CZ148399A3 - Sequence of nucleic acids and amino acids connected with Helicobacter pylori and vaccine preparations - Google Patents

Abstract

They are described recombinantly or substantially purified Hpylori polypeptide preparations are also described acid encoding polypeptides. Polypeptides Hpylorijsou useful for the production of diagnostic and vaccine resources.

Description

The present invention relates to nucleic acid and amino acid sequences relating to Helicobacter pylori and vaccine compositions comprising them. ’

BACKGROUND OF THE INVENTION

Helicobacter pylori is a gram-negative microaerophilic, S-shaped microaerophilic bacterium that has been discovered and cultured from biopsy samples from the stomach. (Warren, J.R. et al., And B. Marshall (1983) Lancet 1: 1273-1275; and Marshall et al. (1984) Microbios Lett.

25: 83-88). H. pylori has been strongly bound to chronic gastritis and duodenal ulcer (Rathbone et al., (1986) Gut 27: 635-641).

In addition, evidence is accumulating for the etiological role of H. pylori in nonulcerous dyspepsia, gastric ulcers and gastric adenocarcinoma (Blaser M.J. (1993) Trends Microbiol. 1: 255-260). Infection 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 gastric mucosa and develops an infection that persists for decades. The prevalence of H. pylori infection is worldwide. In developed countries, the infection rate is more than 50% for the adult population, while developing countries have an infection rate of 90% for adults over 20 years of age. (Hopkins R. J. and J. G. Morris (1994) Am. J. Med. 97: 265-277).

Bacterial factors necessary for colonization of the stomach environment and for virulence of this pathogen are little known. Examples of putative virulence factors include, for example: urease, an enzyme that can play a role in neutralizing the acidic pH in the stomach, »

(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); bacterial flagellin proteins responsible for motility through. mucosal layer (Hazeli et al., (1986) J. Inf. Dis. 153: 658)

663; Leying et al. (1992) Mol. Microbiol. 6: 2863-2874; and Haas et al .; (1993) Mol. Microbiol. 8: 753-760); VacA, 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 (Bořen et al., (1993) Science 262: 1892 - 1895;

Evans et al., (1993) J. Bacteriol. 175: 674-683; and Falk et al.,:, 11993) Proc. Nati. Acad. Sci. USA 90: 2035-203).

Many therapeutic agents are currently available that eradicate H. pylori in.vitro infection (Huesca et al. (1993) Zbl. Bakt. 280: 244-252; Hopkins, RJ and JG Morris, supra). of these treatments is suboptimal in vivo due to bacterial resistance, altered distribution, cure non-patient compliance or poor drug availability (Hopkins, RJ and JG Morris, supra). Antibiotic therapy in combination with bismuth is part of the standard regimen used to treat H. pylori infection (Malfertheiner, P. and J.E. Dominguez-Munoz (1993) Clinical Therapeutics 15 Supp. B: 37-48). It has recently been shown that the combination of a proton pump inhibitor and one antibiotic alleviates the duodenal ulcer (Malfertheiner, P. and J.E. Dominguez-Munoz, supra). However, antibiotic treatment methods may involve the risk of developing bacterial strains that are resistant to these agents (Hopkins, R.J. and J.G. Morris, supra). These limitations indicate the need for a new effective method for treating H. pylori infection in vivo. In particular, it is desirable to develop new vaccines that may prevent infection by these bacteria.

SUMMARY OF THE INVENTION

The present invention relates to novel genes, for example genes encoding peptides such as bacterial surface proteins, from Helicobacter pylori (H. pylori) and other related genes, their products and their uses. The nucleic acids and peptides of the present invention are useful as diagnostic and therapeutic agents 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 more particularly, the invention relates to nucleic acid compositions corresponding to the entire coding sequence for H. pylori proteins, including surface and secreted proteins. or parts thereof, nucleic acids that can bind to mRNAs of H. pylori proteins and thus block translation of proteins and methods for producing H. pylori proteins or parts thereof using peptide synthesis and recombinant DNA techniques. The invention also relates to antibodies and nucleic acids that are useful as probes for detecting H. pylori infection. Furthermore, the invention relates to vaccines and methods for protecting against H. pylori infection or treating H. pylori infection.

Description of the figures in the attached drawings

Giant. 1 is