe Leu Arg Phe 100 105 110 INFORMATION FOR SEQ ID NO:136: SEQUENCE CHARACTERISTICS: LENGTH: 351 amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...351 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:136: Met Met Phe Ile Val Ala Val Leu Met Leu Ala Phe Leu Ile Phe Val 1 5 10 His Glu Leu Gly His Phe Ile Ile Ala Arg Ile Cys Gly Val Lys Val 25 Glu Val Phe Ser Ile Gly Phe Gly Lys Lys Leu Trp Phe Phe Lys Leu 35 40 Phe Gly Thr Gin Phe Ala Leu Ser Leu Ile Pro Leu Gly Gly Tyr Val 55 Lys Leu Lys Gly Met Asp Lys Glu Glu Asn Glu Glu Asn Lys Ile Asn 70 75 Gin Ala Asn Asp Ser Tyr Ala Gin Lys Se- Pro Phe Gin Lys Leu Trp 3 Ile Leu Phe Gly Gly Ala Phe Phe Asn Phe Leu Phe Ala Val Leu Val 100 105 110 Tyr Phe Phe Leu Ala Leu Ser Gly Glu Lys Val Leu Leu Pro Val Ile 115 120 125 Gly Gly Leu Glu Lys Asn Ala Leu Glu Ala Gly Leu Leu Lys Gly Asp 130 135 140 Arg Ile Leu Ser Ile Asn His Gin Lys Ile Ala Ser Phe Arg Glu Ile 145 150 155 160 WO 98/24475 PCT/US97/22104 -219- Arg Arg Val Ile Val 225 Val Val Ala Asn Gin 305 Thr Phe Glu Asn Ile Gly 210 Phe Leu Lys Asn Leu 290 Met Pro Val Ile Asn Ser 195 Ile Gin Ile Glu Ser 275 Gly Leu Ile Met Val Gin 180 Glu Lys Ala Val Leu 260 Val Ile Gly Gin Phe 340 Ala 165 Ile Ser Pro Phe Asp 245 Ser Ser Leu Val Asn 325 Leu Arg Leu Asn Asp Glu 230 Ser Gly Met Asn Val 310 Ala Gly Gin Lys Pro 200 Gin Ala Arg Ile Leu 280 Leu Lys Trp Phe Gly Glu 170 Arg Leu 185 Asn Glu Lys Met Leu Ser Arg Leu 250 Gly Ile 265 Leu Phe Pro Ile Asn Ile Leu Val 330 Asn Asp 345 Leu Thr Ile Gly Arg 235 Ile Val Gly Pro Phe 315 Gly Ile Pro Ile Val 220 Phe Met Gly Ala Ala 300 His Val Glu Ile 190 Tyr Ser Glu Ser Leu 270 Leu Asp Ala Phe Ile 175 Val Lys Tyr Gly Ala 255 Ser Ser Gly Leu Leu Glu Ala Ile Ser Val 240 Ser His Ile Ala Pro 320 Val Ile Thr Arg 335 Leu Leu 350 INFORMATION FOR SEQ ID NO:137: SEQUENCE CHARACTERISTICS: LENGTH: 100 amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: miscfeature LOCATION 1...100 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:137: Met Gin Ly. 1.sn Leu Asp Ser Leu Leu Glu Asn Leu Arg Ala Glu Ile 1 5 10 Asp Ala Leu Asp Asn Glu Leu Ser Asp Leu Leu Asp Lys Arg Leu Gly 25 Ile Ala Leu Lys Ile Ala Leu Ile Lys Gin Glu Ser Pro Gin Glu Asn 40 Pro Ile Tyr Cys Pro Lys Arg Glu Gin Glu Ile Leu Lys Arg Leu Ser 55 Gin Arg Gly Phe Lys His Leu Asn Gly Glu Ile Leu Ala Ser Phe Tyr WO 98/24475 PCT/US97/22104 -220- 70 75 Ala Glu Val Phe Lys Ile Ser Arg Asn Phe Gin Glu Asn Ala Leu Lys 90 Glu Leu Lys Lys 100 INFORMATION FOR SEQ ID NO:138: SEQUENCE CHARACTERISTICS: LENGTH: 174 amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc_feature LOCATION 1...174 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:138: Val Lys Met Arg Phe Phe Ser Gly Phe Gly Phe Val Asn Glu Ser Val 1 5 10 Leu Phe Glu Glu Trp Leu Leu Lys Gly Ala Tyr Asp Val Ser Gly Phe 20 25 Ser Met Gly Ala Ile Lys Ala Ile Glu Tyr Ala Tyr Asn Glu Val Leu 40 Gin Gin Arg Arg Ile His Ser Leu Leu Leu Phe Ser Pro Cys Met Leu 55 Ala His Lys Ser Leu Ala Phe Lys Arg Leu Gin Leu Phe Leu Phe Gln 70 75 Lys Asp Pro Gin Ser Tyr Met Asp Asn Phe Tyr Lys Glu Val Gly Leu 90 Asp Ala Gin Leu Glu Arg Phe Lys Lys Glu Gly Ser Leu Glu Glu Leu 100 105 110 Glu Phe Leu Leu Asp Tyr Lys Tyr Ser Asp Ser Ile Ile Arg Phe Leu 115 120 125 Leu Glu Lys Gly Val Lys Ile Glu Val Phe Ile Gly Leu Lys Asp Arg 130 135 140 Ile Thr Asp Ile Gin Ala Leu Leu Glu Phe Phe Met Pro Leu Val Gin 145 150 155 160 Val Trp Gin Phe Lys Asp Cys Asn His Leu Leu Gln Lys Ser 165 170 INFORMATION FOR SEQ ID NO:139: SEQUENCE CHARACTERISTICS: LENGTH: 471 amino acids TYPE: amino acid WO 98/24475 PTU9/20 PCTIUS97/22104 -221 TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc-feature LOCATION .471 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:139: Met Lys Asn Thr Asn Thn Lys Giu Ile Lys Asn Thr 1 Gly Leu Phe Asn 65 Gin Thr Asn Lys Al a 145 Asn Glu Sen Val Met 225 Giu Lys Leu Gly Gin Tyr Leu Tyn Asn Val Asn Thn Lys 130 Tyn Leu Tyr Leu Asn 210 Gin Asn Thn Gly Pro 290 Val Gin Ser Gly Gly Val Thn 100 Thr Leu Val Asn Gly 180 Ala Asp Phe Lys Sen 260 Met Thr Tyr His Pro Gly Thr 70 Met Asp Val Gin Ala 150 Sen Ile Glu Asn Asp 230 Gly Arg Lys Sen Gin Thn Leu Tyr Leu Ala Ala Gly Ile 135 Leu Asn Lys Ser Ser 215 Thr Gly Ile Asn Gin 295 Phe Leu Ser Gin Arg Gly Leu Asn 120 Glu Gin Asn Val Val 200 Val Sen Al a Ala Tyr 280 His Phe Lys 25 Val Ile Asn Gly Leu 105 Asn Gin Vai Giy Leu 185 Ala Phe Ser Gly Thr 265 Asp Giy Gly 10 Lys Ala Gly Asn Asn Gly Asn Arg Tyr Ser 170 Tyn Leu Leu Al a Al a 250 Tyr Glu Val Ser Gly Leu Gly Val 75 Gly Ile Ala Phe Leu 155 Asn Gly Leu Lys Lys 235 Met Gin Pro Ile Lys Arg Leu Giu Gin Asp Leu Asn Leu 125 Thr Asn Gly Gin Ala 205 Leu Gly Gin Asn Leu 285 Gly Asn Met Lys Asp Gin Asp Ala Gin Thn Asn Val Val Asn 190 Leu Leu Gin Leu 270 Pro Phe Ile Lys Thr Asp Asn Phe Leu Ile Gin Lys Leu Val1 175 Glu Thr Ala Ile Asp 255 Lys Gin Gly Gly Lys Ala Gly Ile Arg Ala Val Phe Asn Tyr 160 Pro Phe Arg Gin Ala 240 Val Gin Phe Ile Leu WO 98/24475 PCTIUS97/22104 -222- 305 310 315 320 Arg Tyr Tyr Ala Phe Phe Asp Tyr Gly Phe Thr Gin Leu Gly Ser Leu 325 330 335 Asn Ser Ala Val Lys Ala Asn Ile Phe Thr Tyr Gly Ala Gly Thr Asp 340 345 350 Phe Leu Trp Asn Ile Phe Arg Arg Val Phe Ser Asp Gin Ser Leu Asn 355 360 365 Val Gly Val Phe Gly Gly Ile Gin Ile Ala Gly Asn Thr Trp Asp Ser 370 375 380 Ser Leu Arg Gly Gin Ile Glu Asn Ser Phe Lys Glu Tyr Pro Thr Pro 385 390 395 400 Thr Asn Phe Gin Phe Leu Phe Asn Leu Gly Leu Arg Ala His Phe Ala 405 410 415 Ser Thr Met His Arg Arg Phe Leu Ser Ala Ser Gin Ser Ile Gin His 420 425 430 Gly Met Glu Phe Gly Val Lys Ile Pro Ala Ile Asn Gin Arg Tyr Leu 435 440 445 Lys Ala Asn Gly Ala Asp Val Asp Tyr Arg Arg Leu Tyr Ala Phe Tyr 450 455 460 Ile Asn Tyr Thr Ile Gly Phe 465 470 INFORMATION FOR SEQ ID NO:140: SEQUENCE CHARACTERISTICS: LENGTH: 129 amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...129 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:140: Met Lys Ser Ile Arg Arg Gly Asp Gly Leu Asn Val Val Pro Phe Ile 1 5 10 Asp Ile Met Leu Val Leu Leu AlI Ile Val Leu Ser Ile Ser Thr Phe 25 Ile Ala Gin Gly Lys Ile Lys Val Ser Leu Pro Asn Ala Lys Asn Ala 40 Glu Lys Ser Gin Pro Asn Asp Gin Lys Val Val Val Ile Ser Val Asp 50 55 Glu His Asp Asn Ile Phe Val Asp Asp Lys Pro Thr Asn Leu Glu Ala 70 75 Leu Ser Ala Val Val Lys Gin Thr Asp Pro Lys Thr Leu Ile Asp Leu 90 WO 98/24475 PCT/US97/22104 -223- Lys Ser Asp Lys Ser Ser Arg Phe Glu Thr Phe Ile Ser Ile Met Asp 100 105 110 Ile Leu Lys Glu His Asn His Glu Asn Phe Ser Ile Ser Thr Gin Ala 115 120 125 Gin INFORMATION FOR SEQ ID NO:141: SEQUENCE CHARACTERISTICS: LENGTH: 75 amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...75 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:141: Met Leu Val Leu Leu Ala Ile Val Leu Ser Ile Ser Thr Phe Ile Ala 1 5 10 Gin Gly Lys Ile Lys Val Ser Leu Pro Asn Ala Lys Asn Ala Glu Lys 25 Ser Arg Pro Asn Asp Gin Lys Val Val Val Ile Ser Val Asp Glu His 40 Asp Asn Ile Phe Val Asp Asp Lys Pro Thr Asn Leu Glu Ala Leu Ser so 55 Ala Val Val Lys Gin Thr Asp Pro Lys Thr Leu 70 INFORMATION FOR SEQ ID NO:142: SEQUENCE CHARACTERISTICS: LENGTH: 223 amino acids TYPE: amino acid TOPOLOGY: linear 'ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc_feature WO 98/24475 PTU9/20 PCT/US97/22104 224 LOCATION .223 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:142: met Phe Ser Leu Ser Tyr Val. Ser Lys Lys Phe Leu 1 Leu Leu Asn Asp Leu Lys Phe Lys Thr 145 Val Met Lys Ala Ile Asp Asp Val Leu Asp Ser Val 130 Giu Leu Pro Tyr Tyr 210 Ser Glu 35 Lys Phe Val Leu Ala Gly Glu Ser Ser Gin 195 Ile 5 Phe Leu Asp Asp Giy Asn Tyr Lys Al a Lys 165 Gin Thr Tyr Leu Leu Asn Asn 70 Arg Val Vai Asp Gin 150 Thr Phe Lys Lys Ser Ser Ile 55 Lys Asn Lys Asn Lys 135 Ile Gly Leu Asn Thr 215 Ala Ser Asp Ser Gly Giu Ile 120 Asn Tyr Lys Ala Asp 200 Asn Cys Gly Lys Ile Cys Leu 105 Ser Asp Ala Thr Val 185 Giu Leu 10 Lys Thr Lys Ser Ser 90 Arg Tyr Glu Val Ile 170 Leu Asp Ser Ser Gin Ser Pro 75 Tyr Asn Ser Lys Gin 155 Tyr Glu Leu Lys Asn Ser Tyr Asn Cys Tyr Lys Glu 140 Ser Giu Phe Thr Ser 220 Val Lys Lys Giy Lys Arg Lys 110 His Lys Pro Pro Gly 190 Lys Ser Leu Asp Giu Leu Tyr Leu Glu Asn Met Thr Gly 175 Asp Leu Ser Leu Lys Leu Glu Met Lys His Phe Ser Ile 160 Tyr Gly Lys INFORMATION FOR SEQ ID NO:143: Wi SEQUENCE CHARACTERISTICS: LENGTH: 116 amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pyloni (ix) FEATURE: NAME/KEY: misc feature LOCATION .116 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:i43: Leu Met Lys Ser Lys Ile Thr His Phe Ile Val Ile Ser Phe Val. Leu WO 98/24475 PCT/US97/22104 -225- 1 5 10 Ser Val Leu Ser Ala Cys Lys Asp Glu Pro Lys Lys Ser Ser Gin Ser 25 His Gin Asn Asn Thr Lys Thr Thr Gin Asn Asn Gin Ile Asn Gin Pro 35 40 Asn Lys Asp Ile Lys Lys Ile Glu His Glu Glu Glu Asp Glu Lys Val 55 Thr Lys Glu Val Asn Asp Leu Ile Asn Asn Glu Asn Lys Ile Asp Glu 70 75 Ile Asn Asn Glu Glu Asn Ala Asp Pro Ser Gin Lys Arg Thr Asn Asn 90 Val Leu Gin Arg Ala Thr Asn His Gin Asp Asn Leu Ser Ser Pro Leu 100 105 110 Asn Arg Lys Tyr 115 INFORMATION FOR SEQ ID NO:144: SEQUENCE CHARACTERISTICS: LENGTH: 79 amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...79 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:144: Met Phe Glu Lys Ile Arg Lys Ile Leu Ala Asp Ile Glu Asp Ser Gin 1 5 10 Asn Glu Ile Glu Met Leu Leu Lys Leu Ala Asn Leu Ser Leu Gly Asp 20 25 Phe Ile Glu Ile Lys Arg Gly Ser Met Asp Met Pro Lys Gly Val Asn 40 Glu Ala Phe Phe Thr Gin Leu Ser Glu Glu Val Glu Arg Leu Lys Glu 55 Leu Ile Asn Ala Leu Asn Lys Ile Lys Lys Gly Lev Leu Val Phe 70 INFORMATION FOR SEQ ID NO:145: SEQUENCE CHARACTERISTICS: LENGTH: 51 amino acids TYPE: amino acid TOPOLOGY: linear WO 98/24475 PCTIUS97/22104 -226- (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...51 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:145: Met Ser Met Phe Ile Ser Asn Leu Ala Phe Thr Ser 1 5 10 Ala Met Glu Val Ala Lys Ile Ala Ile Leu Leu Gly 25 Gly Ile Ile Gly Ala Leu Tyr Leu Phe Ala Leu Asp 40 Leu Lys Lys INFORMATION FOR SEQ ID NO:146: SEQUENCE CHARACTERISTICS: LENGTH: 449 amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...449 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:146: Met Gly Leu Lys Ile Lys Ile Leu Arg Leu Ser Met 1 5 10 Thr Glu Asn Ala Leu Ser Leu Thr Leu Lys Asn Phe 25 Ser Phe Gly Gly Ile Phe Leu Phe Leu Asn Ala Val Val Ala Asn Ser Phe Leu Lys Glu Ser Tyr Phe Ala 50 55 Pro Phe Gly Phe Gin Val Gly Asp Phe Phe Ile Gly 70 75 Asn Trp Ile Asp Asp Val Leu Met Ala Leu Phe Phe 90 Glu His Lys Asp Ser Leu Ile Ser Lys Arg Ala Ala Leu Lys Ala Trp Ser Met Lys Ser Met His Leu Ile Lys Glu Val Thr His Gly WO 98/24475 PCT/S97/22104 -227- Leu Glu Ile Lys Arg Glu Leu Leu Phe Gly Glu Leu Ser Ser Phe Lys 100 105 110 Lys Ala Ser Phe Pro Val Ile Ala Ala Ile Gly Gly Met Ile Ala Pro 115 120 125 Gly Leu Ile Tyr Phe Phe Leu Asn Ala Asn Thr Pro Ser Gin His Gly 130 135 140 Phe Gly Ile Pro Met Ala Thr Asp Ile Ala Phe Ala Leu Gly Val Ile 145 150 155 160 Met Leu Leu Gly Lys Arg Val Pro Thr Ala Leu Lys Val Phe Leu Ile 165 170 175 Thr Leu Ala Val Ala Asp Asp Leu Gly Ala Ile Val Val Ile Ala Leu 180 185 190 Phe Tyr Thr Thr Asn Leu Lys Phe Ala Trp Leu Leu Gly Ala Leu Gly 195 200 205 Val Val Leu Val Leu Ala Ile Leu Asn Arg Leu Asn Ile Arg Ser Leu 210 215 220 Ile Pro Tyr Leu Leu Leu Gly Val Leu Leu Trp Phe Cys Val His Gin 225 230 235 240 Ser Gly Ile His Ala Thr Ile Ala Ala Val Val Leu Ala Phe Met Ile 245 250 255 Pro Val Lys Ile Pro Lys Asp Ser Lys Asn Val Glu Leu Leu Glu Leu 260 265 270 Gly Lys Arg Tyr Ala Glu Thr Ser Ser Gly Val Leu Leu Thr Lys Glu 275 280 285 Gin Gin Glu Ile Leu His Ser Ile Glu Glu Lys Ala Ser Ala Leu Gin 290 295 300 Ser Pro Leu Glu Arg Leu Glu His Phe Leu Ala Pro Ile Ser Gly Tyr 305 310 315 320 Phe Ile Met Pro Leu Phe Ala Phe Ala Asn Ala Gly Val Ser Val Asp 325 330 335 Ser Ser Ile Asn Leu Glu Val Asp Lys Val Leu Leu Gly Val Ile Leu 340 345 350 Gly Leu Cys Leu Gly Lys Pro Leu Gly Ile Phe Leu Ile Thr Phe Ile 355 360 365 Ser Glu Lys Leu Lys Ile Thr Ala Arg Pro Lys Gly Ile Gly Trp Trp 370 375 380 His Ile Leu Gly Ala Gly Leu Leu Ala Gly Ile Gly Phe Thr Met Ser 385 390 395 400 Met Phe Ile Ser Asn Leu Ala Phe Thr Ser Glu His Lys Asp Ala Met 405 410 415 Glu Val Ala Lys Ile Ala Ile Leu Leu Gly Ser Leu Ile Ser Gly Ile 420 425 430 Ile Gly Ala Leu Tyr Leu Phe Ala Leu Asp Lys Arg Ala Ala Leu Lys 435 440 445 Lys INFORMATION FOR SEQ ID NO:147: SEQUENCE CHARACTERISTICS: LENGTH: 815 amino acids TYPE: amino acid TOPOLOGY: linear WO 98/24475 PCT/US97/22104 -228- (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...815 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:147: Met Asn Asp Lys Arg Phe Arg Lys Tyr Cys Ser Phe Ser Ile Phe Leu 1 5 10 Ser Leu Leu Gly Thr Phe Glu Leu Glu Ala Lys Glu Glu Glu Lys Glu 25 Glu Lys Lys Thr Glu Arg Asn Lys Asp Lys Glu Lys Asn Ala Gin His 40 Thr Leu Gly Lys Val Thr Thr Gin Ala Ala Lys Ile Phe Asn Tyr Asn 55 Asn Gin Thr Thr Ile Ser Ser Lys Glu Leu Glu Arg Arg Gin Ala Asn 70 75 Gin Ile Ser Asp Met Phe Arg Arg Asn Pro Asn Ile Asn Val Gly Gly 85 90 Gly Ala Val Ile Ala Gin Lys Ile Tyr Val Arg Gly Ile Glu Asp Arg 100 105 110 Leu Ala Arg Val Thr Val Asp Gly Val Ala Gin Met Gly Ala Ser Tyr 115 120 125 Gly His Gin Gly Asn Thr Ile Ile Asp Pro Gly Met Leu Lys Ser Val 130 135 140 Val Val Thr Lys Gly Ala Ala Gin Ala Ser Ala Gly Pro Met Ala Leu 145 150 155 160 Ile Gly Ala Ile Lys Met Glu Thr Arg Ser Ala Ser Asp Phe Ile Pro 165 170 175 Lys Gly Lys Asp Tyr Ala Ile Ser Gly Ala Ala Thr Phe Leu Thr Asn 180 185 190 Phe Gly Asp Arg Glu Thr Ile Met Gly Ala Tyr Arg Asn His His Phe 195 200 205 Asp Ala Leu Leu Tyr Tyr Thr His Gin Asn Ile Phe Tyr Tyr Arg Asp .210 215 220 Gly Asp Asn Ala Met Lys Asn Leu Phe Asp Pro Lys Ala Asp Asn Lys 225 230 235 240 Val Thr Ala Ser Pro Ser Glu Gin Asn Asn Val Met Ala Lys Ile Asn 245 250 255 Gly Tyr Leu Ser Glu Arg Asp Thr Leu Thr Leu Ser Tyr Asn Met lI 260 265 270 Arg Asp Asn Ala Asn Arg Pro Leu Arg Ala Asn Phe Thr Gly Thr Phe 275 280 285 Leu Pro Tyr Ser Cys Gly Asp Phe Asn Ala Phe Pro Asn Glu Lys Asn 290 295 300 Pro Ser Asp Cys Leu Phe Glu Asn Asp Ala Ser Leu Phe Lys Thr Tyr 305 310 315 320 Ser Val Asn Leu Val His Asn Val Ser Leu Asn Tyr Glu Arg Glu Gly WO 98/24475 PCT/US97/22104 -229- 325 330 335 Gly Ser Arg Phe Gly Asp Pro Lys Leu Lys Ile Asn Gly Tyr Thr Ser 340 345 350 Ile Arg Asn Val Gin Ile Asp Pro Leu Phe Arg Pro Ser Asp Ile Ala 355 360 365 Thr Thr Ile Pro Phe Thr Pro Asn Pro Gin Leu Ser Gin Gly Glu Glu 370 375 380 Asn Gin Cys Val Ala Gin Gly Gly Ile Tyr Asp Ala Leu Lys Gin Thr 385 390 395 400 Cys Ser Ile Thr Phe Lys Ser Leu Gly Gly Gly Ser Val Val Ala Asn 405 410 415 Lys Asn Leu Phe Ile Ile Asn Ser Gly Phe Asn Ala Asn Val Ile His 420 425 430 Thr Ile Asp His Lys Asn Asp Asn Leu Leu Glu Tyr Gly Leu Asn Tyr 435 440 445 Gin Asn Leu Thr Thr Phe Asp Lys Ala Ile Pro Asp Ser Glu Leu Val 450 455 460 Lys Pro Gly Asp Ala Pro Asp Ala Cys Leu Arg Val Thr Gly Pro Asp 465 470 475 480 Asp Pro Asn Met Asn Gly Arg Cys Gin Arg Asn Gly Ala Thr Ala Asn 485 490 495 Val Val Gly Val Tyr Ala Gin Ala Asn Tyr Thr Leu His Pro Met Val 500 505 510 Thr Leu Gly Ala Gly Thr Arg Tyr Asp Val Tyr Thr Leu Val Asp Lys 515 520 525 Asp Trp Gin Leu His Val Thr Gin Gly Phe Ser Pro Ser Ala Ala Leu 530 535 540 Asn Val Ser Pro Leu Glu Asn Leu Asn Phe Arg Leu Ser Tyr Ala Tyr 545 550 555 560 Val Thr Arg Gly Pro Met Pro Gly Gly Leu Val Trp Met Arg Gin Asp 565 570 575 Asn Leu Arg Tyr Asn Arg Asn Leu Lys Pro Glu Ile Gly Gin Asn Ala 580 585 590 Glu Phe Asn Thr Glu Tyr Ser Ser Gin Tyr Phe Asp Phe Arg Ala Ala 595 600 605 Gly Phe Val Gin Leu Ile Ser Asn Tyr Ile Asn Gin Phe Ser Ser Thr 610 615 620 Leu Phe Val Thr Asn Leu Pro Ala Gin Asp Ile Ile Tyr Val Pro Gly 625 630 635 640 Tyr Glu Val Ser Gly Thr Ala Lys Tyr Lys Gly Phe Ser Leu Gly Leu 645 650 655 Ser Val Ala Arg Ser Trp Pro Ser Leu Lys Gly Arg Leu Ile Ala Asp 660 665 670 Val Tyr Glu Leu Ala Ala Thr Thr Gly Asn Val Phe Ile Leu Thr Ala 675 680 685 Ser Tyr Thr Ile Pro Arg Thr Gly Leu Ee: Ile Thr Trp Leu Ser Arg 690 695 700 Phe Val Thr Asn Leu Ser Tyr Cys Ser Tyr Ser Pro Tyr Arg Asn Gly 705 710 715 720 Pro Thr Asp Ile Asp Arg Arg Pro Ser Asn Cys Pro Lys Thr Pro Gly 725 730 735 Ile Phe His Val His Lys Pro Gly Tyr Gly Val Ser Ser Phe Phe Ile 740 745 750 Thr Tyr Lys Pro Thr Tyr Lys Lys Leu Lys Gly Leu Ser Leu Asn Ala WO 98/24475 PCT/US97/22104 -230- 755 760 765 Val Phe Asn Asn Val Phe Asn Gin Gin Tyr Ile Asp Gin Ala Ser Pro 770 775 780 Val Met Ser Pro Asp Glu Pro Asn Gin Asp Lys Tyr Ala Arg Gly Met 785 790 795 800 Ala Glu Pro Gly Phe Asn Ala Arg Phe Glu Ile Ser Tyr Lys Phe 805 810 815 INFORMATION FOR SEQ ID NO:148: SEQUENCE CHARACTERISTICS: LENGTH: 814 amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...814 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:148: Met Thr Ser Val Leu Glu Lys Tyr Cys Ser Phe Ser 1 Leu Lys Leu Gin Ile Ala Ala His Val 145 Gly Gly Gly Leu Lys Gly Thr Ser Val Arg Gin 130 Thr Ala Lys Asp Gly Thr Lys Thr Asp Ile Val 115 Gly Lys Ile Asp Arg 195 Thr Glu Val Ile Met Ala 100 Thr Asnr Gly Lys Tyr 180 Glu 5 Phe Arg Thr Ser Phe 85 Gin Val Thr Ala Met 165 Ala Thr Glu Asn Thr Ser 70 Arg Lys Asp Ile Ala 150 Glu Ile Ile Leu Lys Gin 55 Lys Arg Ile Gly Ile 135 Gin Thr Ser Met Glu Asp 40 Ala Glu Asn Tyr Val 120 Asp Ala Arg Gly Gly 200 Ala 25 Lys Ala Leu Pro Val 105 Ala Pro Ser Ser Ala 185 Ala 10 Lys Glu Lys Glu Asn 90 Arg Gin Gly Ala Ala 170 Ala Tyr Glu Lys Ile Arg 75 Ile Gly Met Met Gly 155 Ser Thr Arg Glu Asn Phe Arg Asn Ile Gly Leu 140 Pro Asp Phe Asn Ile Glu Ala Asn Gin Val Glu Ala 125 Lys Met Phe Leu His 205 Phe Lys Gln Tyr Ala Gly Asp 110 Ser Ser Ala Ile Thr 190 His Leu Glu His Asn Asn Gly Arg Tyr Val Leu Pro 175 Asn Phe Ser Glu Thr Asn Gin Gly Leu Gly Val Ile 160 Lys Phe Asp WO 98/24475 WO 9824475PCTIUS97/22104 -231 Ala Asp 225 Thr Tyr Asp Pro Ser 305 Vzal Ser Arg Thr Gin 385 ser Asn Ile Asn Pro 465 Pro Vai Leu Trp, Val 545 Thr Leu Phe Phe Phe 625 Leu 210 Asn Ala Leu Asn Tyr 290 Asp Asn Arg Asn Ile 370 Cys Ile Leu Asp Leu 450 Gly Asn Gly Giy Gin 530 Ser Arg Arg Asn Val 610 Val Leu Ala Ser Ser Ala 275 Ser Cys Leu Phe Vai 355 Pro Val Thr Phe His 435 Thr Asp Met Val Ala 515 Leu Pro Giy Tyr Thr 595 Gin Thr Tyr Met Pro Giu 260 Asn Cys Leu Val Gly 340 Gin Phe Al a Phe Ile 420 Lys Thr Aila Asn Tyr 500 Gly His Leu Pro Asn 580 Giu Leu Asn Tyr Lys Ser 245 Arg Arg Gly Phe His 325 Asp Ile Thr Gin Lys 405 Ile Asn Phe Pro Gly 485 Ala Thr Val Giu Met 565 Arg Tyr Ile Leu Thr Asn 230 Giu Asp Pro Asp Glu 310 Asn Pro Asp Pro Giy 390 Ser Asn Asp Asp Asp 470 Arg Gin Arg Thr Asn 550 Pro Asn Ser Ser Pro 630 Gin Phe Asn Leu Arg 280 Asn Asp Ser Leu Leu 360 Pro Ile Gly Gly Leu 440 Ala Cys Gin Asn Asp 520 Gly Asn Gly Lys Gin 600 Tyr Gln Asn Asp Asn Thr 265 Ala Ala Ala Leu Lys 345 Phe Gln Tyr Gly Phe 425 Leu Ile Leu Arg Tyr 505 Val Phe Phe Leu Pro 585 Tyr Ile Asp Phe Lys 235 Met Ser Phe Pro Leu 315 Tyr Asn Pro Ser Ala 395 Ser Ala Tyr Asp Val 475 Gly Leu Thr Pro Leu 555 Trp Ile Asp Gin Ile 635 Tyr Asp Lys Asn Gly 285 Glu Lys Arg Tyr Asp 365 Gly Lys Val Val Leu 445 Glu Gly Thr Pro Val 525 Ala Tyr Arg Gln Arg 605 Ser Val Arg Asn Ile Met 270 Thr Lys Thr Giu Thr 350 Ile Glu Gin Ala Ile 430 Asn Leu Pro Ala Met 510 Asp Aia Ala Gin Asn 590 Ala Ser Pro Asp Lys Asn 255 Thr Phe Asn Tyr Gly 335 Ser Ala Giu Thr Asn 415 His Tyr Val1 Asp Asn 495 Val Lys Leu Tyr Asp 575 Ala Al a Thr Gly Gly Val 240 Gly Arg Leu Pro Ser 320 Giy Ile Thr Asn Cys 400 Lys Thr Gin Lys Asp 480 Val Thr Asp Asn Val 560 Asn Glu Gly Leu Tyr 640 WO 98/24475 PCT[S97/22104 -232- Glu Val Ser Gly Thr Ala Lys Tyr Lys Gly Phe Ser Leu Gly Leu Ser 645 650 655 Val Ala Arg Ser Trp Pro Ser Leu Lys Gly Arg Leu Ile Ala Asp Val 660 665 670 Tyr Glu Leu Ala Ala Thr Thr Gly Asn Val Phe Ile Leu Thr Ala Ser 675 680 685 Tyr Thr Ile Pro Arg Thr Gly Leu Ser Ile Thr Trp Leu Ser Arg Phe 690 695 700 Val Thr Asn Leu Ser Tyr Cys Ser Tyr Ser Pro Tyr Arg Asn Gly Pro 705 710 715 720 Thr Asp Ile Asp Arg Arg Pro Ser Asn Cys Pro Lys Thr Pro Gly Ile 725 730 735 Phe His Val His Lys Pro Gly Tyr Gly Val Ser Ser Phe Phe Ile Thr 740 745 750 Tyr Lys Pro Thr Tyr Lys Lys Leu Lys Gly Leu Ser Leu Asn Ala Val 755 760 765 Phe Asn Asn Val Phe Asn Gln Gin Tyr Ile Asp Gin Ala Ser Pro Val 770 775 780 Met Ser Pro Asp Glu Pro Asn Gin Asp Lys Tyr Ala Arg Gly Met Ala 785 790 795 800 Glu Pro Gly Phe Asn Ala Arg Phe Glu Ile Ser Tyr Lys Phe 805 810 INFORMATION FOR SEQ ID NO:149: SEQUENCE CHARACTERISTICS: LENGTH: 527 amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: miscfeature LOCATION 1...527 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:149: Met Lys Gin Asn Leu Lys Pro Phe Lys Met Ile Lys Glu Asn Leu Met 1 5 10 Thr Gin Ser Gin Lys Val Arg Phe Leu Ala Pro Leu Ser Ala Leu 25 Ser Leu Ser Phe Asn Pro Val Gly Ala Glu Glu Asp Gly Gly Phe Met 40 Thr Phe Gly Tyr Glu Leu Gly Gin Val Val Gin Gin Val Lys Asn Pro 55 Gly Lys Ile Lys Ala Glu Glu Leu Ala Gly Leu Leu Asn Ser Thr Thr 70 75 Thr Asn Asn Thr Asn Ile Asn Ile Ala Gly Thr Gly Gly Asn Val Ala WO 98/24475 PCT/US97/22104 -233- 90 Gly Thr Leu Gly Asn Leu Phe Met Asn Gin Leu Gly Asn Leu Ile Asp 100 105 110 Leu Tyr Pro Thr Leu Lys Thr Asn Asn Leu His Gin Cys Gly Ser Thr 115 120 125 Asn Ser Gly Asn Gly Ala Thr Ala Ala Ala Ala Thr Asn Asn Ser Pro 130 135 140 Cys Phe Gin Gly Asn Leu Ala Leu Tyr Asn Glu Met Val Asp Ser Ile 145 150 155 160 Lys Thr Leu Ser Gin Asn Ile Ser Lys Asn Ile Phe Gin Gly Asp Asn 165 170 175 Asn Thr Thr Ser Ala Asn Leu Ser Asn Gin Leu Ser Glu Leu Asn Thr 180 185 190 Ala Ser Val Tyr Leu Thr Tyr Met Asn Ser Phe Leu Asn Ala Asn Asn 195 200 205 Gin Ala Gly Gly Ile Phe Gin Asn Asn Thr Asn Gin Ala Tyr Glu Asn 210 215 220 Gly Val Thr Ala Gin Gin Ile Ala Tyr Val Leu Lys Gin Ala Ser Ile 225 230 235 240 Thr Met Gly Pro Ser Gly Asp Ser Gly Ala Ala Gly Ala Phe Leu Asp 245 250 255 Ala Ala Leu Ala Gin His Val Phe Asn Ser Ala Asn Ala Gly Asn Asp 260 265 270 Leu Ser Ala Lys Glu Phe Thr Ser Leu Val Gin Asn Ile Val Asn Asn 275 280 285 Ser Gin Asn Ala Leu Thr Leu Ala Asn Asn Ala Asn Ile Ser Asn Ser 290 295 300 Thr Gly Tyr Gin Val Ser Tyr Gly Gly Asn Ile Asp Gin Ala Arg Ser 305 310 315 320 Thr Gin Leu Leu Asn Asn Thr Thr Asn Thr Leu Ala Lys Val Thr Ala 325 330 335 Leu Asn Asn Glu Leu Lys Ala Asn Pro Trp Leu Gly Asn Phe Ala Ala 340 345 350 Gly Asn Ser Ser Gin Val Asn Ala Phe Asn Gly Phe Ile Thr Lys Ile 355 360 365 Gly Tyr Lys Gin Phe Phe Gly Glu Asn Lys Asn Val Gly Leu Arg Tyr 370 375 380 Tyr Gly Phe Phe Ser Tyr Asn Gly Ala Gly Val Gly Asn Gly Pro Thr 385 390 395 400 Tyr Asn Gin Val Asn Leu Leu Thr Tyr Gly Val Gly Thr Asp Val Leu 405 410 415 Tyr Asn Val Phe Ser Arg Ser Phe Gly Ser Arg Ser Leu Asn Ala Gly 420 425 430 Phe Phe Gly Gly Ile Gin Leu Ala Gly Asp Thr Tyr Ile Ser Thr Leu 435 440 445 Arg Asn Ser Pro Gin Leu Ala L1: Arg Pro Thr Ala Thr Lys Phe Gin 450 455 460 Phe Leu Phe Asp Val Gly Leu Arg Met Asn Phe Gly Ile Leu Lys Lys 465 470 475 480 Asp Leu Lys Ser His Asn Gin His Ser Ile Glu Ile Gly Val Gin Ile 485 490 495 Pro Thr Ile Tyr Asn Thr Tyr Tyr Lys Ala Gly Gly Ala Glu Val Lys 500 505 510 Tyr Phe Arg Pro Tyr Ser Val Tyr Trp Val Tyr Gly Tyr Ala Phe WO 98/24475 PCT/US97/22104 -234- 515 520 525 INFORMATION FOR SEQ ID NO:150: SEQUENCE CHARACTERISTICS: LENGTH: 459 amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...459 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:150: Val Val Leu Leu Thr Met Thr Lys Arg Leu Phe Lys Gly Leu Leu Ala 1 5 10 Ile Ser Leu Ala Val Ser Leu His Gly Gly Glu Val Lys Glu Lys Lys 25 Pro Val Lys Pro Val Lys Glu Asp Pro Gin Glu Leu Ala Ala Lys Arg 40 Val Glu Ala Phe Ser Arg Phe Ser Asn Val Val Thr Glu Ile Glu Lys 50 ss Lys Tyr Val Asp Lys Ile Ser Ile Ser Glu Ile Met Thr Lys Ala Ile 70 75 Glu Gly Leu Leu Ser Asn Leu Asp Ala His Ser Ala Tyr Leu Asn Glu 90 Lys Lys Phe Lys Glu Phe Gin Ala Gin Thr Glu Gly Glu Phe Gly Gly 100 105 110 Leu Gly Ile Thr Val Gly Met Arg Asp Gly Val Leu Thr Val Ile Ala 115 120 125 Pro Leu Glu Gly Thr Pro Ala Tyr Lys Ala Gly Val Lys Ser Gly Asp 130 135 140 Ser Ile Leu Lys Ile Asn Asn Glu Ser Thr Leu Ser Met Ser Ile Asp 145 150 155 160 Asp Ala Val Asn Leu Met Arg Gly Lys Pro Lys Thr Ser Ile Gin Ile 165 170 175 Thr Va 1 Val Arg Lys Asn Glu Pro Lys Pro Leu Val Phe Asn Ile Val 180 185 190 Arg Asp Ile Ile Lys Ile Pro Ser Val Tyr Val Lys Lys Ile Lys Asp 195 200 205 Thr Pro Tyr Leu Tyr Val Arg Val Asn Ser Phe Asp Lys Asn Val Thr 210 215 220 Lys Ser Val Leu Asp Gly Leu Lys Ala Asn Pro Asn Ile Lys Gly Val 225 230 235 240 Val Leu Asp Leu Arg Gly Asn Pro Gly Gly Leu Leu Asn Gin Ala Val 245 250 255 WO 98/24475 PCTfUlS97/22104 -235- Gly Gly Pro Ser 305 Ile Leu Tyr Ile Leu 385 Leu Ser Gin Glu Leu Lys Tyr 290 Ala Ile Pro Leu Val 370 Lys Asp Glu Leu Lys 450 Ser Asn 275 Thr Ser Ile Val Pro 355 Ile Glu Asp Glu Lys 435 Met Asn 260 Lys Asn Glu Gly Asn 340 Ser Tyr Ala Lys Glu 420 Thr Asp Leu Glu Leu Ile Glu 325 Lys Gly Pro Asp Thr 405 Lys Ala Glu Phe Glu Pro Val 310 Lys Asp Arg Gly Leu 390 Pro Glu Ile Lys Ile Asn Val 295 Ala Thr Glu Thr Lys 375 Lys Ile Val Asp Val 455 Lys Leu 280 Val Gly Phe Ala Ile 360 Val His Ser Thr Ser 440 Pro Glu 265 Glu Val Ala Gly Ile 345 Gin Pro His Lys Pro 425 Leu Lys Gly Val Tyr Lys Leu Val Leu Gin 315 Lys Gly 330 Lys Ile Ala Lys Glu Asn Leu Glu 395 Glu Ala 410 Lys Met Lys Thr Lys Lys Leu Ala Asn 300 Asp Ser Thr Gly Glu 380 Gin Asp Ile Trp Val Asn 285 Gly His Val Thr Ile 365 Asn Glu Lys Asn Ser 445 Ser 270 Gly Gly Lys Gin Ala 350 Thr Lys Leu Asp Asp 430 Ile Gin Arg Ser Arg Val 335 Arg Pro Phe Lys Lys 415 Asp Val Arg Ala Ala Ala 320 Leu Tyr Asp Ser Lys 400 Lys Ile Asp INFORMATION FOR SEQ ID NO:151: SEQUENCE CHARACTERISTICS: LENGTH: 104 amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...104 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:151: Leu Leu Leu His Pro Leu His Ala His Ala Gin Val Leu Gly Phe Thr 1 5 10 Asn His Asp His Ala Pro Trp Leu Tyr Asp Phe Ile Lys Ser Phe Cys 25 Asn Leu Ser Gly Gin Pro Phe Leu Asp Leu Gin Ala Phe Ala Ile Asn 40 Phe Asn Glu Phe Ser Asp Arg Ala Asn Ala Tyr Asn Leu Phe Leu Arg WO 98/24475 PCTIUS97/22104 -236- 55 Asp Ile Ser His Ala Asn Ile Pro Lys Lys Arg Glu Gin Met Val Leu 70 75 Ala Ser Gly Val Lys Phe Asn Val Leu Ser His Tyr His Phe Ile Ala 85 90 Asn Ala Leu Lys Ile Arg Ala Phe 100 INFORMATION FOR SEQ ID NO:152: SEQUENCE CHARACTERISTICS: LENGTH: 165 amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: miscfeature LOCATION 1...165 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:152: Met Ile Glu Leu Ile Leu His Asn Lys Ser Ile Gin Ile Asp Glu Thr 1 5 10 Leu Leu Asn Val Lys Glu His Leu Glu Lys Phe Tyr Ser Asn Lys Glu 25 Gin Glu Thr Ile Ala Lys Thr Leu Glu Ser Gin Thr Glu Leu Thr Cys 40 Ser Tyr Leu Leu Asp Lys Asp Phe Ser Leu Leu Glu Lys His Leu Glu 55 Asn Ser Leu Gly His Phe Thr Phe .Glu Ser Glu Phe Ala Leu Leu Lys 70 75 Asp Lys Glu Pro Leu Asn Leu Ala Gin Ile Lys Gin Ile Gly Val Leu 85 90 Lys Val Ile Thr Tyr Glu Met Thr Gin Ala Leu Lys Asn Gin Ile Ile 100 105 110 His Leu Thr Gin Ile Val Asn Glu Glu Asn Leu Glu Phe Asp Glu Glu 115 120 125 Leu Val Ile Tyr His Leu Asn Phe Lys Leu Asn Gin Asn Thr Tyr Lys 130 135 Val Leu Ala Lys Phe Cys Val Leu Lys Lys Lys Gly Thr Leu His Glu 145 150 155 160 Lys Phe Lys Ala Phe 165 INFORMATION FOR SEQ ID NO:153: SEQUENCE CHARACTERISTICS: WO 98/24475PCUS7Z10 PCTIUS97/22104 -237- LENGTH: 213 amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/kEY: misc feature LOCATION .213 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:i53: Met Asp Thr Glu Thr Gin Glu Lys Phe Leu Ala Tyr 1 Ala Lys Met Leu Gin Sen Asn Asp Lys 145 His Leu Val Lys Leu Asn Ile 50 Leu Giu Tyr Ser Lys 130 Vai Leu Val Leu Phe 210 Gin Giu Giu Asn Thr Leu Leu 115 Giu Ile Thr Ile Aia 195 Lys Lys Leu Leu Val Ile Leu 100 Gly Pro Thr Gin Tyr 180 Lys Ala 5 Asn Thr Ile Lys Ala Asp His Leu Tyr Ile 165 His Phe Phe Leu Arg Leu Giu 70 Lys Lys Phe Asn Giu 150 Vai Leu Cys Gin Giu His His Thr Asp Thr Leu 135 Met Asn Asn Val Al a Glu 40 Asn Leu Leu Phe Phe 120 Ala Thr Giu Phe Leu 200 Tyr 25 Phe Lys Giu Glu Sen 105 Glu Gin Gin Giu Lys 185 Lys Trp Ser Ser Lys Sen 90 Leu Ser Ile Ala Asn 170 Leu Lys Ile Asn Ile Phe 75 Gin Leu Giu Lys Leu 155 Leu Asn Lys Leu Thr Ile Ile Ser Glu Lys Ala 125 Ile Asn Phe Asn Thr 205 Phe Thr Arg Asp Asn Leu His 110 Leu Gly Gin Asp Thr 190 Leu Giu Giu Lys Giu Lys Thr Leu Leu Val Ile Giu 175 Tyr His Lys Thr Thr Thr Glu Cys Glu Lys Leu Ile 160 Giu Lys Glu INFORMATION FOR SEQ ID NO:154: SEQUENCE CHARACTERISTICS: LENGTH: 253 amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein WO 98/24475 WO 9824475PCTIUS97/22104 238 (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc-feature LOCATION .253 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:154: Met Ala Ile Ser Ile Lys Sen Pro Lys Giu Ile Lys 1 Ala Arg Ile Pro Pro Gly Ile Giu Lys 145 Val Giu Ser Val Val 225 Ala Gly Pro Lys 50 Asn Thr Val Gly Sen 130 Giu Pro Giu Gly Cys 210 Val Ile Giu Gly Ser Ser Asp Giu Ala 115 Leu Leu Leu Pro Pro 195 Gin Ser Val Leu Val Ser Val1 Tyr Val 100 Ile Met Ser Lys Giu 180 Lys Lys Val Gly 5 Thr Ser His Cys Val Asp Ser His Gin Gly 165 Ile Ile Gin Asp Asn 245 Ala Leu Al a Met 70 Leu Gly Pro Ala Ile 150 Phe Pro Lys Gly Gly 230 Lys Gin Leu Ang 55 Sen Gin Tyr Gin Ilie 135 Leu Cys Asn Glu Giu 215 Leu Ala Ala Giu 40 Pro Leu Glu Tyn Asp 120 Ser Glu Gly Tyr Gly 200 Pro Asn Val Leu 25 Leu Ala Asn Gly Gly 105 Giu Ser Gly His Leu 185 Met Lys Thr Ile 10 Ala Asp Phe Giu Asp 90 Asp Lys Ile Ala Gly 170 Glu Val Ile Ser Leu 250 Leu Lys Lys Val 75 Ile Sen Leu Arg Ile 155 Ile Lys Phe Leu His 235 Thr Leu Met Gly Val Ile Ala Leu Val 140 Thr Gly Gly Cys Al a 220 His Glu Al a Giu Al a Leu Ile Gly Leu Ala 125 Gly Giu Lys Val Leu 205 Asp Glu Arg Leu Arg Glu Tyr His Leu Thr 110 Cys Met Arg Lys Lys 190 Giu Lys His Arg Glu Asp Gly Gly Asp Leu Ser His Gly Pro 175 Al a Pro Trp Thr Lys Val Phe Phe Ile Leu Pro Lys Phe Phe 160 His Asn Met Ser Ile 240 INFORMATION FOR SEQ ID NO:155: SEQUENCE CHARACTERISTICS: LENGTH: 247 amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein WO 98/24475 PCT/US97/22104 -239- (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...247 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:155: Lys Pro Lys Arg Asn Gin Ser Pro Lys Lys Ser Arg 1 Gin Leu Arg Ser Gin Tyr Gin Ile Leu 145 Cys Asn Glu Glu Leu 225 Ala Ala Glu Pro Leu Glu Tyr Asp Ser 130 Glu Gly Tyr Gly Pro 210 Asn Val Leu Leu Ala Asn Gly Gly Glu 115 Ser Gly His Leu Met 195 Lys Thr Ile Ala 20 Asp Phe Glu Asp Asp 100 Lys Ile Ala Gly Glu 180 Val Ile Ser Leu 5 Leu Lys Lys Val Ile Ser Leu Arg Ile Ile 165 Lys Phe Leu His Thr 245 Leu Glu Met Ala Gly Leu 55 Val Ile 70 Ile Gly Ala Leu Leu Ala Val Gly 135 Thr Glu 150 Gly Lys Gly Val Cys Leu Ala Asp 215 His Glu 230 Glu Arg Arg Glu 40 Tyr His Leu Thr Cys 120 Met Arg Lys Lys Glu 200 Lys His Glu 25 Asp Gly Gly Asp Leu 105 Ser His Gly Pro Ala 185 Pro Trp Thr 10 Val Phe Phe Ile Leu 90 Pro Lys Phe Phe His 170 Asn Met Ser Ile Pro Lys Asn Thr Val Gly Ser Glu 140 Pro Glu Gly Cys Val 220 Ile Glu Gly Ser Ser Asp Glu Ala Leu 125 Leu Leu Pro Pro Gin 205 Ser Val Leu Val Ser Val Tyr Val Ile 110 Met Ser Lys Glu Lys 190 Lys Val Gly Thr Ser His Cys Val Asp Ser His Gin Gly Ile 175 Ile Gin Asp Asn Ala Leu Ala Met Leu Gly Pro Ala Ile Phe 160 Pro Lys Gly Gly Lys 240 INFORMATION FOR SEQ ID NO:156: SEQUENCE CHARACTERISTICS: LENGTH: 340 amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES WO 98/24475 PCT/US97/22104 -240- (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...340 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:156: Met Tyr Arg Lys Asp Leu Asp Asn Tyr Leu Lys Gin Arg Leu Pro Lys 1 5 10 Ala Val Phe Leu Tyr Gly Glu Phe Asp Phe Phe Ile His Tyr Tyr Ile 25 Gin Thr Ile Ser Ala Leu Phe Lys Gly Asn Asn Pro Asp Thr Glu Thr 40 Ser Leu Phe Tyr Ala Ser Asp Tyr Glu Lys Ser Gin Ile Ala Thr Leu 55 Leu Glu Gin Asp Ser Leu Phe Gly Gly Ser Ser Leu Val Ile Leu Lys 65 70 75 Leu Asp Phe Ala Leu His Lys Lys Phe Lys Glu Asn Asp Ile Asn Pro 90 Phe Leu Lys Ala Leu Glu Arg Pro Ser His Asn Arg Leu Ile Ile Gly 100 105 110 Leu Tyr Asn Ala Lys Ser Asp Thr Thr Lys Tyr Lys Tyr Thr Ser Glu 115 120 125 Ile Ile Val Lys Phe Phe Gin Lys Ser Pro Leu Lys Asp Glu Ala Ile 130 135 140 Cys Val Arg Phe Phe Thr Pro Lys Ala Trp Glu Ser Leu Lys Phe Leu 145 150 155 160 Gin Glu Arg Ala Asn Phe Leu His Leu Asp Ile Ser Gly His Leu Leu 165 170 175 Asn Ala Leu Phe Glu Ile Asn Asn Glu Asp Leu Ser Val Ser Phe Asn 180 185 190 Asp Leu Asp Lys Leu Ala Val Leu Asn Ala Pro Ile Thr Leu Glu Asp 195 200 205 Ile Gin Glu Leu Ser Ser Asn Ala Gly Asp Met Asp Leu Gin Lys Leu 210 215 220 Ile Leu Gly Leu Phe Leu Lys Lys Ser Val Leu Asp Ile Tyr Asp Tyr 225 230 235 240 Leu Leu Lys Glu Gly Lys Lys Asp Ala Asp Ile Leu Arg Gly Leu Glu 245 250 255 Arg Tyr Phe Tyr Gin Leu Phe Leu Phe Phe Ala His Ile Lys Thr Thr 260 265 270 Gly Leu Met Asp Ala Lys Glu Val Leu Gly "'yr Ala Pro Pro Lys Glu 275 280 285 Ile Val Glu Asn Tyr Ala Lys Asn Ala Leu Arg Leu Lys Glu Ala Gly 290 295 300 Tyr Lys Arg Val Phe Glu Ile Phe Arg Leu Trp His Leu Gin Ser Met 305 310 315 320 Gin Gly Gin Lys Glu Leu Gly Phe Leu Tyr Leu Thr Pro Ile Gin Lys 325 330 335 Ile Ile Asn Pro 340 WO 98/24475 WO 9824475PCT/US97/22104 -241- INFORMATION FOR SEQ ID NO:157: SEQUENCE CHARACTERISTICS: LENGTH: 200 amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 2 .200 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:157: Val Phe Met Thr Ser Ala Leu Leu Gly Leu Gin 1 Leu Gly Al a Ile Ser Pro Thr Gin Giu 145 Asn Pro Thr Ile Ala Ser s0 Asn Vai Al a Leu Thr 130 Sen Gly Thr Asn Val Tyr Phe Thr Leu Thr Asn Pro Pro Ile Thr Gin 195 Val 20 Ser Met Ile Asp Gly 100 Pro Lys Lys Lys His 180 Lys 5 Val Gly Al a Ala Glu Thr Leu Glu Gln Gly 165 Gln Lys Val Sen Lys Leu 70 Thr Leu Glu Leu Asn I50 Val Lys Asp Leu Asn Leu 55 Gly Lys Asn Gin Pro 135 Glu Glu Pro Glu Leu Asp 40 Thr Tyr Thn Pro Al a 120 Lys Lys Lys Lys Lys 200 10 Lys Leu Phe Tyr Lys Leu Thn Pro Glu Lys 170 His Ser Phe Leu Asn 75 Giu Asn Asn Ala Lys 155 Giu Ala Ile Ser Gly Gly Lys Leu Pro Pro Lys 140 Asn Asn Thr Val Sen Ala Leu Glu Ser Thr Leu 125 Thr Asp Al a Thr Leu Ile Lys Leu Tyr Pro Leu 110 Met Pro Ala Lys Asn 190 Ala Gly Gly Phe Gly Leu Asn Pro Phe Lys Thr 175 Ala Val Leu Pro Val Lys Val Pro Thr Val Giu 160 Pro His INFORMATION FOR SEQ ID NO:158: SEQUENCE CHARACTERISTICS: LENGTH: 159 amino acids TYPE: amino acid TOPOLOGY: linear WO 98/24475 PCT/US97/22104 -242- (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: miscfeature LOCATION 1...159 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:158: Met Arg Ser Pro Asn Leu Glu Lys Glu Glu Thr Glu Ile Ile Glu Thr 1 Leu Leu Leu Pro Gly Lys Pro Phe Arg 145 Leu Ala Leu Ile Val Leu Ser Leu 130 Ala Val Phe 35 Arg Tyr Tyr Val Arg 115 Cys Trp Lys Asp Ala Ala 70 Phe Ile Leu Leu Glu 150 Met Ser Phe Phe Phe Lys Leu Trp 135 Lys Arg Leu 40 Leu Val Val Ile Lys 120 Phe Ser Leu Leu His Val Cys lle 105 Arg Val Lys Pro Ala Leu Gly Cys Ile Gly Phe Leu 155 Tyr Leu Trp Ile Met Leu Lys 125 Asn Val Trp Leu Leu Ile Ser Ala 110 Ile Pro Leu Arg Ser Thr Leu Leu Asp Val Tyr Phe INFORMATION FOR SEQ ID NO:159: SEQUENCE CHARACTERISTICS: LENGTH: 234 amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: miscfeature LOCATION 1...234 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:159: WO 98/24475 PCTIS97/22104 -243- Leu Asn Thr Asp Phe Ser His Ile Thr Asp Ile Glu Gly Met Arg Phe 1 5 10 Val Asn Glu Glu Asp Ala Leu Asn Lys Leu Ile Asn Glu Ile His Thr 20 25 Arg His Ile Asp Leu Lys Asp Ser Ile Met Leu Ala Leu Ser Phe Asn 40 Ala Leu Tyr Leu Ala Asn Ala Leu Ala Gin Lys Phe Gly Ala Thr Tyr 55 Asp Ile Leu Phe Leu Glu Pro Ile Leu Ala Pro Leu Asn Ser Lys Cys 70 75 Glu Ile Ala Leu Val Ser Glu Ser Met Asp Ile Val Met Asn Glu Ser 90 Leu Ile Asn Ser Phe Asp Ile Ala Leu Asp Tyr Val Tyr Gly Glu Ala 100 105 110 Lys Arg Ala Tyr Glu Glu Asp Ile Leu Ser His Ile Tyr Gin Tyr Arg 115 120 125 Lys Gly Asn Ala Ile Lys Ser Leu Lys Asp Lys Asn Ile Phe Ile Val 130 135 140 Asp Arg Gly Ile Glu Thr Gly Phe Arg Ala Gly Leu Gly Val Gin Thr 145 150 155 160 Cys Leu Lys Lys Glu Cys Gin Asp Ile Tyr Ile Leu Thr Pro Ile Leu 165 170 175 Ala Gin Asn Val Ala Gin Gly Leu Glu Ser Leu Cys Asp Gly Val Ile 180 185 190 Ser Val Tyr Arg Pro Glu Cys Phe Val Ser Val Glu His His Tyr Lys 195 200 205 Glu Leu Lys Arg Leu Ser Asn Glu Glu Ile Glu Lys Tyr Leu Gly Ala 210 215 220 Asn Asn Ala Pro Asn Leu Lys Lys Glu His 225 230 INFORMATION FOR SEQ ID NO:160: SEQUENCE CHARACTERISTICS: LENGTH: 287 amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...287 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:160: Leu Lys Gin Ser Glu Met Ala Met Glu Phe Asn Asp Pro Arg Met Arg 1 5 10 WO 98/24475 PCTfUS97/22104 -244- Phe Phe Ile Gly Asp Val Arg Asp Glu Gly Ile Ala Ala Ser Ile Ala Ala Thr Lys Gly Val Gly 130 Asn Lys 145 Trp Ile Arg Met Met Ile Ile Gly 210 Asp Glu 225 Pro Thr His Glu Thr Asn Val Glu Asn Leu Lys Pro 115 Ser Ala Thr His Asp 195 Ile Ser Ile Lys Asn 275 Asp Tyr Val Ser Leu 100 Ser Arg Ser Leu Gly 180 Leu Arg His Ser Gly 260 Gin Ile Asn Ile Thr 85 Cys Gin Gly Glu Asp 165 Gly Ala Pro Leu Phe 245 Gin Trp Cys Pro Asn 70 Asp Ser Thr Ser Ile 150 Glu Glu Lys Gly Ala 230 Gin Lys Leu Ile Leu 55 Ala Lys Asp Gin Val 135 Pro Gly Ile Ala Glu 215 Leu Thr Val Glu His 40 Glu Cys Ala Lys Phe 120 Val Ile Val Phe Leu 200 Lys Glu Pro Ala Pro 280 Leu 25 Ala Cys Leu Ala Leu 105 Gly Pro Thr Ser Val 185 Ala Leu Phe Lys Pro 265 Asp Glu Ala Ile Lys Asn 90 Phe Val Phe Asp Phe 170 Pro Pro His Glu Asp 250 Asp Asp Arg Ala Lys Asn 75 Pro Val Val Phe Ile 155 Val Lys Asn Glu Asp 235 Tyr Phe Leu Leu Leu Thr Glu Ile Ser Arg Lys 140 Arg Leu Ile Ile Val 220 Phe Thr Glu Leu Asn Lys Asn Ile Asn Ala Tyr 125 Lys Met Lys Pro Pro 205 Met Phe Leu Tyr Lys 285 Tyr His Ile Ser Leu Asn 110 Gly Leu Thr Ser Ser 190 Thr Ile Ile Thr Ser 270 Leu Ala Val Met Gin Tyr Asn Asn Val Arg Leu 175 Met Lys Pro Ile Lys 255 Ser Leu Leu Pro Gly Val Gly Phe Val Gin Phe 160 Lys Lys Ile Lys Gin 240 Leu His INFORMATION FOR SEQ ID NO:161: SEQUENCE CHARACTERISTICS: LENGTH: 201 amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...201 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:161: WO 98/24475 PCT/US97/22104 -245- Met Arg Leu His Thr Ala Phe Phe Gly Ile Asn Ser Leu Leu Val Ala 1 5 10 Thr Leu Leu Ile Ser Gly Cys Ser Leu Phe Lys Lys Arg Asn Thr Asn 20 25 Ala Gin Leu Ile Pro Pro Ser Ala Asn Gly Leu Gin Ala Pro Ile Tyr 40 Pro Pro Thr Asn Phe Thr Pro Arg Lys Ser Ile Gin Pro Leu Pro Ser 55 Pro Arg Leu Glu Asn Asn Asp Gin Pro Ile Ile Ser Ser Asn Pro Thr 70 75 Asn Ala Ile Pro Asn Thr Pro Ile Leu Thr Pro Asn Asn Val Ile Glu 90 Leu Asn Ala Val Gly Met Gly Val Ala Pro Glu Ser Thr Ile Ser Pro 100 105 110 Ser Gin Ala Leu Ala Leu Ala Lys Arg Ala Ala Ile Val Asp Gly Tyr 115 120 125 Arg Gin Leu Gly Glu Lys Met Tyr Gly Ile Arg Val Asn Ala Gin Asp 130 135 140 Thr Val Lys Asp Met Val Leu Gin Asn Ser Val Ile Lys Thr Arg Val 145 150 155 160 Asn Ala Leu Ile Arg Asn Ala Glu Ile Thr Glu Thr Ile Tyr Lys Asp 165 170 175 Gly Leu Cys Gin Val Ser Met Glu Leu Lys Leu Asp Gly Arg Ile Trp 180 185 190 Tyr Arg Ile Leu Ser Gly Ser Arg Gly 195 200 INFORMATION FOR SEQ ID NO:162: SEQUENCE CHARACTERISTICS: LENGTH: 355 amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...355 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:162: Met Ser Tyr Thr Ile Asn Lys Arg Phe Ser Val Gly Val Gly Leu Arg 1 5 10 Gly Leu Tyr Ala Thr Gly Ser Phe Asn Asn Thr Val Tyr Val Pro Leu 25 Glu Gly Ala Ser Val Leu Ser Ala Glu Gin Ile Leu Asn Leu Pro Asn 40 WO 98/24475 PCT/US97/22104 -246- Asn Val Phe Ala Asp Gin Val Pro Ser Asn Met Met Thr Leu Leu Gly 55 Asn Ile Gly Tyr Gin Pro Ala Leu Asn Cys Gin Lys Ala Gly Gly Asp 70 75 Met Ser Asp Gin Ser Cys Gin Glu Phe Tyr Asn Gly Leu Lys Lys Ile 90 Met Gly Tyr Ser Gly Leu Ile Lys Ala Ser Ala Asn Leu Tyr Gly Thr 100 105 110 Thr Gin Val Val Gin Lys Ser Asn Gly Gin Gly Val Ser Gly Gly Tyr 115 120 125 Arg Val Gly Ser Ser Leu Arg Val Phe Asp His Gly Met Phe Ser Val 130 135 140 Val Tyr Asn Ser Ser Val Thr Phe Asn Met Lys Gly Gly Leu Val Ala 145 150 155 160 Ile Thr Glu Leu Gly Pro Ser Leu Gly Ser Val Leu Thr Lys Gly Ser 165 170 175 Leu Asn Ile Asn Val Ser Leu Pro Gin Thr Leu Ser Leu Ala Tyr Ala 180 185 190 His Gin Phe Phe Lys Asp Arg Leu Arg Val Glu Gly Val Phe Glu Arg 195 200 205 Thr Phe Trp Ser Gin Gly Asn Lys Phe Leu Val Thr Pro Asp Phe Ala 210 215 220 Asn Ala Thr Tyr Lys Gly Leu Ser Gly Thr Val Ala Ser Leu Asp Ser 225 230 235 240 Glu Thr Leu Lys Lys Met Val Gly Leu Ala Asn Phe Lys Ser Val Met 245 250 255 Asn Met Gly Ala Gly Trp Arg Asp Thr Asn Thr Phe Arg Leu Gly Val 260 265 270 Thr Tyr Met Gly Lys Ser Leu Arg Leu Met Gly Ala Ile Asp Tyr Asp 275 280 285 Gin Ala Pro Ser Pro Gin Asp Ala Ile Gly Ile Pro Asp Ser Asn Gly 290 295 300 Tyr Thr Val Ala Phe Gly Thr Lys Tyr Asn Phe Arg Gly Phe Asp Leu 305 310 315 320 Gly Val Ala Gly Ser Phe Thr Phe Lys Ser Asn Arg Ser Ser Leu Tyr 325 330 335 Gin Ser Pro Thr Ile Gly Gin Leu Arg Ile Phe Ser Ala Ser Leu Gly 340 345 350 Tyr Arg Trp 355 INFORMATION FOR SEQ ID NO:163: SEQUENCE CHARACTERISTICS: LENGTH: 587 amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori WO 98/24475 PCT[S97/22104 -247- (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...587 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:163: Met Lys Asn Phe Ser Pro Leu Tyr Cys Leu Lys Lys Leu Lys Lys Arg 1 5 10 His Leu Ile Ala Leu Ser Leu Pro Leu Leu Ser Tyr Ala Asn Gly Phe 25 Lys Ile Gin Glu Gin Ser Leu Asn Gly Thr Ala Leu Gly Ser Ala Tyr 40 Val Ala Gly Ala Arg Gly Ala Asp Ala Ser Phe Tyr Asn Pro Ala Asn 50 55 Met Gly Phe Thr Asn Asp Trp Gly Glu Asn Arg Ser Glu Phe Glu Met 70 75 Thr Thr Thr Val Ile Asn Ile Pro Ala Phe Ser Phe Lys Val Pro Thr 90 Thr Asn Gin Gly Leu Tyr Ser Val Thr Ser Leu Glu Ile Asp Lys Ser 100 105 110 Gin Gin Asn Ile Leu Gly Ile Ile Asn Thr Ile Gly Leu Gly Asn Ile 115 120 125 Leu Lys Ala Leu Gly Asn Thr Ala Ala Thr Asn Gly Leu Ser Gin Ala 130 135 140 Ile Asn Arg Val Gin Gly Leu Met Asn Leu Thr Asn Gin Lys Val Val 145 150 155 160 Thr Leu Ala Ser Lys Pro Asp Thr Gin Ile Val Asn Gly Trp Thr Gly 165 170 175 Thr Thr Asn Phe Val Leu Pro Lys Phe Phe Tyr Lys Thr Arg Thr His 180 185 190 Asn Gly Phe Thr Phe Gly Gly Ser Phe Thr Ala Pro Ser Gly Leu Gly 195 200 205 Met Lys Trp Asn Gly Lys Gly Gly Glu Phe Leu His Asp Val Phe Ile 210 215 220 Met Met Val Glu Leu Ala Pro Ser Met Ser Tyr Thr Ile Asn Lys Arg 225 230 235 240 Phe Ser Val Gly Val Gly Leu Arg Gly Leu Tyr Ala Thr Gly Ser Phe 245 250 255 Asn Asn Thr Val Tyr Val Pro Leu Glu Gly Ala Ser Val Leu Ser Ala 260 265 270 Glu Gin Ile Leu Asn Leu Pro Asn Asn Val Phe Ala Asp Gin Val Pro 275 280 285 Ser Asn Met Met Thr Leu Leu Gly Asn Ile Gly Tyr Gin Pro Ala Leu 290 295 300 Asn Cys Gin Lys Ala Gly Gly Asp Met Ser Asp Gin Ser Cys Gin Glu 305 310 315 320 Phe Tyr Asn Gly Leu Lys Lys Ile Met Gly Tyr Ser Gly Leu Ile Lys 325 330 335 Ala Ser Ala Asn Leu Tyr Gly Thr Thr Gin Val Val Gin Lys Ser Asn 340 345 350 Gly Gin Gly Val Ser Gly Gly Tyr Arg Val Gly Ser Ser Leu Arg Val 355 360 365 Phe Asp His Gly Met Phe Ser Val Val Tyr Asn Ser Ser Val Thr Phe

L

WO 98/24475 PTU9/20 PCTfUS97/22104 248 Asn 385 Gly Gin Arg Phe Gly 465 Leu Thr Leu Ile Tyr 545 Lys Arg 370 Met Ser Thr Val Leu 450 Thr Ala Asn Met Gly 530 Asn Ser Ile Lys Val Leu Giu 435 Vai Vai Asn Thr Giy 515 Ile Phe Asn Phe Giy Leu Ser 420 Giy Thr Ala Phe Phe 500 Ala Pro Arg Arg Ser 580 Gly Thr 405 Leu Val Pro Ser Lys 485 Arg Ile Asp Gly Ser 565 Ala Leu 390 Lys Aia Phe Asp Leu 470 Ser Leu Asp Ser Phe 550 Ser Ser 375 Vai Gly Tyr Glu.

Phe 455 Asp Vai Gly Tyr Asn 535 Asp Leu Leu Aia Ser Ala Arg 440 Ala Ser Met Vai Asp 520 Gly Leu Tyr Giy Ile Leu His 425 Thr Asn Glu Asn Thr 505 Gin Tyr Gly Gin Tyr 585 380 Leu Asn Phe Ser Tyr 460 Lys Ala Gly Ser Al a 540 Gly Thr Gly Val Lys Gin 445 Lys Lys Gly Lys Pro 525 Phe Ser Ile Pro Ser Asp 430 Gly Gly Met Trp Ser 510 Gin Gly Phe Gly Ser Leu 415 Arg Asn Leu Val Arg 495 Leu Asp Thr Thr Gin 575 Leu 400 Pro Leu Lys Ser Giy 480 Asp Arg Al a Lys Phe 560 Leu (2) Leu 1 Leu Lys INFORMATION FOR SEQ ID NO:164: SEQUENCE CHARACTERISTICS: LENGTH: 205 amino acids TYPE: amino acid TOPOLOGY: iinear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Heiicobacter pylori (ix) FEATURE: NAME/KEY: misc -feature LOCATION I .205 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:164: Ile Phe Arg Phe Phe Leu Ile Leu Ser Leu Leu Lys Giy Vai Leu 5 10 Ala Lys Lys Asp Trp Asn Phe Phe Lys Pro Leu Glu Pro Thr Lys 25 Tyr Phe Gly Ser Phe Lys Ile Gly Tyr Leu Tyr Gin His Ala Giu 40 WO 98/24475 PCTfUS97/22104 -249- Thr Thr Lys Arg Phe Pro Ile Arg Pro Lys Asn Arg Pro Pro Ile Leu 55 Met Asp Lys Ile Tyr His Asp Ala Ser Leu Gly Phe Asp Ala Gly Tyr 70 75 Val Leu Lys Lys Lys Ala Leu Leu Gly Gly Tyr Leu Asp Ala Gly Met 90 Gly Asp Ser Tyr Phe Met Ser Ala Gly Leu Val Ala Gly Val Arg Leu 100 105 110 Phe Lys Gly Trp Val Ile Pro Lys Ile Ala Leu Gly Tyr Gin Leu Gin 115 120 125 Ile Leu Gly Ala Lys Ile Asp Lys Tyr Gin Phe Asn Ile Gin Ser Ala 130 135 140 Val Gly Ser Val Gly Leu Phe Phe Asn Ala Ala Lys Asn Phe Gly Leu 145 150 155 160 Ser Ile Glu Ala Arg Gly Gly Ile Pro Phe Tyr Phe Ile Gin Ser Arg 165 170 175 Phe Ser Lys Ala Phe Gly Thr Pro Arg Leu Asn Ile Tyr Ser Val Gly 180 185 190 Ile Thr Phe Thr Phe Tyr Asp Phe Thr Arg Phe Leu Gly 195 200 205 INFORMATION FOR SEQ ID NO:165: SEQUENCE CHARACTERISTICS: LENGTH: 253 amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: miscfeature LOCATION 1...253 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:165: Leu Trp His Ala Ala Phe Ser Val Gly Glu Trp Gly Trp Asn Gly Asp 1 5 10 Glu Ile Pro Tyr Arg Asp Cys Asp Glu Trp Gly Leu Asp Asp Phe Tyr 20 25 Gly Val Lys Pro Thr As. :ys Ala Gly Val Leu Ser Phe Ala Arg Ser 40 His Arg Arg Gin Asn Gin Ala Val Leu Ser Lys Pro Lys Ser Phe Arg 55 Met Lys Lys Ile Ala Phe Ile Leu Ala Leu Trp Val Gly Leu Leu Gly 70 75 Ala Phe Glu Pro Lys Lys Ser His Ile Tyr Phe Gly Ala Met Val Gly 90 Leu Ala Pro Val Lys Ile Thr Pro Lys Pro Ala Ser Asp Ser Ser Tyr WO 98/24475 PCT/EJS97/22104 -250- Thr Lys Pro 145 Asp Tyr Met Leu Ile 225 Glu Ala Ala 130 Thr Val Gly Lys Gly 210 Pro Ser 100 Leu Ala Leu Ser Leu 180 Ser Thr Ser Phe Trp Leu His Asp 165 Gly Ser Ile Lys Ile 245 Gly Arg Thr 150 Phe Ile Phe Asp Thr 230 His Ala Gly 135 Ile Tyr Gly Met Arg 215 Arg Ala 105 Gly Phe Thr Tyr Phe 185 Tyr His Ser Tyr Tyr Tyr Leu 155 Lys Gin Gly Val Lys 235 Tyr Gin Leu 140 Leu Tyr Ser Leu Glu 220 Asn Met 110 Ala Ala Leu Phe His 190 Asn Gly Tyr Phe Lys Met 160 Val Gly Gly Lys Leu 240 INFORMATION FOR SEQ ID NO:166: SEQUENCE CHARACTERISTICS: LENGTH: 412 amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...412 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:166: Met Glu Ser Val Lys Thr Val Lys Thr Asn Lys Val 1 5 10 Glu Thr Ala Asn Thr Glu Ala Ser Lys Glu Thr His ser Ala Ile Thr Asn Thr Leu Arg Ser Ile Gly Gly 40 Ile Ala Lys Lys Val Arg Glu Leu Val Lys Lys His 55 Ser Val Ala Leu Val Val Leu Thr His Ile Ala Cys 65 70 75 Glu Leu Asp Asp Lys Val Gin Asp Lys Ser Lys Gin 90 Asn Gin Ile Asn Trp Trp Lys Tyr Ser Gly Leu Thr 100 105 Gly Phe Ile Pro Lys Ala Ile Asn Gin Thr Lys Ala Lys Ala Thr Ala Lys Ser Lys Glu Ser WO 98/24475 PCT/US97/22104 -251 Leu Leu Gin 145 Glu Glu Glu Gin Lys 225 Gin Ile Thr Pro Gin 305 Gin Pro Ile Ala Ala 385 Thr Leu Glu 130 Glu Ile Leu Gin Lys 210 Asp Leu Ala Asn Arg 290 Lys Val Arg Arg His 370 Asp Glu Leu 115 Gin Arg Glu Ala Glu 195 Gin Phe Phe Ile Gin 275 Ser Glu Asp Asp Ser 355 Leu Ile Lys Ala Lys Lys Glu 165 Ser Gin Thr Lys Lys 245 Ile Pro Arg Glu Tyr 325 Lys Ala Thr Lys Gly 405 Cys Lys Thr 150 Gin Gin Lys Ile Glu 230 Lys Glu Ile Gly Ser 310 Lys Val Gin Ser Glu 390 Tyr Ser Glu 135 Glu Glu Ile Ala Asn 215 Thr Ala Ala Gin Ser 295 Leu Pro Thr Ala Gin 375 Ile Gly Thr 120 Ala Gin Arg Lys Asn 200 Thr Glu Arg Glu Pro 280 Lys Pro Ser Glu Lys 360 Ser Glu Tyr Asp Lys Arg Lys 170 Glu Ser Arg Asn Lys 250 Lys His Gin Ser Ile 330 Trp Leu Leu Val Lys 410 Ile Ser Gin 155 Thr Gin Glu Asp Cys 235 Thr Thr Leu Glu Gin 315 Ala Gin Glu Phe Ala 395 Arg Asp Gly 140 Lys Asn Glu Ile Leu 220 Gin Gly Pro Pro Leu 300 Lys Tyr Lys Met Val 380 Asn Met Lys 125 Ile Thr Lys Arg Glu 205 Ile Glu Ile Lys Asn 285 Ile Ala Leu Glu Arg 365 Gin Thr Gin Lys Asn Ser Gin 190 Leu Lys Lys Thr Pro 270 Ser Ala Ile Glu Asn 350 Asn Lys Glu Ile Leu Lys Gly 175 Lys Glu Glu His Thr 255 Ala Lys Tyr Ala Leu 335 Leu Pro Ile Lys Glu Glu Ser 160 Ile Thr Gin Gin Gly 240 Gly Lys Gin Leu Lys 320 Asp Lys Gin Phe Lys 400 INFORMATION FOR SEQ ID NO:167: SEQUENCE CHARACTERISTICS: LENGTH: 149 amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: WO 98/24475 PCT/US97/22104 -252- NAME/KEY: miscfeature LOCATION 1...149 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:167: Leu Asn Trp Glu His Leu Met Lys Lys Leu Ala Phe Ser Leu Leu Phe 1 5 10 Thr Gly Thr Phe Leu Gly Leu Phe Leu Asn Ala Ser Asp Phe Lys Ser 25 Met Asp Asn Lys Gin Leu Leu Glu Gin Ala Gly Lys Val Ala Pro Ser 40 Glu Val Pro Glu Phe Arg Thr Glu Val Asn Lys Arg Leu Glu Ala Met 55 Lys Glu Glu Glu Arg Gin Lys Tyr Lys Ala Asp Phe Lys Lys Ala Met 65 70 75 Asp Lys Asn Leu Ala Ser Leu Ser Gin Glu Asp Arg Asn Lys Arg Lys 90 Lys Glu Ile Leu Glu Val Ile Ala Asn Lys Lys Lys Thr Met Thr Met 100 105 110 Lys Glu Tyr Arg Glu Glu Gly Leu Asp Leu His Asp Cys Ala Cys Glu 115 120 125 Gly Pro Phe His Asp His Glu Lys Lys Gly Gin Lys Gly Lys Lys Pro 130 135 140 Ser His His Lys His 145 INFORMATION FOR SEQ ID NO:168: SEQUENCE CHARACTERISTICS: LENGTH: 204 amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc_feature LOCATION 1...204 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:368: Met Gin Ala Val Ile Leu Ala Asn Gly Glu Phe Pro Lys Ser Lys Lys 1 5 10 Cys Leu Asp Ile Leu Gin Asn Ala Pro Phe Leu Ile Ala Cys Asp Gly 20 25 Ala Val Ile Ser Leu His Ala Leu Gin Phe Lys Pro Ser Val Val Ile 40 Gly Asp Leu Asp Ser Ile Asp Ser His Leu Lys Ala Leu Tyr Asn Pro 55 WO 98/24475 PCT/US97/22104 -253- Ile Arg Val Ser Glu Gin Asp Ser Asn Asp Leu Ser Lys Ala Phe Phe 70 75 Tyr Ala Leu Asn Arg Gly Cys Asp Asp Phe Ile Phe Leu Gly Leu Asn 90 Gly Lys Arg Glu Asp His Ala Leu Ala Asn Thr Phe Leu Leu Leu Glu 100 105 110 Tyr Phe Lys Phe Cys Lys Lys Ile Gin Ser Val Ser Asp Tyr Gly Leu 115 120 125 Phe Arg Val Leu Glu Thr Pro Phe Thr Leu Pro Ser Phe Lys Gly Glu 130 135 140 Gin Ile Ser Leu Phe Ser Leu Asp Leu Lys Ala Arg Phe Thr Ser Lys 145 150 155 160 Asn Leu Lys Tyr Pro Leu Lys Asp Leu Arg Leu Lys Thr Leu Phe Ser 165 170 175 Gly Ser Leu Asn Glu Ala Thr Asn His Cys Phe Ser Leu Ser Ser Glu 180 185 190 Pro Lys Ser Val Val Leu Val Tyr Gin Lys Phe Ser 195 200 INFORMATION FOR SEQ ID NO:169: SEQUENCE CHARACTERISTICS: LENGTH: 280 amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...280 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:169: Val Phe Asp Ser Leu Gly Gly Phe Leu Gly Tyr Lys Thr Phe Lys Pro 1 5 10 Ile Val Asp Lys Val Lys Asn Ile Asn Ala Trp Ile Lys Asn Tyr Asp 25 Asn Lys Lys Ala Gin Glu Ile Met Gly Phe Ile Glu Asn Pro Thr Pro 35 40 Asp Phe Gin As,. :.sn Lys Phe Leu Cys Val Leu Asn Arg Gin Gly Thr 55 Arg His Asn Asn Tyr Leu Gly Leu Thr Ser Thr Asn Leu Leu Ile Gly 70 75 Ala Ile Tyr Phe Ser Ile Arg His Cys Ile Lys Ala Thr Trp Gin Asn 90 Asp Arg Asp Gin Phe Tyr Ala Pro Tyr Asp Asp Ala Phe Gin Asp Asp 100 105 110 Ser Glu Phe Lys Asn Asn Cys Leu Ala Phe Met Leu Phe His Thr Gin WO 98/24475 PCT/US97/22104 -254- 115 120 125 Asn Arg Ile Thr Ala Thr Gin Gly Thr Asn His Phe Ile Pro Phe Ser 130 135 140 Glu Asp Glu Val Asp Ser Lys Glu Arg Tyr Leu Ser His Ala Leu Leu 145 150 155 160 Asp Phe Leu Lys Gly Glu Ile Lys Glu Pro Lys Lys Ser Asp Ser Leu 165 170 175 Phe Leu Asn Ala Lys Lys Glu Asn Lys Pro Leu Lys Phe Ser Ser Ser 180 185 190 Ala Ser Lys Val Phe Asp Ala Gly Arg Glu Ile Tyr Arg Tyr Tyr His 195 200 205 Thr Gin Asp Phe Ile His Thr Pro Tyr Asn Ala Asn Ala Ser Leu Tyr 210 215 220 Asp Ile Lys Glu Phe Phe Gin Gly Arg Asn Lys Gin Gly Arg Leu Asn 225 230 235 240 Ser Pro Thr Lys Ala Lys Asp Glu Tyr Tyr Lys Gin Leu Tyr Ala Asn 245 250 255 Leu Gin Tyr Ala Leu Lys Asp Leu Ala Lys Glu Ile Gin Pro Lys Val 260 265 270 Tyr Glu Tyr Gly Phe Leu Arg Glu 275 280 INFORMATION FOR SEQ ID NO:170: SEQUENCE CHARACTERISTICS: LENGTH: 309 amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: miscfeature LOCATION 1...309 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:170: Cys Asp Arg Ala Ile Pro His Trp Leu Phe Ser Leu Gly Tyr Arg Tyr 1 5 10 Pro Pro Pro Leu Lys Pro Thr Asn Ala Phe Asn Leu Glu Val Phe Asp 25 Ser Leu Gly Gly Phe Leu Gly Tyr Lys Thr Phe Lys Pro Ile Val Asp 40 Lys Val Lys Asn Ile Asn Ala Trp Ile Lys Asn Tyr Asp Asn Lys Lys 50 55 Ala Gin Glu Ile Met Gly Phe Ile Glu Asn Pro Thr Pro Asp Phe Gin 70 75 Asn Asn Lys Phe Leu Cys Val Leu Asn Arg Gin Gly Thr Arg His Asn 90 WO 98/24475 PCT/US97/22104 -255- Asn Tyr Leu Gly Leu Thr Ser Thr Asn Leu Leu Ile Gly Ala Ile Tyr 100 105 110 Phe Ser Ile Arg His Cys Ile Lys Ala Thr Trp Gin Asn Asp Arg Asp 115 120 125 Gin Phe Tyr Ala Pro Tyr Asp Asp Ala Phe Gin Asp Asp Ser Glu Phe 130 135 140 Lys Asn Asn Cys Leu Ala Phe Met Leu Phe His Thr Gin Asn Arg Ile 145 150 155 160 Thr Ala Thr Gin Gly Thr Asn His Phe Ile Pro Phe Ser Glu Asp Glu 165 170 175 Val Asp Ser Lys Glu Arg Tyr Leu Ser His Ala Leu Leu Asp Phe Leu 180 185 190 Lys Gly Glu Ile Lys Glu Pro Lys Lys Ser Asp Ser Leu Phe Leu Asn 195 200 205 Ala Lys Lys Glu Asn Lys Pro Leu Lys Phe Ser Ser Ser Ala Ser Lys 210 215 220 Val Phe Asp Ala Gly Arg Glu Ile Tyr Arg Tyr Tyr His Thr Gin Asp 225 230 235 240 Phe Ile His Thr Pro Tyr Asn Ala Asn Ala Ser Leu Tyr Asp Ile Lys 245 250 255 Glu Phe Phe Gin Gly Arg Asn Lys Gin Gly Arg Leu Asn Ser Pro Thr 260 265 270 Lys Ala Lys Asp Glu Tyr Tyr Lys Gin Leu Tyr Ala Asn Leu Gin Tyr 275 280 285 Ala Leu Lys Asp Leu Ala Lys Glu Ile Gin Pro Lys Val Tyr Glu Tyr 290 295 300 Gly Phe Leu Arg Glu 305 INFORMATION FOR SEQ ID NO:171: SEQUENCE CHARACTERISTICS: LENGTH: 187 amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: miscfeature LOCATION 1...187 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:171: Leu Glu Thr Tyr Ile Ile Asp Ala Asp Asn Ile Asp Gly Asp Leu Phe 1 5 10 Phe Tyr Asn Leu Thr Arg Asn Ser Asn Asp Phe Ser Met Leu Pro Val 25 Phe Glu Leu Asp Arg Ile Ala Gin Lys Ile Arg Asn Ile Leu Lys Lys WO 98/24475 PTU9/20 PCTIUS97/22104 -256- Ile Giu His Gly Ser Arg Lys Asp Ile Leu Lys His Asn Ile Lys Giu 55 Al a 65 Leu Tyr Trp Ile Gin 145 Asn Ile Phe Ser Leu Asp Ser 130 Asp Ser Tyr Phe His Giu Tyr 115 Lys Met Vai Giu Pro His Lys Asp Giu Giu Asn 165 Leu Phe 70 Aia Thr Asp Asp Lys i50 Gin Lys Lys Asp Lys Val Ala 135 Cys Gly Ile Pro Lys Arg Leu 120 Phe Pro Leu Ala Gin Asn Lys 105 Asn Thr Tyr Ser Ser 185 Leu Lys 90 Val Lys Leu Phe Arg 170 Phe Lys 75 Ala Phe Leu Ile Val1 155 Ile Tyr Thr Leu Ile Al a Leu 140 Phe Thr Val Gly Asp Lys 125 Arg Leu Tyr Gin Val Ser 1.10 His Lys Gin Ser Val Lys Leu Asp Ser Ser Ala 175 Phe Asp Phe Asp Leu Lys 160 Trp INFORMATION FOR SEQ ID NO:172: SEQUENCE CHARACTERISTICS: LENGTH: 198 amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pyloni (ix) FEATURE: NAME/KEY: misc feature LOCATION .198 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:172: Leu Glu Thr Tyr Ile Ile Asp Ala Asp Asn Ile Asp 1 5 10 Phe Tyr Asn Leu Thr Arg Asn Sen Asn Asp Phe Sen 25 Phe Giu Leu Asp Arg Ile Ala Gin Ly!; Ile Arg Asn His Gly Ser Arg Lys Asp Ile Ile Leu Lys His Asn 55 Ala Phe Phe Ser Pro Phe Lys Pro Gin Leu Lys Thr 65 70 75 Leu Ser His Ser His Ala Asp Lys Asn Lys Ala Leu 90 Tyr Leu Giu Sen Lys Thr Lys Ang Lys Val Phe Ile 100 105 Asp Leu Leu le Gin Val Sen 110 Leu Pro Lys Lys Val Lys Leu Phe Val Lys Giu Phe Asp Phe WO 98/24475 PTU9/20 PCTIUS97/22104 -257- Trp Asp Tyr Lys Asp Asp Val Leu Asn Lys Leu Ala Lys His Asp Asp 115 120 125 Ile Ser Lys Ile Glu Asp Ala Phe Thr Leu Ile Leu Arg Lys Ser Leu 130 135 140 Gin Asp Met Ile Giu Lys Cys Pro Tyr Phe Val Phe Leu Gin. Ser Lys 145 150 155 160 Asn Ser Vai Ser Asn Gin Gly Leu Ser Arg Ile Thr Tyr Ser Ala Trp 165 170 175 Ile Tyr Glu Giu Leu Lys Ile Ala Ser Phe Leu Leu Ala Leu Leu Thr 180 185 190 Arg Val Ala Gin Phe Gin 195 INFORMATION FOR SEQ ID NO:173: SEQUENCE CHARACTERISTICS: LENGTH: 189 amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Heiicobacter pyloni (ix) FEATURE: NAME/KEY: misc feature LOCATION 1 189 (xi) SEQUENCE DESCRIPTION: SEQ, ID NO:173: Met Met Thr Lys Asn Ala Tyr Ala Phe Vai Val Ile Met Gly Cys Tyr Ser Gly Asn Gly Gin 145 Val Val Phe Asn Gin Ile Phc Ser Ser 130 Ser Arg Lys Pro Asp Pro Asp Gly 100 Gly His Gin Thr Cys Leu Phe Sen Arg 85 Leu Asn Lys Giu Thr Lys Giu Glu Val Leu Leu Val Ile 135 Tyr Pro Lys 25 Phe Leu Ser Val Leu l05 Lys Ile Arg Tyr Leu Arg Leu Cys 75 Leu Ile Leu Sen Arg 155 Gly Ile Ser Leu Lys Val Glu Thn Met 140 Gly Gly Glu Pro Phe Phe Asp Glu Asp Asn 125 Lys Giu Sen Lys Ile Lys Leu Leu Ala Arg 110 Ala Thr Thr Ile Ser Ile Thr Glu Glu Arg Tyr Asp Lys Asn Leu Giu His Ser Asp. Leu Tyr His Leu Giu 160 Arg Ile WO 98/24475 PTU9/20 PCT[US97/22104 -258- 165 170 Ser Gly Asp Lys Lys Pro Asp Ser Asn Glu Giu Asn Phe 180 185 INFORMATION FOR SEQ ID NO:i74: SEQUENCE CHARACTERISTICS: LENGTH: 590 amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION .590 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:174: 175 Met Lys Ala Ile Lys Ile Leu Leu Ile Met Thr Leu 1 Ile Gly Thr Gly Ser Leu Asp Ser Val 145 Ser Tyr Giy Phe Leu 225 Sen Giu Thr Asp Giy Lys Ser Leu 130 Val Pro Tyr Met Tyr 210 Glu Val Leu 35 Giu Al a Ile Leu Phe 115 Lys Gly Tyr Gly Gly 195 Pro Asn Asn Thr Tnp Lys Leu Gin 100 Tyr Asp Ala Tyr Met 180 Met Asn Tyr 5 Arg Pro Gly Lys Gly Lys Ser Gin Tyr Arg 165 Tyr Tyr Met Met Ala Lys Ala Phe 70 Asn Asn Tyr Lys Leu 150 Sen Gly Asp Phe Tyr 230 Leu Ile Thr 55 Ser Phe Leu Ang Thr 135 Lys Asn Met Phe Phe 215 Ala Phe Val 40 Ala Al a Ang Lys Thr 120 Ala Lys Asn Tyr Tyr 200 Met Leu Asp 25 Asp Leu Leu Ala Tyr 105 Gly Gin Gin Tyr Gly 185 Asp Met Asp Lys Gly Tyr Glu 75 Al a Leu Tyr Met Glu 155 Asn Gly Tyr Val Glu 235 Asp Gly Ile Lys His Lys Ile Leu 140 Asn Sen Met Asp Gin 220 Glu Sen Sen Tyr Asn Met Leu Ile Pro 125 Ala Giu Tyr Tyr Gly 205 Asp Ile Leu Gin Lys Ala Arg Ang Ile 110 Leu Asp Lys Tyr Gly 190 Met Tyr Leu Asn Leu Ser Ala Phe Gin Ala Gly Leu Ala Ser 175 Met Tyr Leu Asp Al a Lys Asn Asn Asn Ala Arg Ile Ser Gin 160 Pro Tyr Gly Met His 240 WO 98/24475 PCTIUS97/22104 -259- Asp Ala Ser Ile Asn Gin Leu Asp 245 Asp Arg Ala Phe 305 Gin Gin Met Asp Asp 385 Val Asp Gin Asp Asp 465 Ala Gly Asp Asp Asp 545 Asn Asp Lys Asp Leu 290 His Ala Asp Glu Leu 370 Lys Gly Asp Thr Gin 450 His Asn Asp Thr Thr 530 Asp Asp Met Asp Pro 275 Val Thr Lys Gly Val 355 Lys Ala Asn Leu Pro 435 Gly Asn Asp Met Gly 515 Gly Met Asp Gly Asp 260 Lys Asn Lys Glu Ala 340 Arg Asp Leu Tyr Asn 420 Ile Gly Asp Thr Asn 500 Asn Asn Asn Met Asp 580 Lys Phe Leu Ala Leu 325 Ser Asp Gin Asp Leu 405 Asp Asn Asn Asp Pro 485 Asn Thr Thr Asn Gly 565 Met Ser Ser Asp Met 310 Asn Pro Lys Lys Ser 390 Asp Ala Asn Ala His 470 Thr Thr Asp Asn Ala 550 Asp Gly Ser Lys Asn 295 Pro His Asn Leu Gly 375 Val Gly Ile Met Leu 455 Met Asp Asp Asp Asp 535 Asn Met Asp Gin Asp 280 Ser Thr Leu Lys Asp 360 Leu Gin Ser Asn Asp 440 Ile Asp Asp Thr Met 520 Asp Asp Gly Met Thr Pro 265 Ile His Lys Val Ile 345 Asn Ser Gin Leu Asn 425 Asn Asn Thr Lys Gly 505 Ser Met Met Asp Gly 585 Pro 250 Ala Gin Met Ser Gly 330 Asp Asn Ser Leu Lys 410 Pro Thr Pro Asn Asp 490 Asn Asn Gly Asn Met 570 Gly Thr Asn Thr Leu Val 315 Gin Ser Leu Glu Ser 395 Ile Met His Asn Thr 475 Ala Thr Met Asn Asp 555 Asn Asp Asp Leu Asn Lys 300 Asp Ile Val Asn Gin 380 His Asp Gin Ala Asn 460 Thr Ser Asp Asn Ser 540 Asp Asp Met Asp Met Arg 285 Asp Ala Lys Val Gin 365 Gin Ser Gly Gin Asn 445 Ala Asp Gly Thr Asn 525 Asn Met Asp Gly Asp Ser 270 Leu Asn Ile Glu Asn 350 Leu Ala Ser Asp Pro 430 Asp Thr Thr Asn Gly 510 Gly Asp Gly Met Asn 590 Arg 255 Phe Asn Ser Thr Met.

335 Lys Asp Gin Asp Asp 415 Ala Ser Asn Ser Asn 495 Asn Asn Met Asn Gly 575 Asp Tyr Ser Leu Ser 320 Lys Ala Asn Val Val 400 Arg Gin Lys Asp Asn 480 Thr Thr Asp Gly Ser 560 Gly INFORMATION FOR SEQ ID NO:175: SEQUENCE CHARACTERISTICS: LENGTH: 195 amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein WO 98/24475 PCTI~S97/22104 -260- (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: miscfeature LOCATION 1...195 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:175: Leu Asn Leu Arg Leu Ala Gly Ala Ser Val Leu Thr Ala Cys Val Phe 1 5 10 Ser Gly Cys Phe Phe Leu Lys Met Phe Asp Lys Lys Leu Ser Ser Asn 20 25 Asp Trp His Ile Gin Lys Val Glu Met Asn His Gin Val Tyr Asp Ile 40 Glu Thr Met Leu Ala Asp Ser Ala Phe Arg Glu His Glu Glu Glu Gin 55 Asp Ser Ser Leu Asn Thr Ala Leu Pro Glu Asp Lys Thr Ala Ile Glu 70 75 Ala Lys Glu Gin Glu Gin Lys Glu Lys Arg Lys His Trp Tyr Glu Leu 90 Phe Lys Lys Lys Pro Lys Pro Lys Ser Ser Met Gly Glu Phe Val Phe 100 105 110 Asp Gin Lys Glu Asn Arg Ile Tyr Gly Lys Gly Tyr Cys Asn Arg Tyr 115 120 125 Phe Ala Ser Tyr Thr Trp Gin Gly Asp Arg His Ile Ala Ile Glu Asp 130 135 140 Ser Gly Ile Ser Arg Lys Val Cys Arg Asp Glu His Leu Met Ala Phe 145 150 155 160 Glu Leu Glu Phe Met Glu Asn Phe Lys Gly Asn Phe Ala Val Thr Lys 165 170 175 Gly Lys Asp Thr Leu Ile Leu Asp Asn Gin Lys Met Lys Ile Tyr Leu 180 185 190 Lys Thr Pro 195 INFORMATION FOR SEQ ID NO:176: SEQUENCE CHARACTERISTICS: LENGTH: 744 amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: p.otein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature WO 98/24475 PCT/US97/22104 -261- LOCATION 1...744 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:176: Met Leu Lys Leu Ala Ser Lys Thr Ile Cys Leu Ser Leu Ile Ser Ser 1 5 10 Phe Thr Ala Val Glu Ala Phe Gin Lys His Gin Lys Asp Gly Phe Phe 25 Ile Glu Ala Gly Phe Glu Thr Gly Leu Leu Gin Gly Thr Gin Thr Gin 35 40 Glu Gin Thr Ile Ala Thr Thr Gin Glu Lys Pro Lys Pro Lys Pro Lys 55 Pro Lys Pro Ile Thr Pro Gin Ser Thr Tyr Gly Lys Tyr Tyr Ile Ser 70 75 Gin Ser Thr Ile Leu Lys Asn Ala Thr Glu Leu Phe Ala Glu Asp Asn 90 Ile Thr Asn Leu Thr Phe Tyr Ser Gin Asn Pro Val Tyr Val Thr Ala 100 105 110 Tyr Asn Gin Glu Ser Ala Glu Glu Ala Gly Tyr Gly Asn Asn Ser Leu 115 120 125 Ile Met Ile Gin Asn Phe Leu Pro Tyr Asn Leu Asn Asn Ile Glu Leu 130 135 140 Ser Tyr Thr Asp Asp Gin Gly Asn Val Val Ser Leu Gly Val Ile Glu 145 150 155 160 Thr Ile Pro Lys Gin Ser Gin Ile Ile Leu Pro Ala Ser Leu Phe Asn 165 170 175 Asp Pro Gin Leu Asn Ala Asp Gly Phe Gin Gin Leu Gin Thr Asn Thr 180 185 190 Thr Arg Phe Ser Asp Ala Ser Thr Gin Asn Leu Phe Asn Lys Leu Ser 195 200 205 Lys Val Thr Thr Asn Leu Gin Met Thr Tyr Ile Asn Tyr Asn Gin Phe 210 215 220 Ser Ser Gly Asn Gly Ser Gly Ser Lys Pro Pro Cys Pro Pro Tyr Glu 225 230 235 240 Asn Gin Ala Asn Cys Val Ala Lys Val Pro Pro Phe Thr Ser Gin Asp 245 250 255 Ala Lys Asn Leu Thr Asn Leu Met Leu Asn Met Met Ala Val Phe Asp 260 265 270 Ser Lys Ser Trp Glu Asp Ala Val Leu Asn Ala Pro Phe Gin Phe Ser 275 280 285 Asp Asn Asn Leu Ser Ala Pro Cys Tyr Ser Asp Tyr Leu Thr Cys Val 290 295 300 Asn Pro Tyr Asn Asp Gly Leu Val Asp Pro Lys Leu Ile Ala Lys Asn 305 310 315 320 L-s Gly Asp Glu Tyr Asn Ile Glu Asn Gly Gin Thr Gly Ser Val Ile 325 330 335 Leu Thr Pro Gin Asp Val Ile Tyr Ser Tyr Arg Val Ala Asn Asn Ile 340 345 350 Tyr Val Asn Leu Leu Pro Thr Arg Gly Gly Asp Leu Gly Leu Gly Ser 355 360 365 Gin Tyr Gly Gly Pro Asn Gly Pro Gly Asp Asp Gly Thr Asn Phe Gly 370 375 380 Ala Leu Gly Ile Leu Ser Pro Phe Leu Asp Pro Glu Ile Leu Phe Gly 385 390 395 400 WO 98/24475 PCT/US97/22104 -262- Lys Glu Leu Asn Lys Val Ala Ile Met Gin Leu Arg Asp Ile Ile His 405 410 415 Glu Tyr Gly His Thr Leu Gly Tyr Thr His Asn Gly Asn Met Thr Tyr 420 425 430 Gin Arg Val Arg Met Cys Glu Glu Asn Asn Gly Pro Glu Glu Arg Cys 435 440 445 Gin Gly Gly Arg Ile Glu Gin Val Asp Gly Lys Glu Val Gin Val Phe 450 455 460 Asp Asn Gly His Glu Val Arg Asp Thr Asp Gly Ser Thr Tyr Asp Val 465 470 475 480 Cys Ser Arg Phe Lys Asp Lys Pro Tyr Thr Ala Gly Ser Tyr Pro Asn 485 490 495 Ser Ile Tyr Thr Asp Cys Ser Gin Val Pro Ala Gly Leu Ile Gly Val 500 505 510 Thr Ser Ala Val Trp Gin Gin Leu Ile Asp Gin Asn Ala Leu Pro Val 515 520 525 Asp Phe Thr Asn Leu Ser Ser Gin Thr Asn Tyr Leu Asn Ala Ser Leu 530 535 540 Asn Thr Gin Asp Phe Ala Thr Thr Met Leu Ser Ala Ile Ser Gin Ser 545 550 555 560 Leu Ser Ser Ser Lys Ser Ser Ala Thr Thr Tyr Arg Thr Ser Lys Thr 565 570 575 Ser Arg Pro Phe Gly Ala Pro Leu Leu Gly Val Asn Leu Lys Met Gly 580 585 590 Tyr Gin Lys Tyr Phe Asn Asp Tyr Leu Gly Leu Ser Ser Tyr Gly Ile 595 600 605 Ile Lys Tyr Asn Tyr Ala Gin Ala Asn Asn Glu Lys Ile Gin Gin Leu 610 615 620 Ser Tyr Gly Val Gly Met Asp Val Leu Phe Asp Phe Ile Thr Asn Tyr 625 630 635 640 Thr Asn Glu Lys Asn Pro Lys Ser Asn Leu Thr Lys Lys Val Phe Thr 645 650 655 Ser Ser Leu Gly Val Phe Gly Gly Leu Arg Gly Leu Tyr Asn Ser Tyr 660 665 670 Tyr Leu Leu Asn Gin Tyr Lys Gly Ser Gly Asn Leu Asn Val Thr Gly 675 680 685 Gly Leu Asn Tyr Arg Tyr Lys His Ser Lys Tyr Ser Ile Gly Ile Ser 690 695 700 Val Pro Leu Val Gin Leu Lys Ser Arg Ile Val Ser Ser Asp Gly Ala 705 710 715 720 Tyr Thr Asn Ser Ile Thr Leu Asn Glu Gly Gly Ser His Phe Lys Val 725 730 735 Phe Phe Asn Tyr Gly Trp Ile Phe 740 INFORMATION FOR SEQ ID NO:177: SEQUENCE CHARACTERISTICS: LENGTH: 529 amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein WO 98/24475 PCT[US97/22104 -263- (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: miscfeature LOCATION 1...529 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:177: Met Thr Tyr Ile Asn Tyr Asn Gin Phe Ser Ser Gly Asn Gly Ser Gly 1 5 10 Ser Lys Pro Pro Cys Pro Pro Tyr Glu Asn Gin Ala Asn Cys Val Ala 20 25 Lys Val Pro Pro Phe Thr Ser Gin Asp Ala Lys Asn Leu Thr Asn Leu 40 Met Leu Asn Met Met Ala Val Phe Asp Ser Lys Ser Trp Glu Asp Ala 55 Val Leu Asn Ala Pro Phe Gin Phe Ser Asp Asn Asn Leu Ser Ala Pro 70 75 Cys Tyr Ser Asp Tyr Leu Thr Cys Val Asn Pro Tyr Asn Asp Gly Leu 90 Val Asp Pro Lys Leu Ile Ala Lys Asn Lys Gly Asp Glu Tyr Asn Ile 100 105 110 Glu Asn Gly Gin Thr Gly Ser Val Ile Leu Thr Pro Gin Asp Val Ile 115 120 125 Tyr Ser Tyr Arg Val Ala Asn Asn Ile Tyr Val Asn Leu Leu Pro Thr 130 135 140 Arg Gly Gly Asp Leu Gly Leu Gly Ser Gin Tyr Gly Gly Pro Asn Gly 145 150 155 160 Pro Gly Asp Asp Gly Thr Asn Phe Gly Ala Leu Gly Ile Leu Ser Pro 165 170 175 Phe Leu Asp Pro Glu Ile Leu Phe Gly Lys Glu Leu Asn Lys Val Ala 180 185 190 Ile Met Gin Leu Arg Asp Ile Ile His Glu Tyr Gly His Thr Leu Gly 195 200 205 Tyr Thr His Asn Gly Asn Met Thr Tyr Gin Arg Val Arg Met Cys Glu 210 215 220 Glu Asn Asn Gly Pro Glu Glu Arg Cys Gin Gly Gly Arg Ile Glu Gin 225 230 235 240 Val Asp Gly Lys Glu Val Gin Val Phe Asp Asn Gly His Glu Val Arg 245 250 255 Asp Thr Asp Gly Ser Thr Tyr Asp Val Cys Ser Arg Phe Lys Asp Lys 260 265 270 Pro Tyr Thr Ala Gly Ser Tyr Pro Asn Ser i1c Tyr Thr Asp Cys Ser 275 280 285 Gin Val Pro Ala Gly Leu Ile Gly Val Thr Ser Ala Val Trp Gin Gin 290 295 300 Leu Ile Asp Gin Asn Ala Leu Pro Val Asp Phe Thr Asn Leu Ser Ser 305 310 315 320 Gin Thr Asn Tyr Leu Asn Ala Ser Leu Asn Thr Gin Asp Phe Ala Thr 325 330 335 Thr Met Leu Ser Ala Ile Ser Gin Ser Leu Ser Ser Ser Lys Ser Ser WO 98/24475 WO 9824475PCTIUS97/22104 264 Al a Leu Tyr 385 Ala Val Ser Gly Gly 465 His Ser Asn Phe Thr Leu 370 Leu Asn Leu Asn Leu 450 Ser Ser Arg Giu Thr 355 Gly Gly Asn Phe Leu 435 Arg Gly Lys Ile Gly 515 340 Tyr Val Leu Glu Asp 420 Thr Gly Asn Tyr Val 500 Gly Thr Leu Ser 390 Ile Ile Lys Tyr Asn 470 Ile Ser His Ser Lys 375 Tyr Gin Thr Val Asn 455 Val Giy Asp Phe Lys 360 Met Gly Gin Asn Phe 440 Ser Thr Ile Gly Lys 520 345 Thr Gly Ile Leu Tyr 425 Thr Tyr Giy Ser Ala 505 Val Ser Tyr Ile Ser 410 Thr Ser Tyr Gly Val 490 Tyr Phe Arg Gin Lys 395 Tyr Asn Ser Leu Leu 475 Pro Thr Phe Pro Lys 380 Tyr Gly Giu Leu Leu 460 Asn Leu Asn Asn 350 Giy Phe Tyr Giy Asn 430 Val Gin Arg Gin Ile 510 Gly Al a Asn Ala Met 415 Pro Phe Tyr Tyr Leu 495 Thr Trp Pro Asp Gin 400 Asp Lys Gly Lys Lys 480 Lys Leu Ile INFORMATION FOR SEQ ID NO:178: SEQUENCE CHARACTERISTICS: LENGTH: 187 amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Heiicobacter pyloni (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...187 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:178: Leu Gly Cys Val Ser Met Thr Leu Gly Ile Asp Glu Ala Gly Arg Gly 1 5 10 Cys Leu Ala Gly Ser Leu Phe Val Ala Gly Val Val Cys Asn Glu Lys 20 25 Ile Ala Leu Glu Phe Leu Lys Met Gly Leu Lys Asp Ser Lys Lys Leu 40 Ser Pro Lys Lys Arg Phe Phe Leu Glu Asp Lys Ile Lys Thr His Gly 55 WO 98/24475 PCTIS97/22104 -265- Glu Val Gly Phe Phe Val Val Lys Lys Ser Ala Asn Glu Ile Asp His 70 75 Leu Gly Leu Gly Ala Cys Leu Lys Leu Ala Ile Glu Glu Ile Val Glu 90 Asn Gly Cys Ser Leu Ala Asn Glu Ile Lys Ile Asp Gly Asn Thr Ala 100 105 110 Phe Gly Leu Asn Lys Arg Tyr Pro Asn Ile Gin Thr Ile Ile Lys Gly 115 120 125 Asp Glu Thr Ile Ala Gin Ile Ala Met Ala Ser Val Leu Ala Lys Ala 130 135 140 Ser Lys Asp Arg Glu Met Leu Glu Leu His Ala Leu Phe Lys Glu Tyr 145 150 155 160 Gly Trp Asp Lys Asn Cys Gly Tyr Gly Thr Lys Gin His Ile Glu Ala 165 170 175 Ile Asn Lys Leu Gly Ala Thr Leu Ser Ser Ala 180 185 INFORMATION FOR SEQ ID NO:179: SEQUENCE CHARACTERISTICS: LENGTH: 204 amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...204 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:179: Met Thr Leu Gly Ile Asp Glu Ala Gly Arg Gly Cys Leu Ala Gly Ser 1 5 10 Leu Phe Val Ala Gly Val Val Cys Asn Glu Lys Ile Ala Leu Glu Phe 25 Leu Lys Met Gly Leu Lys Asp Ser Lys Lys Leu Ser Pro Lys Lys Arg 40 Phe Phe Leu Glu Asp Lys Ile Lys Thr His Gly Glu Val Gly Phe Phe 50 55 Val Val Lys Lys Ser Ala Asn Glu Ile Asp His Leu Gly Leu Gly Ala 70 75 Cys Leu Lys Leu Ala Ile Glu Glu Ile Val Glu Asn Gly Cys Ser Leu 90 Ala Asn Glu Ile Lys Ile Asp Gly Asn Thr Ala Phe Gly Leu Asn Lys 100 105 110 Arg Tyr Pro Asn Ile Gin Thr Ile Ile Lys Gly Asp Glu Thr Ile Ala 115 120 125 Gin Ile Ala Met Ala Ser Val Leu Ala Lys Ala Ser Lys Asp Arg Glu WO 98/24475 PCT/US97/22104 -266- 130 135 140 Met Leu Glu Leu His Ala Leu Phe Lys Glu Tyr Gly Trp Asp Lys Asn 145 150 155 160 Cys Gly Tyr Gly Thr Lys Gin His Ile Glu Ala Ile Asn Lys Leu Gly 165 170 175 Ala Thr Pro Phe His Arg His Ser Phe Thr Leu Lys Asn Arg Ile Leu 180 185 190 Asn Pro Lys Leu Leu Glu Val Glu Gin Arg Leu Val 195 200 INFORMATION FOR SEQ ID NO:180: SEQUENCE CHARACTERISTICS: LENGTH: 192 amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...192 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:180: Met Asn Ala Leu Lys Lys Leu Ser Phe Cys Ala Leu Leu Ser Leu Gly 1 5 10 Leu Phe Ala Gin Thr Val His Ala Gin His Leu Lys Asp Thr Ile Asn 25 Tyr Pro Asp Trp Leu Lys Ile Asn Leu Phe Asp Lys Lys Asn Pro Pro 40 Asn Gin Tyr Val Gly Ser Ala Ser Ile Ser Gly Lys Arg Asn Asp Phe 55 Tyr Ser Asn Tyr Ile Pro Tyr Asp Asp Lys Leu Pro Pro Glu Lys Asn 65 70 75 Ala Glu Glu Ile Ala Leu Leu Arg Ala Arg Met Asn'Ala Tyr Ser Thr 90 Leu Glu Ser Ala Leu Leu Thr Lys Met Cys Asn Arg Ile Val Lys Ala 100 105 110 Leu Gin Val Lys Asn Asn Val Ile Ser His Leu Phe Gly Phe Val Asp 115 120 125 Phe Leu Thr Ser Lys Ser Ile Leu Ala Lys Arg Phe Val Asp Thr Thr 130 135 140 Asn His Arg Val Tyr Val Met Val Gin Phe Pro Phe Ile Gin Pro Glu 145 150 155 160 Asp Leu Ile Ala Tyr Phe Lys Ala Lys Arg Ile Asp Leu Ser Leu Ala 165 170 175 Ser Ala Thr Asn Leu Ser Ala Ile Leu Asn Lys Ala Leu Phe His Leu 180 185 190 WO 98/24475 PCT/US97/22104 -267- INFORMATION FOR SEQ ID NO:181: SEQUENCE CHARACTERISTICS: LENGTH: 86 amino acids TYPE: amino acid TOPOLOGYi linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...86 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:181: Met Asn Ala Leu Lys Lys Leu Ser Phe Cys Ala Leu Leu Ser Leu Gly 1 5 10 Leu Phe Ala Gin Thr Val His Ala Gin His Leu Lys Asp Thr Ile Asn 20 25 Tyr Pro Asp Trp Leu Lys Ile Asn Leu Phe Asp Lys Lys Asn Pro Pro 40 Asn Gin Tyr Val Gly Ser Ala Ser Ile Ser Gly Lys Arg Asn Asp Phe 55 Tyr Ser Asn Tyr Ile Pro Tyr Asp Asp Lys Leu Pro Pro Glu Arg Thr 70 75 Leu Lys Lys Ser Leu Phe INFORMATION FOR SEQ ID NO:182: SEQUENCE CHARACTERISTICS: LENGTH: 75 amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...75 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:182: WO 98/24475 PTU9/20 PCTfUS97/22104 -268- Leu Lys Ile Leu Thr Leu Phe Leu Ile Gly Leu Asn Ala Leu Phe Ala 1 5 10 Leu Asp Leu Asn Ala Leu Lys Thr Giu Ile Lys Glu Thr Tyr Leu Lys 25 Glu Tyr Lys Asp Leu Lys Leu Glu Ile Glu Thr Ile Asn Leu Glu Ile 40 Pro Giu Arg Phe Ser His Ala Ser Ile Leu Ser Tyr Glu Leu Asn Ala 55 Ser Asn Lys Leu Lys Lys Asp Giy Ser Cys Phe 65 70 INFORMATION FOR SEQ ID NO:i83: SEQUENCE CHARACTERISTICS: LENGTH: 211. amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE:. protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION,,'i.. .211 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:183: Met Phe Ser*.lie Ile Le4'Gly Gly Gly Gly Gly Asn 1 Leu Thr Tyr Phe Leu Gin Asn Arg Giu 145 Leu Met Trp Ser Thr Asn Gin Met Leu Lys Gly Gin Gin 20 Phe Arg Al a Met Arg i00 Ile Leu Ile Ile Thr Phe Lys Ser Asn 70 Phe Ile His Vai Leu 150 Phe Gin Lys Asp Gin Leu Phe Thr Tyr Leu 135 Pro Asp Giy Leu Ala 40 Asn Asn Tyr Pro Phe i2 0 Vai Leu Phe Val Gly 25 Leu Gin Pro Arg Lys 105 Thr Arg Lys Met Val Leu Gin Vai Phe 75 Lys Giu Leu Ile Thr 155 Thr Tyr Phe Giy Leu Thr Ser Ile Leu Asp 140 Ala Leu Cys Thr Giu Gin Gin Trp Trp Lys Asn 125 Lys Lys Ile Asp Pro Ile Asp Thr Ser Tyr Asn 110 Ala Thr Thr Asn Ala Cys is Glu Tyr Thr Leu Ala Lys Leu Phe Gin Ala 175 Lys Gly Lys Asp Gly Gly Gly Ile Lys Arg Ser 160 Leu Ile WO 98/24475 PCT/US97/22104 -269- 180 185 190 Gin Ala Thr Lys Glu Val Ile Ser Gin Glu Thr Pro Ile Gin Lys Asp 195 200 205 Ser Leu Phe 210 INFORMATION FOR SEQ ID NO:184: SEQUENCE CHARACTERISTICS: LENGTH: 406 amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...406 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:184: Val Ile Gly Pro Leu Ser Ser Gin Leu Asn Ala Ile Lys Trp Gly Glu 1 5 10 Phe Lys Leu Gly Asp Leu Phe Glu Ala Ser Asn Gly Asp Phe Asp Ile 20 25 Gin Lys Arg His Ile Asn His Lys Gly Glu Phe Val Ile Thr Ala Gly 40 Leu Ser Asn Asn Gly Val Leu Gly Gln.Ser Asp Ile Lys Ala Lys Val 55 Phe Glu Ser His Thr Ile Thr Ile Asp Met Phe Gly Cys Ala Phe Tyr 70 75 Arg Ser Phe Ala Tyr Lys Met Val Thr His Ala Arg Val Phe Ser Leu 90 Lys Pro Lys Phe Glu Ile Asn His Lys Ile Gly Leu Phe Leu Ser Thr 100 105 110 Leu Phe Phe Gly Tyr His Lys Lys Phe Gly Tyr Glu Asn Met Cys Ser 115 120 125 Trp Ala Lys Ile Lys Asn Asp Lys Val Ile Leu Pro Leu Lys Pro Thr 130 135 140 Ala Asn Thr Gin Thr Leu Glu Gly Ile Asp Phe Asp Phe Met Glu Lys 145 150 155 160 Phe Ile Ala Glu Leu Glu Gin Cys Arg Leu Ala Glu Leu Gin Ala Tyr 165 170 175 Leu Lys Ala Thr Gly Leu Glu Asn Thr Thr Leu Ser Asn Asp Glu Glu 180 185 190 Asn Ala Leu Asn Val Phe Asn Asn Ser Gly Gly Gly Gly Gly Asn Thr 195 200 205 Pro Cys Gly Leu Thr Trp Gin His Phe Lys Leu Gly Asp Leu Phe Glu 210 215 220 WO 98/24475 PCT/US97/22104 -270- Ile Glu Lys Thr Leu Ser Phe Asn Lys Asp Ala Leu Thr Gin Gly Gin 225 230 235 240 Asp Tyr Asp Tyr Ile Thr Arg Thr Ser Gin Asn Gin Gly Val Leu Gin 245 250 255 Thr Thr Gly Phe Val Asn Ala Glu Asn Leu Asn Pro Pro Phe Thr Trp 260 265 270 Ser Leu Gly Leu Leu .Gn Met Asp Phe Phe Tyr Arg Lys Lys Ser Trp 275 280 285 Tyr Ala Gly Gin Phe Met Arg Lys Ile Thr Pro Lys Thr Glu Ile Lys 290 295 300 Asn Lys Ile Asn Ser Arg Ile Ala His Tyr Phe Thr Thr Leu Leu Asn 305 310 315 320 Ala Leu Lys Arg Pro Leu Leu Ser Val Leu Val Arg Asp Ile Asp Lys 325 330 335 Thr Phe Arg Glu Gin Lys Ile Gin Leu Pro Leu Lys Pro Thr Ala Lys 340 345 350 Thr Gin Ser Leu Asp Gly Ile Asp Phe Asp Phe Met His Thr Leu Ile 355 360 365 Asn Ala Leu Met Lys Gin Thr Ile Gin Gly Val Val Gin Tyr Cys Asp 370 375 380 Ala Lys Ile Gin Ala Thr Lys Glu Val Ile Ser Gin Glu Thr Pro Ile 385 390 395 400 Gin Lys Asp Ser Leu Phe 405 INFORMATION FOR SEQ ID NO:185: SEQUENCE CHARACTERISTICS: LENGTH: 275 amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...275 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:185: Met Ser Lys Ser Leu Tyr Gin Thr Leu Asn Val Ser G.d Asn Ala Ser 1 5 10 Gin Asp Glu Ile Lys Lys Ser Tyr Arg Arg Leu Ala Arg Gin Tyr His 25 Pro Asp Leu Asn Lys Thr Lys Glu Ala Glu Glu Lys Phe Lys Glu Ile 40 Asn Ala Ala Tyr Glu Ile Leu Ser Asp Glu Glu Lys Arg Arg Gin Tyr 55 Asp Gin Phe Gly Asp Asn Met Phe Gly Gly Gin Asn Phe Ser Asp Phe WO 98/24475 PCTftJS97/22104 -271- 70 75 Ala Arg Ser Arg Gly Pro Ser Glu Asp Leu Asp Asp Ile Leu Ser Ser 90 Ile Phe Gly Lys Gly Gly Phe Ser Gin Arg Phe Ser Gin Asn Ser Gin 100 105 110 Gly Phe Ser Gly Phe Asn Phe Ser Asn Phe Ala Pro Glu Asn Leu Asp 115 120 125 Val Thr Ala Ile Leu Asn Val Ser Val Leu Asp Thr Leu Leu Gly Asn 130 135 140 Lys Lys Gin Val Ser Val Asn Asn Glu Thr Phe Ser Leu Lys Ile Pro 145 150 155 160 Ile Gly Val Glu Glu Gly Glu Lys Ile Arg Val Arg Asn Lys Gly Lys 165 170 175 Met Gly Arg Thr Gly Arg Gly Asp Leu Leu Leu Gin Ile His Ile Glu 180 185 190 Glu Asp Glu Met Tyr Arg Arg Glu Lys Asp Asp Ile Ile Gin Ile Phe 195 200 205 Asp Leu Pro Leu Lys Thr Ala Leu Phe Gly Gly Lys Ile Glu Ile Ala 210 215 220 Thr Trp His Lys Thr Leu Thr Leu Thr Ile Pro Pro Asn Thr Lys Ala 225 230 235 240 Met Gin Lys Phe Arg Ile Lys Asp Lys Gly Ile Lys Ser Arg Lys Thr 245 250 255 Ser His Val Gly Asp Cys Ile Ala Ser Ser Phe Asp Leu Leu Lys Leu 260 265 270 Lys Arg Phe 275 INFORMATION FOR SEQ ID NO:186: SEQUENCE CHARACTERISTICS: LENGTH: 278 amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...778 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:186: Met Ser Lys Ser Leu Tyr Gin Thr Leu Asn Val Ser Glu Asn Ala Ser 1 5 10o Gin Asp Glu Ile Lys Lys Ser Tyr Arg Arg Leu Ala Arg Gin Tyr His 25 Pro Asp Leu Asn Lys Thr Lys Glu Ala Glu Glu Lys Phe Lys Glu Ile 40 WO 98/24475 PCT/US97/22104 -272- Asn Ala Ala Tyr Glu Ile Leu Ser Asp Glu Glu Lys Arg Arg Gin Tyr 55 Asp Gin Phe Gly Asp Asn Met Phe Gly Gly Gin Asn Phe Ser Asp Phe 70 75 Ala Arg Ser Arg Gly Pro Ser Glu Asp Leu Asp Asp Ile Leu Ser Ser 90 Ile Phe Gly Lys Gly Gly Phe Ser Gin Arg Phe Ser Gin Asn Ser Gin 100 105 110 Gly Phe Ser Gly Phe Asn Phe Ser Asn Phe Ala Pro Glu Asn Leu Asp 115 120 125 Val Thr Ala Ile Leu Asn Val Ser Val Leu Asp Thr Leu Leu Gly Asn 130 135 140 Lys Lys Gin Val Ser Val Asn Asn Glu Thr Phe Ser Leu Lys Ile Pro 145 150 155 160 Ile Gly Val Glu Glu Gly Glu Lys Ile Arg Val Arg Asn Lys Gly Lys 165 170 175 Met Gly Arg Thr Gly Arg Gly Asp Leu Leu Leu Gin Ile His Ile Glu 180 185 190 Glu Asp Glu Met Tyr Arg Arg Glu Lys Asp Asp Ile Ile Gin Ile Phe 195 200 205 Asp Leu Pro Leu Lys Thr Ala Leu Phe Gly Gly Lys Ile Glu Ile Ala 210 215 220 Thr Trp His Lys Thr Leu Thr Leu Thr Ile Pro Pro Asn Thr Lys Ala 225 230 235 240 Met Gin Lys Phe Arg Ile Lys Asp Lys Gly Ile Lys Ser Arg Lys Thr 245 250 255 Ser His Val Gly Asp Cys Ile Ala Ser Ser Phe Asp Leu Pro Lys Ile 260 265 270 Glu Thr Leu Leu Met Ser 275 INFORMATION FOR SEQ ID NO:187: SEQUENCE CHARACTERISTICS: LENGTH: 232 amino acids TYPE: amino acid iD) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...232 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:187: Val Val Gin Lys Phe Asn Phe Tyr Lys Thr Gly Gly Met Arg Leu Lys 1 5 10 His Phe Lys Thr Phe Leu Phe Ile Thr Met Ala Val Ile Val Ile Gly WO 98/24475 WO 9824475PCTIUS97/22104 273- Thr Gly Cys'Ala Asn Lys Lys Lys Ala Leu Asn Met Ile Lys Giu 145 Tyr Phe Lys Asp Trp 225 Ile Glu Ser Lys Lys Leu 130 Phe Pro Ile Lys Giu 210 Tyr Phe Thr Pro Lys Arg 115 Gin Ile Asn Leu Arg 195 Thr Val Trp Ala Leu Lys 100 Phe Ser Ser Ser Gly 180 His Leu Leu Gin Asn 70 Pro Tyr Thr Tyr Ser 150 Tyr Asn Pro Lys Phe 230 Gly Tyr Giu Val Lys Tyr 135 Ile Arg Giu Giu Giu 215 Asp 40 Ile Tyr Ala Leu Asp 120 Ala Val Pro Leu Gly 200 Thr Trp 25 Lys Leu Ser Met Ala 105 Asn Phe Ser Tyr Asn 185 Val Lys Lys Arg Ser Leu Ser Val Lys Leu Val1 170 Arg Lys Pro Asp Giu.

Leu, 75 Ala Phe Asp Asn Gly 155 Giu Al a Arg Lys Tyr Leu Ser Gly Phe Leu 125 Ser Phe Met Ala Leu 205 Ser Asn Phe Glu Gin Asp 110 Thr Lys Ile Gin Asn 190 Giu His Lys Ala His Ala Giu Phe Asp Giu Ile 175 Val1 Arg Met Pro Asn Ile His Tyr Leu Gin Lys 160 Lys Tyr Ile Pro INFORMATION FOR SEQ ID NO:188: SEQUENCE CHARACTERISTICS: LENGTH: 114 amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION .114 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:188: Met Arg Phe Leu Asn Asn Lys His Arg Giu. Lys Gly Leu Lys Ala Glu 1 5 10 Giu Glu Ala Cys Gly Phe Leu Lys Thr Leu Gly Phe Glu Met Ile Glu 25 Arg Asn Phe Phe Ser Gin Phe Gly Giu Ile Asp Ile Ile Ala Leu Lys 40 WO 98/24475 PCTIUS97/22104 -274- Lys Gly Val Leu His Phe Ile Glu Val Lys Ser Gly Glu Asn Phe Asp 55 Pro Ile Tyr Ala Ile Thr Pro Ser Lys Leu Lys Lys Met Ile Lys Thr 70 75 Ile Arg Cys Tyr Leu Ser Gin Lys Asp Pro Asn Ser Asp Phe Cys Ile 90 Asp Ala Leu Ile Val Lys Asn Gly Lys Phe Glu Leu Leu Glu Asn Ile 100 105 110 Thr Phe INFORMATION FOR SEQ ID NO:189: SEQUENCE CHARACTERISTICS: LENGTH: 101 amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: miscfeature LOCATION 1...101 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:189: Met Gly Ser Ile Gly Ala Met Thr Lys Gly Ser Ser Asp Arg Tyr Phe 1 5 10 Gin Glu Gly Val Ala Ser Glu Lys Leu Val Pro Glu Gly Ile Glu Gly 20 25 Arg Val Pro Tyr Arg Gly Lys Val Ser Asp Met Ile Phe Gin Leu Val 40 Gly Gly Val Arg Ser Ser Met Gly Tyr Gin Gly Ala Lys Asn Ile Leu 55 Glu Leu Tyr Gin Asn Ala Glu Phe Val Glu Ile Thr Ser Ala Gly Leu 70 75 Lys Lys Ser His Val His Gly Val Asp Ile Thr Lys Glu Ala Pro Asn 90 Ile Met Gly Glu Phe 100 INFORMATION FOR SEQ ID NO:190: SEQUENCE CHARACTERISTICS: LENGTH: 481 amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein WO 98/24475 PCT/US97/22104 275 (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: miscfeature LOCATION 1...481 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:190: Met Arg Ile Leu Gin Arg Ala Leu Thr Phe Glu Asp Val Leu Met Val 1 5 10 Pro Arg Lys Ser Ser Val Leu Pro Lys Asp Val Ser Leu Lys Ser Arg 25 Leu Thr Lys Asn Ile Gly Leu Asn Ile Pro Phe Ile Ser Ala Ala Met 40 Asp Thr Val Thr Glu His Lys Thr Ala Ile Ala Met Ala Arg Leu Gly 50 55 Gly Ile Gly Ile Val His Lys Asn Met Asp Ile Gin Thr Gin Val Lys 70 75 Glu Ile Thr Lys Val Lys Lys Ser Glu Ser Gly Val Ile Asn Asp Pro 90 Ile Phe Ile His Ala His Arg Thr Leu Ala Asp Ala Lys Val Ile Thr 100 105 110 Asp Asn Tyr Lys Ile Ser Gly Val Pro Val Val Asp Asp Lys Gly Leu 115 120 125 Leu Ile Gly Ile Leu Thr Asn Arg Asp Val Arg Phe Glu Thr Asp Leu 130 135 140 Ser Lys Lys Val Gly Asp Val Met Thr Lys Met Pro Leu Val Thr Ala 145 150 155 160 His Val Gly Ile Ser Leu Asp Glu Ala Ser Asp Leu Met His Lys His 165 170 175 Lys Ile Glu Lys Leu Pro Ile Val Asp Lys Asp Asn Val Leu Lys Gly 180 185 190 Leu Ile Thr Ile Lys Asp Ile Gin Lys Arg Ile Glu Tyr Pro Glu Ala 195 200 205 Asn Lys Asp Asp Phe Gly Arg Leu Arg Val Gly Ala Ala Ile Gly Val 210 215 220 Gly Gin Leu Asp Arg Ala Glu Met Leu Val Lys Ala Gly Val Asp Ala 225 230 235 240 Leu Val Leu Asp Ser Ala His Gly His Ser Ala Asn Ile Leu His Thr 245 250 255 Leu Glu Glu Ile Lys Lys Ser Leu Val Val Asp Val Ile Val Gly Asn 260 265 270 Val Val Thr Lys Glu Ala Thr Ser Asp Leu Ile Ser Ala Gly Ala Asp 275 280 285 Ala Val Lys Val Gly Ile Gly Pro Gly Ser Ile Cys Thr Thr Arg Ile 290 295 300 Val Ala Gly Val Gly Met Pro Gin Val Ser Ala Ile Asp Asn Cys Val 305 310 315 320 Glu Val Ala Ser Lys Phe Asp Ile Pro Val Ile Ala Asp Gly Gly Ile 325 330 335 WO 98/24475 PCT/US97/22104 -276- Arg Tyr Ser Gly Asp Val Ala Lys Ala Leu Ala Leu Gly Ala Ser Ser 340 345 350 Val Met Ile Gly Ser Leu Leu Ala Gly Thr Glu Glu Ser Pro Gly Asp 355 360 365 Phe Met Ile Tyr Gin Gly Arg Gln Tyr Lys Ser Tyr Arg Gly Met Gly 370 375 380 Ser Ile Gly Ala Met Thr Lys Gly Ser Ser Asp Arg Tyr Phe Gln Glu 385 390 395 400 Gly Val Ala Ser Glu Lys Leu Val Pro Glu Gly Ile Glu Gly Arg Val 405 410 415 Pro Tyr Arg Gly Lys Val Ser Asp Met Ile Phe Gin Leu Val Gly Gly 420 425 430 Val Arg Ser Ser Met Gly Tyr Gin Gly Ala Lys Asn Ile Leu Glu Leu 435 440 445 Tyr Gin Asn Ala Glu Phe Val Glu Ile Thr Ser Ala Gly Leu Lys Glu 450 455 460 Ser His Val His Gly Val Asp Ile Thr Lys Glu Ala Pro Asn Tyr Tyr 465 470 475 480 Gly INFORMATION FOR SEQ ID NO:191: SEQUENCE CHARACTERISTICS: LENGTH: 204 amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...204 (xi) SEQUENCE DESCRIPTION:.SEQ ID NO:191: Met Gin Gly Phe Leu Leu Gin Thr Gin Ser Ile Arg Asp Glu Asp Leu 1 5 10 Ile Val His Val Leu Thr Lys Asn Gin Leu Lys Thr Leu Tyr Arg Phe 20 25 Tyr Gly Lys Arg His Ser Val Leu Asn Val Gly Arg Lys Ile Asp Phe 40 Glu Glu Glu Asn Asp Asp Lys Phe Leu Pro Lys Leu Arg Asn Ile Leu 55 His Leu Gly Tyr Ile Trp Glu Arg Glu Met Glu Arg Leu Phe Phe Trp 70 75 Gin Arg Phe Cys Ala Leu Leu Phe Lys His Leu Glu Gly Val His Ser 90 Leu Asp Ser Ile Tyr Phe Asp Thr Leu Asp Asp Gly Ala Ser Lys Leu WO 98/24475 PCT[~S97/22104 -277- 100 105 110 Ser Lys Gin His Pro Leu Arg Val Ile Leu Glu Met Tyr Ala Val Leu 115 120 125 Leu Asn Phe Glu Gly Arg Leu Gin Ser Tyr Asn Ser Cys Phe Leu Cys 130 135 140 Asp Ala Lys Leu Glu Arg Ser Val Ala Leu Ala Gin Gly Phe Ile Leu 145 150 155 160 Ala His Pro Ser Cys Leu Lys Ala Lys Ser Leu Asp Leu Glu Lys Ile 165 170 175 Gin Ala Phe Phe Arg Thr Gin Ser Thr Ile Asp Leu Glu Thr Glu Glu 180 185 190 Val Glu Glu Leu Trp Arg Thr Leu Asn Leu Gly Phe 195 200 INFORMATION FOR SEQ ID NO:192: SEQUENCE CHARACTERISTICS: LENGTH: 82 amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...82 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:192: Met Gly Val Gly Arg Val Gly Asn Met Ala Leu Leu Ala Cys Ala Gly 1 5 10 Pro Met Gly Ile Gly Ala Ile Ala Ile Ala Ile Asn Gly Gly Arg Gin 25 Arg Ser Arg Met Leu Val Val Asp Ile Asp Asp Lys Arg Leu Glu Gin 35 40 Val Gin Lys Met Leu Pro Gly Asn Trp Arg Pro Val Thr Ala Leu Ser 55 Trp Cys Leu Cys Ile Pro Lys Arg Gly Ala Ile Arg Ala Arg Cys Cys 70 75 Glu Arg INFORMATION FOR SEQ ID NO:193: SEQUENCE CHARACTERISTICS: LENGTH: 67 amino acids TYPE: amino acid TOPOLOGY: linear WO 98/24475 PCTIUS97/22104 -278- (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...67 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:193: Leu Ser Gly Thr Ala Val Ser Cys Arg Cys Thr Cys Arg Ile Gin Leu 1 5 10 Val Leu Val Arg Thr Ser Ile Pro Val Val Ile Gly Cys Ser Cys Pro 25 Phe Leu Ser Ser Ile Gly Phe Thr Thr Gly Thr His Gin Ser Pro Val 40 Lys Arg Cys Gly Val Asn Ala Gly Lys Thr Pro Ser Lys Lys His Leu 55 His Leu Asn INFORMATION FOR SEQ ID NO:194: SEQUENCE CHARACTERISTICS: LENGTH: 114 amino acids TYPE: amino acid TOPOLOGY: linear (ii) MOLECULE TYPE: protein (iii) HYPOTHETICAL: YES (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...114 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:194: Val Trp Leu Ala Ala Leu Gly Phe Leu Ile Thr Ala Val Gly Leu Pro 1 5 .0 Val Ile Thr Val Ile Ala Leu Ala Lys Val Gly Gly Ser Ser Thr Pro 25 Ser Ala Ile Arg Ser Ala Gly Met Pro Ala Ala Cys Trp Arg Arg Ser 35 40 Ala Thr Trp Arg Ser Ala Arg Cys Ser Pro Phe Arg Ala Pro Pro Arg 55 Cys Pro Ser Lys Val Ser Val Val Pro Leu Leu Gly Glu Glu Ala Ala 70 75 WO 98/24475 PCT/US97/22104 -279- Arg Arg Cys Ser Ser Thr Ala Trp Arg Thr Ser Ser Ser Pro Trp Pro 90 Ser Pro Ser Thr Pro Val Ala Cys Trp Thr Pro Ser Asp Ala Ser Ser 100 105 110 Pro Arg INFORMATION FOR SEQ ID NO:195: SEQUENCE CHARACTERISTICS: LENGTH: 20 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...20 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:195: TATACCATGG TGGGCGCTAA INFORMATION FOR SEQ ID NO:196: SEQUENCE CHARACTERISTICS: LENGTH: 23 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc_feature LOCATION 1...23 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:196: WO 98/24475 PCT/US97/22104 -280- ATGAATTCGA GTAAGGATTT TTG 23 INFORMATION FOR SEQ ID NO:197: SEQUENCE CHARACTERISTICS: LENGTH: 22 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...22 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:197: TTAACCATGG TGAAAAGCGA TA 22 INFORMATION FOR SEQ ID NO:198: SEQUENCE CHARACTERISTICS: LENGTH:.23 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...23 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:198: TAGAATTCGC ATAACGATCA ATC 23 INFORMATION FOR SEQ ID NO:199: WO 98/24475 PCT/US97/22104 -281- SEQUENCE CHARACTERISTICS: LENGTH: 22 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: miscfeature LOCATION 1...22 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:199: ATATCCATGG TGAGTTTGAT GA 22 INFORMATION FOR SEQ ID NO:200: SEQUENCE CHARACTERISTICS: LENGTH: 25 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...25 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:200: ATGAATTCAA TTTTTTATTT TGCCA INFORMATION FOR SEQ ID NO:201: SEQUENCE CHARACTERISTICS: LENGTH: 21 base pairs TYPE: nucleic acid WO 98/24475 PCTI/US97/22104 -282- STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...21 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:201: AATTCCATGG TGGGGGCTAT G 21 INFORMATION FOR SEQ ID NO:202: SEQUENCE CHARACTERISTICS: LENGTH: 23 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...23 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:202: ATGAATTCTC GATAGCCAAA ATC 23 INFORMATION FOR SEQ ID N,:203: SEQUENCE CHARACTERISTICS: LENGTH: 25 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) WO 98/24475 PCTIUS97/22104 -283 (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: miscfeature LOCATION 1...25 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:203: AATTCCATGG TGCATAACTT CCATT INFORMATION FOR SEQ ID NO:204: SEQUENCE CHARACTERISTICS: LENGTH: 25 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: miscfeature LOCATION 1...25 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:204: AAGAATTCTC TAGCATCCAA ATGGA INFORMATION FOR SEQ ID NO:205: SEQUENCE CHARACTERISTICS: LENGTH: 24 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO WO 98/24475 PCT/UJS97/22104 -284- (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: miscfeature LOCATION 1...24 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:205: ATTTCCATGG TCATGTCTCA TATT 24 INFORMATION FOR SEQ ID NO:206: SEQUENCE CHARACTERISTICS: LENGTH: 23 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...23 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:206: ATGAATTCCA TCTTTTATTC CAC 23 INFORMATION FOR SEQ ID NO:207: SEQUENCE CHARACTERISTICS: LENGTH: 27 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori WO 98/24475 PCTIUS97/22104 -285- (ix) FEATURE: NAME/KEY: miscfeature LOCATION 1...27 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:207: AACCATGGTG ATTTTAAGCA TTGAAAG 27 INFORMATION FOR SEQ ID NO:208: SEQUENCE CHARACTERISTICS: LENGTH: 28 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...28 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:208: AAGAATTCCA CTCAAAATTT TTTAACAG 28 INFORMATION FOR SEQ ID NO:209: SEQUENCE CHARACTERISTICS: LENGTH: 25 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...25 WO 98/24475 PCT/US97/22104 -286- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:209: GATCATCCAT ATGTTATCTT CTAAT INFORMATION FOR SEQ ID NO:210: SEQUENCE CHARACTERISTICS: LENGTH: 23 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: miscfeature LOCATION 1...23 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:210: TGAATTCAAC CATTTTAACC CTG 23 INFORMATION FOR SEQ ID NO:211: SEQUENCE CHARACTERISTICS: LENGTH: 27 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: miscfeature LOCATION 1...27 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:211: TATACCATGG TGAAATTTTT TCTTTTA 27 WO 98/24475 PCTIS97/22104 -287- INFORMATION FOR SEQ ID NO:212: SEQUENCE CHARACTERISTICS: LENGTH: 25 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: miscfeature LOCATION 1...25 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:212: AGAATTCAAT TGCGTCTTGT AAAAG INFORMATION FOR SEQ ID NO:213: SEQUENCE CHARACTERISTICS: LENGTH: 24 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...24 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:213: TATACCATGG TGATGGACAA ACTC 24 INFORMATION FOR SEQ ID NO:214: SEQUENCE CHARACTERISTICS: LENGTH: 23 base pairs WO 98/24475 PCTIUS97/22104 -288- TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...23 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:214: ATGAATTCCC ACTTGGGGCG ATA 23 INFORMATION FOR SEQ ID NO:215: SEQUENCE CHARACTERISTICS: LENGTH: 25 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc_feature LOCATION 1...25 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:215: TTATGGATCC AAACCAATTA AAACT INFORMATION FOR SEQ ID NO:216: SEQUENCE CHARACTERISTICS: LENGTH: 23 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular WO 98/24475 PCTI~S97/22104 -289- (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...23 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:216: TATCTCGAGT TATAGAGAAG GGC 23 INFORMATION FOR SEQ ID NO:217: SEQUENCE CHARACTERISTICS: LENGTH: 22 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...22 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:217: TTAACCATGG TGAAAAGCGA TA 22 INFORMATION FOR SEQ ID NO:218: SEQUENCE CHARACTERTSTICS: LENGTH: 24 waje pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO WO 98/24475 PCT/US97/22104 -290- (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...24 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:218: TAGAATTCGC CTCTAAAACT TTAG 24 INFORMATION FOR SEQ ID NO:219: SEQUENCE CHARACTERISTICS: LENGTH: 22 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...22 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:219: TTAACCATGG TGAAAAGCGA TA 22 INFORMATION FOR SEQ ID NO:220: SEQUENCE CHARACTERISTICS: LENGTH: 23 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori WO 98/24475 PCT[US97/22104 -291- (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...23 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:220: TAGAATTCGC ATAACGATCA ATC 23 INFORMATION FOR SEQ ID NO:221: SEQUENCE CHARACTERISTICS: LENGTH: 22 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: miscfeature LOCATION 1...22 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:221: ATATCCATGG TGAGTTTGAT GA 22 INFORMATION FOR SEQ ID NO:222: SEQUENCE CHARACTERISTICS: LENGTH: 25 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: miscfeature LOCATION 1...25 WO 98/24475 PCTfUS97/22104 -292- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:222: ATGAATTCAA TTTTTTATTT TGCCA INFORMATION FOR SEQ ID NO:223: SEQUENCE CHARACTERISTICS: LENGTH: 23 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...23 (xi) SEQUENCE DESCRIPTION: SEQ ID N0:223: AATTCCATGG CTATCCAAAT CCG 23 INFORMATION FOR SEQ ID NO:224: SEQUENCE CHARACTERISTICS: LENGTH: 25 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylor (ix) FEATURE: NAME/KEY: miscfeature LOCATION 1...25 (xi) SEQUENCE DESCRIPTION: SEQ ID N0:224: ATGAATTCGC CAAAATCGTA GTATT WO 98/24475 PCTIUJS9722104 -293- INFORMATION FOR SEQ ID NO:225: SEQUENCE CHARACTERISTICS: LENGTH: 24 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...24 (xi) SEQUENCE DESCRIPTION: SEQ ID N0:225: GATACCATGG AATTTATGAA AAAG 24 INFORMATION FOR SEQ ID NO:226: SEQUENCE CHARACTERISTICS: LENGTH: 25 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KY: misc feature LOC .rJN 1...25 (xi) SEQUENCE DESCRIPTION: SEQ ID N0:226: TGAATTCGAA AAAGTGTAGT TATAC INFORMATION FOR SEQ ID NO:227: SEQUENCE CHARACTERISTICS: WO 98/24475 PCTfUS97/22104 -294- LENGTH: 19 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...19 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:227: CCCTTCATTT TAGAAATCG 19 INFORMATION FOR SEQ ID NO:228: SEQUENCE CHARACTERISTICS: LENGTH: 20 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: miscfeature LOCATION 1...20 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:228: ATTTCAACCA ATTCAATGCG INFORMATION FOR SEQ ID NO:229: SEQUENCE CHARACTERISTICS: LENGTH: 20 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular WO 98/24475 PCTfUS97/22104 -295- (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: miscfeature LOCATION 1...20 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:229: GCCCCTTTTG ATTTGAAGCT INFORMATION FOR SEQ ID NO:230: SEQUENCE CHARACTERISTICS: LENGTH: 22 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc_feature LOCATION 1...22 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:230: TCGCTCCAAG ATACCAAGAA GT 22 INFORMATION FOR SEQ ID NO:231: SEQUENCE CHARACTERISTICS: LENGTH: 22 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO WO 98/24475 PCTIUS97/22104 -296- (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...22 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:231: CTTGAATTAG GGGCAAAGAT CG 22 INFORMATION FOR SEQ ID NO:232: SEQUENCE CHARACTERISTICS: LENGTH: 22 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: miscfeature LOCATION 1...22 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:232: ATGCGTTTTT ACCCAAAGAA GT 22 INFORMATION FOR SEQ ID NO:233: SEQUENCE CHARACTERISTICS: LENGTH: 22 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: WO 98/24475 PCT/US97/22104 -297- ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...22 (xi) SEQUENCE DESCRIPTION: SEQ ID N0:233: ATAACGCCAC TTCCTTATTG GT 22 INFORMATION FOR SEQ ID NO:234: SEQUENCE CHARACTERISTICS: LENGTH: 19 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1....19 (xi) SEQUENCE DESCRIPTION: SEQ ID N0:234: CTTTGGGTAA AAACGCATC 19 INFORMATION FOR SEQ ID NO:235: SEQUENCE CHARACTERISTICS: LENGTH: 20 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) LIF)THETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc_feature WO 98/24475 PCT/US97/22104 -298 LOCATION 1...20 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:235: CGATCTTTGA TCCTAATTCA INFORMATION FOR SEQ ID NO:236: SEQUENCE CHARACTERISTICS: LENGTH: 19 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...19 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:236: ATCAAGTTGC CTATGCTGA 19 INFORMATION FOR SEQ ID NO:237: SEQUENCE CHARACTERISTICS: LENGTH: 22 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc_feature LOCATION 1...22 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:237: WO 98/24475 PCTf(JS97/22104 -299- TTGAACACTT TTGATTATGC GG 22 INFORMATION FOR SEQ ID NO:238: SEQUENCE CHARACTERISTICS: LENGTH: 23 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: miscfeature LOCATION 1...23 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:238: GGATTATGCG ATTGTTTTAC AAG 23 INFORMATION FOR SEQ ID NO:239: SEQUENCE CHARACTERISTICS: LENGTH: 21 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: miscfeature LOCATION 1...21 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:239: GTCTTTAGCA AAAATGGCGT C 21 INFORMATION FOR SEQ ID NO:240: WO 98/24475 PCT/US97/22104 -300- SEQUENCE CHARACTERISTICS: LENGTH: 21 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: miscfeature LOCATION 1...21 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:240: AATGAGCGTA AGAGAGCCTT C 21 INFORMATION FOR SEQ ID NO:241: SEQUENCE CHARACTERISTICS: LENGTH: 18 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: miscfeature LOCATION 1...18 (xi) SEQUENCE DESCRIPTION SEQ ID NO:241: CTTATGGGGG TATTGTCA 18 INFORMATION FOR SEQ ID NO:242: SEQUENCE CHARACTERISTICS: LENGTH: 18 base pairs TYPE: nucleic acid STRANDEDNESS: double WO 98/24475 PCTfUS97/22104 -301- TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...18 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:242: AGCATGTGGG TATCCAGC 18 INFORMATION FOR SEQ ID NO:243: SEQUENCE CHARACTERISTICS: LENGTH: 19 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...19 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:243: AGGTTGTTGC CTAAAGACT 19 7NFORMATION FOR SEQ ID NO:244: SEQUENCE CHARACTERISTICS: LENGTH: 18 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) WO 98/24475 PCT/US97/22104 -302- (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc_feature LOCATION 1...18 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:244: CTGCCTCCAC CTTTGATC 18 INFORMATION FOR SEQ ID NO:245: SEQUENCE CHARACTERISTICS: LENGTH: 19 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc_feature LOCATION 1...19 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:245: ACCAATATCA ATTGGCACT 19 INFORMATION FOR SEQ ID NO:246: SEQUENCE CHARACTERISTICS: LENGTH: 18 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO WO 98/24475 PCTIS97/22104 -303- (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...18 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:246: ACTTGGAAAA GCTCTGCA 18 INFORMATION FOR SEQ ID NO:247: SEQUENCE CHARACTERISTICS: LENGTH: 19 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...19 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:247: CTTGCTTGTC ATATCTAGC 19 INFORMATION FOR SEQ ID NO:248: SEQUENCE CHARACTERISTICS: LENGTH: 18 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: WO 98/24475 PCT/US97/22104 -304- NAME/KEY: miscfeature LOCATION 1...18 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:248: GTTGAAGTGT TGGTGCTA 18 INFORMATION FOR SEQ ID NO:249: SEQUENCE CHARACTERISTICS: LENGTH: 22 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...22 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:249: CAAGCAAGTG GTTTGGTTTT AG 22 INFORMATION FOR SEQ ID NO:250: SEQUENCE CHARACTERISTICS: LENGTH: 22 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: ',O (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...22 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:250: WO 98/24475 PCTIUS97/22104 S-305- TGGAAAGAGC AAATCATTGA AG 22 INFORMATION FOR SEQ ID NO:251: SEQUENCE CHARACTERISTICS: LENGTH: 21 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: miscfeature LOCATION 1...21 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:251: GCCCATAATC AAAAAGCCCA T 21 INFORMATION FOR SEQ ID NO:252: SEQUENCE CHARACTERISTICS: LENGTH: 24 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc_feature LOCATION 1...24 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:252: CTAAAACCAA ACCACTTGCT TGTC 24 INFORMATION FOR SEQ ID NO:253: WO 98/24475 PCTfUS97/22104 -306- SEQUENCE CHARACTERISTICS: LENGTH: 16 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...16 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:253: GTAAAACGAC GGCCAG 16 INFORMATION FOR SEQ ID NO:254: SEQUENCE CHARACTERISTICS: LENGTH: 17 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: miscfeature LOCATION 1...17 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:254: CAGGAAACAG CTATGAC 17 INFORMATION FOR SEQ ID NO:255: SEQUENCE CHARACTERISTICS: LENGTH: 21 base pairs TYPE: nucleic acid WO 98/24475 PCTIUJS97/22104 -307- STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: miscfeature LOCATION 1...21 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:255: ATCTTACCTA TCACCTCAAA T 21 INFORMATION FOR SEQ ID NO:256: SEQUENCE CHARACTERISTICS: LENGTH: 21 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: miscfeature LOCATION 1...21 (xi) SEQUENCE DESCRIPTION: SEQ ID N0:256: AGACAGCAAC ATCTTTGTGA A 21 INFORMATION FOR SEQ ID NO:257: SEQUENCE CHARACTERISTICS: LENGTH: 50 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) WO 98/24475 PCTIUS97/22104 -308- (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...50 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:257: CGCGGATCCA TATGGCTGAA AAAACGCCTT TTTTTAAAAC TAAAAACCAC INFORMATION FOR SEQ ID NO:258: SEQUENCE CHARACTERISTICS: LENGTH: 34 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: miscfeature LOCATION 1...34 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:258: CCGGAATTCA TCAGTATTCA ATGGGAATAA AGCC 34 INFORMATION FOR SEQ ID NO:259: SEQUENCE CHARACTERISTICS: LENGTH: 50 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO WO 98/24475 PCT/US97/22104 -309- (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: miscfeature LOCATION 1...50 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:259: CGCGGATCCA TATGAAAGAA GAAGAAAAAG AAGAAAAAAA GACAGAAAGG INFORMATION FOR SEQ ID NO:260: SEQUENCE CHARACTERISTICS: LENGTH: 37 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...37 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:260: CCGGAATTCG CTTAAAAGAA AATAGTCCCC CAAACGC 37 INFORMATION FOR SEQ ID NO:261: SEQUENCE CHARACTERISTICS: LENGTH: 43 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori WO 98/24475 PCTIUS97/22104 -310- (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...43 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:261: CGCGGATCCA TATGAAAGAG GTCATTCCCA CCCCTTCAAC CCC 43 INFORMATION FOR SEQ ID NO:262: SEQUENCE CHARACTERISTICS: LENGTH: 36 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: miscfeature LOCATION 1...36 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:262: CCGGAATTCA TATAAATATC ATATAGGCAG AAAAAC 36 INFORMATION FOR SEQ ID NO:263: SEQUENCE CHARACTERISTICS: LENGTH: 37 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...37 WO 98/24475 PCT/US97/22104 -311- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:263: CGCGGATCCA TATGGAGGCA GAGCTTGATG AAAAATC 37 INFORMATION FOR SEQ ID NO:264: SEQUENCE CHARACTERISTICS: LENGTH: 36 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...36 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:264: CCGGAATTCG ATTGATTTTG TCAAATCTAA AATCCC 36 INFORMATION FOR SEQ ID NO:265: SEQUENCE CHARACTERISTICS: LENGTH: 25 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicohacter pylori (ix) FEATURE: NAME/KEY: misc_feature LOCATION 1...25 (xi) SEQUENCE DESCRIPTION: SEQ ID N0:265: TATTATACAT ATGGAAGAAG ATGGG WO 98/24475 PCTfUS97/22104 -312- INFORMATION FOR SEQ ID NO:266: SEQUENCE CHARACTERISTICS: LENGTH: 23 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...23 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:266: TAATCTCGAG TTTAGAAGGC GTA 23 INFORMATION FOR SEQ ID NO:267: SEQUENCE CHARACTERISTICS: LENGTH: 25 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: miscfeature LOCATION 1...25 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:267: TTATATTCAT ATGGAAGACG ATGGC INFORMATION FOR SEQ ID NO:268: SEQUENCE CHARACTERISTICS: LENGTH: 24 base pairs WO 98/24475 PCTIUS97/22104 -313- TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...24 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:268: AATTCTCGAG CCTCTTTATA AGCC 24 INFORMATION FOR SEQ ID NO:269: SEQUENCE CHARACTERISTICS: LENGTH: 46 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: miscfeature LOCATION 1...46 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:269: CGCGGATCCA TATGGTAGAA GCCTTTCAAA AACACCAAAA AGACGG 46 INFORMATION FOR SEQ ID NO:270: SEQUENCE CHARACTERISTICS: LENGTH: 32 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular WO 98/24475 PCTIUS97/22104 -314- (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: miscfeature LOCATION 1...32 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:270: CCGGAATTCG GAGCCAATAG GGAGCTAAAG CC 32 INFORMATION FOR SEQ ID NO:271: SEQUENCE CHARACTERISTICS: LENGTH: 31 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...31 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:271: CGGGATCCGA AGGTGATGGT GTTTATATAG G 31 INFORMATION FOR SEQ ID NO:272: SEQUENCE CHARACTERISTICS: LENGTH: 32 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO WO 98/24475 PCTfUS97/22104 -315- (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: miscfeature LOCATION 1...32 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:272: CGCATATGGA AGGTGATGGT GTTTATATAG GG 32 INFORMATION FOR SEQ ID NO:273: SEQUENCE CHARACTERISTICS: LENGTH: 37 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: miscfeature LOCATION 1...37 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:273: GCGAATTCTC ACTCTTTCCA ATAGTTTGCT GCAGAGC 37 INFORMATION FOR SEQ ID NO:274: SEQUENCE CHARACTERISTICS: LENGTH: 37 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori WO 98/24475 PCT/US97/22104 -316- (ix) FEATURE: NAME/KEY: misc feature LOCATION 1...37 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:274: CCGGAATTCT TAATCCCGTT TCAAATGGTA ATAAAGG 37 INFORMATION FOR SEQ ID NO:275: SEQUENCE CHARACTERISTICS: LENGTH: 36 base pairs TYPE: nucleic acid STRANDEDNESS: double TOPOLOGY: circular (ii) MOLECULE TYPE: DNA (genomic) (iii) HYPOTHETICAL: NO (iv) ANTI-SENSE: NO (vi) ORIGINAL SOURCE: ORGANISM: Helicobacter pylori (ix) FEATURE: NAME/KEY: miscfeature LOCATION 1...36 (xi) SEQUENCE DESCRIPTION: SEQ ID N0:275: GCGAATTCCC TTTTATTTAA AAAGTGTAGT TATACC 36

Claims

2. The isolated nucleic acid of claim 1, comprising a nucleotide sequence selected 0o from the group consisting of SEQ ID NO: 5, 11, 14, 26, 28, 36,42, 51, 52 and 79, or a complement thereof.
3. An isolated nucleic acid which encodes an H. pylori polypeptide, comprising a nucleotide sequence at least 60% homologous to a nucleotide sequence selected from the group consisting of SEQ ID NO: 5, 11, 14, 26, 28, 36, 42, 51, 52 and 79, or a complement thereof.
4. An isolated nucleic acid molecule encoding an H. pylori polypeptide, comprising a nucleotide sequence which hybridizes under stringent hybridization conditions to a nucleic acid molecule comprising the nucleotide sequence selected from the group **..:consisting of SEQ ID NO: 5,11, 14,26, 28, 36, 42, 51, 52 and 79, or a complement thereof.
5. An isolated nucleic acid comprising a nucleotide sequence of at least 8 25 nucleotides in length, wherein the sequence hybridizes under stringent hybridization conditions to a nucleic acid having a nucleotide sequence selected from the group consisting of SEQ ID NO: 5, 11, 14, 26, 28, 36, 42, 51, 52 and 79, or a complement thereof. 3 6. An isolated nucleic acid comprising a nucleotide sequence encoding an H. pylori cell envelope polypeptide or a fragment thereof, said nucleotide sequence being at least 60% homologous to a nucleotide sequence selected from the group consisting of SEQ ID NO: 14, SEQ ID NO: 28, SEQ ID NO: 51, SEQ ID NO: 79, SEQ ID NO: 5, SEQ ID NO: 11, SEQ ID NO: 26, SEQ ID NO: 36, SEQ ID NO: 42 and SEQ ID NO: 52, or a 3s complement thereof. 318
7. The isolated nucleic acid of claim 6, wherein said H. pylori cell envelope polypeptide or a fragment thereof is an H. pylori outer membrane polypeptide or a fragment'thereof encoded by a nucleotide sequence at least 60% homologous to a nucleotide sequence selected from the group consisting of SEQ ID NO: 14, SEQ ID NO: s 28, SEQ ID NO: 51, SEQ ID NO: 79, SEQ ID NO: 5, SEQ ID NO: 11, SEQ ID NO: 26, SEQ ID NO: 36, SEQ ID NO: 42 and SEQ ID NO: 52, or a complement thereof.
8. The isolated nucleic acid of claim 7, wherein said H. pylori outer membrane polypeptide or a fragment thereof is an H. pylori polypeptide having a terminal to phenylalanine residue or a fragment thereof encoded by a nucleotide sequence at least homologous to a nucleotide sequence selected from the group consisting of SEQ ID NO: 11, SEQ ID NO: 14, SEQ ID NO: 26, SEQ ID NO: 28, SEQ ID NO: 36, SEQ ID NO: 42, SEQ ID NO: 51, SEQ ID NO: 52 and SEQ ID NO: 79, or a complement thereof.
9. The isolated nucleic acid of claim 8, wherein said H. pylori outer membrane polypeptide or a fragment thereof is an H. pylori polypeptide having a terminal phenylalanine residue and a C-terminal tyrosine cluster or a fragment thereof encoded by a nucleotide sequence at least 60% homologous to a nucleotide sequence selected from the group consisting of SEQ ID NO: 11, SEQ ID NO: 26, SEQ ID NO: 36, SEQ ID NO: 42, and SEQ ID NO: 52, or a complement thereof.
10. An isolated nucleic acid comprising a nucleotide sequence encoding an H. pylori cell envelope polypeptide or a fragment thereof, wherein said polypeptide comprises an amino acid sequence that is at least 60% homologous to an amino acid sequence selected from the group consisting ofSEQ NO 1, SEQ ID NO: 12, SEQ ID NO: 125, ID NO: 148, SEQ ID NO: 176, SEQ ID NO: 177, SEQ ID NO: 102, SEQ ID NO: 108, SEQ ID NO: 123, SEQ ID NO: 133, SEQ ID NO: 139 and SEQ ID NO: 149.
11. The isolated nucleic acid of claim 10, wherein said H. pylori cell envelope 3o polypeptide or a fragment thereof is an H. pylori outer membrane polypeptide or a fragment thereof comprising an amino acid sequence that is at least 60% homologous to an amino acid sequence selected from the group consisting of SEQ ID NO: 111, SEQ ID NO: 121, SEQ ID NO: 125, SEQ ID NO: 148, SEQ ID NO: 176, SEQ ID NO: 177, SEQ ID t* NO: 102, SEQ ID NO: 108, SEQ ID NO: 123, SEQ ID NO: 133, SEQ ID NO: 139 and SEQ ID NO: 149.
12. The isolated nucleic acid of claim 11, wherein said H. pylori outer membrane polypeptide or a fragment thereof is an H. pylori polypeptide having a terminal phenylalanine residue or a fragment thereof comprising an amino acid sequence that is at least 60% homologous to an amino acid sequence selected from the group consisting of s SEQ ID NO: 108, SEQ ID NO: 111, SEQ ID NO: 121, SEQ ID NO: 123, SEQ ID NO: 125, SEQ ID NO: 133, SEQ ID NO: 139, SEQ ID NO: 148, SEQ ID NO: 149, SEQ ID NO: 176 and SEQ ID NO: 177.
13. The isolated nucleic acid of claim 12, wherein said H. pylori outer membrane polypeptide or a fragment thereof is an H. pylori polypeptide having a terminal phenylalanine residue and a C-terminal tyrosine cluster or a fragment thereof comprising an amino acid sequence that is at least 60% homologous to an amino acid sequence selected from the group consisting of SEQ ID NO: 108, SEQ ID NO: 123, SEQ ID NO: 133, SEQ ID NO: 139, and SEQ ID NO: 149.
14. The isolated nucleic acid of any one of claims 3,6, 7, 8 and 9, wherein the nucleotide sequence comprised by the nucleic acid is at least 70%, 80%, 90%, 95%, 98%, or 99% homologous to the selected nucleotide sequence, or identical to the selected nucleotide sequence.
15. The isolated nucleic acid of any one of claims 1, 10, 11 and 12, wherein said H. pylori polypeptide is at least 70%, 80%, 90%, 95%, 98% or 99% homologous to the selected amino acid sequence, or identical to the selected animo acid sequence.
16. A probe comprising a nucleotide sequence consisting of at least 8 nucleotides of a nucleotide sequence selected from the group consisting of SEQ ID NO: 5, 11, 14, 26, 28, 36, 42, 51, 52 and 79, or a complement thereof.
17. A recombinant expression vector comprising the nucleic acid of any one of 30 claims I to 14, wherein the nucleic acid includes a transcription regulatory element operably linked to the nucleotide sequence comprised by the nucleic acid.
18. A cell comprising a recombinant expression vector of claim 17.
19. A method for producing an H. pylori polypeptide comprising culturing a cell of claim 18 under conditions that permit expression of the polypeptide. 320 The method of claim 19, further comprising purifying the polypeptide from the cell. s 21. A method for detecting the presence of a Helicobacter nucleic acid in a sample comprising: (a)contacting a sample with a nucleic acid of any one of claims 1 to 16 so that a hybrid can form between the probe and a Helicobacter nucleic acid in the sample; and (b)detecting the hybrid formed in step wherein detection of a hybrid indicates the presence of a Helicobacter nucleic acid in the sample.
22. An isolated H. pylori polypeptide comprising an amino acid sequence at least homologous to an H. pylori amino acid sequence selected from the group consisting of SEQ ID NO: 102, 108, 111,121,123, 125, 133, 139, 148, 149, 176 and 177.
23. An isolated H. pylori polypeptide which is encoded by a nucleic acid comprising a nucleotide sequence at least 60% homologous to a nucleotide sequence selected from the group consisting of SEQ ID'NO: 5, 11, 14, 26, 28, 36, 42, 51, 52 and 79.
24- An isolated H. pylori polypeptide comprising an amino acid sequence at least 60% homologous to an H. pylori amino acid sequence selected from the group consisting ofSEQ ID NO: 102, 108, 111, 121,123, 125, 133, 139, 148, 149, 176 and 177.
25. An isolated H. pylori polypeptide which is encoded by a nucleic acid comprising 25 a nucleotide sequence at least 60% homologous to a nucleotide sequence selected from the group consisting of SEQ ID NO: 5, 11, 14, 26, 28, 36, 42, 51, 52 and 79. An isolated H. pylori polypeptide which is encoded by a nucleic acid which hybridizes under stringent hybridization conditions to a nucleic acid selected from the 30 group consisting of SEQ ID NO: 5, 11, 14, 26, 28, 36, 42, 51, 52 and 79, or a complement thereof. i 27. An isolated H. pylori cell envelope polypeptide or a fragment thereof, wherein said polypeptide comprises an amino acid sequence that is at least 60% homologous to an amino acid sequence selected from the group consisting of SEQ ID NO: 111, SEQ ID NO: 21, SEQ ID NO: 125, SEQ ID NO: 148, SEQ ID NO: 176, SEQ ID NO: 177, SEQ ID 321 NO: 102, SEQ ID NO: 108, SEQ ID NO: 123, SEQ ID NO: 133, SEQ ID NO: 139 and SEQ ID NO: 149.
28. The isolated polypeptide of claim 27, wherein said H pylori cell envelope polypeptide or a fragment thereof is an H. pylori outer membrane polypeptide or a fragment thereof comprising an amino acid sequence that is at least 60% homologous to an amino acid sequence selected from the group consisting of SEQ ID NO: 111, SEQ ID NO: 121, SEQ ID NO: 125, SEQ ID NO: 148, SEQ ID NO: 176, SEQ ID NO: 177, SEQ ID NO: 102, SEQ ID NO: 108, SEQ ID NO: 123, SEQ ID NO: 133, SEQ ID NO: 139 and SEQ ID NO: 149.
29. The isolated polypeptide of claim 28, wherein said H. pylori outer membrane polypeptide or a fragment thereof is an H. pylori polypeptide having a terminal phenylalanine residue or a fragment thereof comprising an amino acid sequence that is at is least 60% homologous to an amino acid sequence selected from the group consisting of SEQ ID NO: 108, SEQ ID NO: 111, SEQ ID NO: 121, SEQ ID NO: 123, SEQ ID NO: 125, SEQ ID NO: 133, SEQ ID NO: 139, SEQ ID NO: 148, SEQ ID NO: 149, SEQ ID NO: 176 and SEQ ID NO: 177.
30. The isolated polypeptide of claim 29, wherein said H. pylori outer membrane polypeptide or a fragment thereof is an H. pylori polypeptide having a terminal phenylalanine residue and a C-terminal tyrosine cluster or a fragment thereof comprising i. an amino acid sequence that is at least 60% homologous to an amino acid sequence selected from the group consisting of SEQ ID NO: 108, SEQ ID NO: 123, SEQ ID NO: S !33, SEQ iD NO: 39, and S.EQ TD NO 149.
31. An isolated H. pylori cell envelope polypeptide or a fragment thereof, wherein said polypeptide is encoded by a nucleic acid comprising a nucleotide sequence that is at least 60% homologous to a nucleotide sequence selected from the group consisting of SEQ S 30 ID NO: 14, SEQ ID: 28, SEQ ID NO: 51, SEQ ID NO: 79, SEQ ID NO: 5, SEQ ID NO: 11, SEQ ID NO: 26, SEQ ID NO: 36, SEQ ID NO: 42 and SEQ ID NO: 52.
32. The isolated polypeptide of claim 31, wherein said H. pylori cell envelope polypeptide or a fragment thereof is an H. pylorl outer membrane polypeptide or a fragment thereof encoded by a nucleic acid comprising a nucleotide sequence that is at least 60% homologous to a nucleotide sequence selected from the group consisting of SEQ 322 ID NO: 14, SEQ ID NO: 28, SEQ ID NO: 51, SEQ ID NO: 79, SEQ ID NO: 5, SEQ ID NO: 11, SEQ ID NO: 26, SEQ ID NO: 36, SEQ ID NO: 42 and SEQ ID NO: 52.
33. The isolated polypeptide of claim 32, wherein said H. pylori outer membrane s polypeptide or a fragment thereof is an H. pylori polypeptide having a terminal phenylalanine residue or a fragment thereof encoded by a nucleic acid comprising a nucleotide sequence that is at least 60% homologous to a nucleotide sequence selected from the group consisting-of SEQ ID NO: 11, SEQ ID NO: 14, SEQ ID NO: 26, SEQ ID NO: 28, SEQ ID NO: 36, SEQ ID NO: 42, SEQ ID NO: 51, SEQ ID NO: 52 and SEQ ID NO: 79.
34. The isolate. polypeptide of claim 33, wherein said H. pylori outer membrane polypeptide or a fragment thereof is an H. pylori polypeptide having a terminal phenylalanine residue and a C-terminal tyrosine cluster or a fragment thereof encoded by a nucleic acid comprising a nucleotide sequence that is at least 60% homologous to a nucleotide sequence selected from the group consisting of SEQ ID NO: 11, SEQ ID NO: 26, SEQ ID NO: 36, SEQ ID NO: 42, and SEQ ID NO: 52. The isolated polypeptide of any one of claims 22, 24 and 27 to 30, wherein said amino acid sequence comprised by the isolated polypeptide is at least 70%, 80%, 98% or 99% homologous to the selected amino acid sequence, or identical to the selected amino acid sequence. i 0
36. The isolated polypeptide of any one of claims 23, 25 and 31 to 34, wherein the 2s nucleotide sequence comprised by the nucleic acid is at least 80%, 80%, 8% or 99% homologous to the selected nucleotide sequence, or identical to the selected nucleotide sequence.
37. A fusion protein comprising an H. pylori polypeptide which comprises an amino 30 acid sequence that is at least 60% homologous to an amino acid sequence selected from the group consisting of SEQ ID NO: 102, 108, 111, 121,123, 125, 133, 139, 148, 149, 176 and 177 operatively linked to a non-H. pylori polypeptide.
38. A vaccine formulation for prophylactic or therapeutic treatment of an H pylori infection comprising an effective amount of at least one isolated nucleic acid of any one of claims 1 to 323
39. A vaccine formulation for prophylactic or therapeutic treatment of an H. pylori infection comprising an effective amount of at least one isolated nucleic acid encoding an H. pylori outer membrane polypeptide or a fragment thereof, said nucleic acid comprising a s nucleotide sequence that is at least 60% homologous to a nucleotide sequence selected from the group consisting of SEQ ID NO: 28, SEQ ID NO: 11, SEQ ID NO: 52, SEQ ID NO: 42 and SEQ ID NO: 79. The vaccine formulation of claim 39, wherein said nucleic acid comprises a o0 nucleotide sequence that is at least 60% homologous to SEQ ID NO: 52.
41. The vaccine formulation of claim 39 or 40, wherein the nucleotide sequence comprised by the nucleic acid is at least 70%, 80%, 90%, 95%, 98%, or 99% homologous to the selected nucleotide sequence, or identical to the selected nucleotide sequence.
42. The vaccine formulation any one of claims 38 to 41, including genetically engineered attenuated live viruses or bacteria, or recombinant virus-like particles
43. A vaccine formulation for prophylactic or therapeutic treatment of an H. pylori infection comprising an effective amount of at least one H. pylor polypeptide or a fragment thereof of any one of claims 22 to 36. *oo a
44. A vaccine formulation for prophylactic or therapeutic treatment of an H pylori infection comprising an effective amount of at least one H. pylori outer membrane 2 polypeptide or a fragment thereof, said polypeptide comprising an amino acid sequence that is at least 60% homologous to an amino acid sequence selected from the group consisting of SEQ ID NO: 125, SEQ ID NO: 121, SEQ ID NO: 108, SEQ ID NO: 149, SEQ ID NO: 139 and SEQ ID NO: 176.
45. The vaccine formulation of claim 44, wherein said polypeptide comprises an amino acid sequence that is at least 60% homologous to SEQ ID NO: 149.
46. The vaccine formulation of claim 44 or 45, including a substance selected from cholera toxin, a non-toxic derivative of cholera toxin, procholeragenoid, a fungal polysaccharide, muramyl dipeptide, a muramyl dipeptide derivative, a phorbol ester, E. coli labile toxin, a non-H pylori bacterial lysate, a block polymer, a saponin, biodegradable 324 microcapsules, ISCOMs, cochleates, liposomes, genetically engineered attenuated live viruses or bacteria, and recombinant virus-like particles.
47. A vaccine formulation of any one of claims 38 to 46, further comprising a s pharmaceutically acceptable carrier.
48. A vaccine formulation of claim 47, wherein the pharmaceutically acceptable carrier comprises an adjuvant.
49. A vaccine formulation of claim 47 or 48, wherein the pharmaceutically acceptable carrier comprises a delivery system. A vaccine formulation of claim 49, wherein the delivery system comprises a live vector. s1
51. A vaccine formulation of claim 50, wherein the live vector is a bacterium or a virus.
52. A method of treating or reducing a risk of H. pylori infection in a subject 20 comprising administering to a subject a vaccine formulation of any one of claims 38 to 51, such that treatment or reduction of risk ofH. pylori infection occurs.
53. A method of producing a vaccine formulation comprising: combining at least one isolated H. pylori polypeptide according to claim 24 with a pharmaceutically acceptable 2 L carrier ,I er y ,fonrm a vacn oVSrmlai.. 54, A method of producing a vaccine formulation comprising: culturing a cell under condition that permit expression of an H. pylori polypeptide according to claim 24; 30 (b)isolating said H. pylori polypeptide or a fragent thereof from said cell; and (c)combining at least one said isolated H. pylori polypeptide or a fragment thereof with a pharmaceutically acceptable carrier to thereby form a vaccine formulation.
55. A chimeric H. pylori polypeptide comprising the amino acid sequences of at least two H. pylori polypeptides or fragments thereof, wherein each of said amino acid sequences is encoded by a nucleotide sequence that is identical to a first nucleotide sequence as defined in claim 3.
56. A chimeric H. pylori polypeptide comprising the amino acid sequence of at least s two H. pylorl polypeptides or fragments thereof, wherein each of said amino acid sequences is identical to a first amino acid sequence as defined in claim 24.
57. Use of the isolated nucleic acid according to any one of claims 1 to 15, in the manufacture of a vaccine composition, for treating a subject for H. pylori infection.
58. Use of the purified polypeptide of any one of claims 22 to 36 in the manufacture of a vaccine composition, for treating a subject for H. pylori infection.
59. The use according to claim 57 or 58, wherein the treatment is a prophylactic treatment, The use according to claim 57 or 58, wherein the treatment is a therapeutic treatment. 20 61. A drug screening assay comprising the step of contacting a test compound with a purified polypeptide comprising an amino acid sequence that is at least 60% homologous to an amino acid sequence selected from SEQ ID NO: 102, 108, 111, 121, 123, 125, 133, 139, 148, 149, 176 and 177. 25 62. The assay of claim 61, comprising determining if the compound binds to said amino acid sequence of the purified polypeptide.
63. The assay of claim 61 or 62, comprising determining if the test compound alters the binding affinity of said amino acid sequence of the purified polypeptide for a ligand 3o thereof.
64. The assay of claim 63, wherein the ability of the test compound to inhibit the binding ability of said amino acid sequenced to the ligand is determined. 326 The assay of claim 61 or 62wherein the polypeptide has enzymatic activity, and the assay comprises detecting if the test compound changes the enzymatic activity.
66. The assay of claim 65, wherein the enzymatic activity produces a detectable reaction product with distinctive absorption, fluorescence or chemi-luminescence properties.
67. The assay of any one of claims 61 to 66, wherein the assay is a cell-free assay. to 68. The assay of any one of claims 61 to 67, wherein the amino acid sequence comprised by the purified polypeptide is at least 70%, 80%, 90%, 95%, 98% or 99% homologous to the selected amino acid sequence, or identical to the selected amino acid sequence.
69. A drug screening assay comprising the step of contacting a test compound with San isolated nucleic acid comprising a nucleotide sequence that is at least 60% homologous to a nucleotide sequence selected from SEQ ID NO: 5, 11, 14, 26, 28, 36, 42, 51, 52 and 79, or a complement thereof 0 70. The assay of claim 69, comprising determining if the compound binds to, or interacts with, said nucleotide sequence of the nucleic acid.
71. The assay of claim 69, wherein the assay is an in vitro assay. 9 25 72. The assay of any one of claims 69 to 71, wherein the nucleotide sequence comprised by the nucleic acid is at least 70%, 80%, 90%, 95%, 98% or 99% homologous to the selected nucleotide sequence, or identical to the selected nucleotide sequence. DATED this 27 day of August 2001 ASTRA AKTIEBOLAG, By i-:ts Patent Attorneys, e F WELLn CO., 7 .(Brtfe Wellington)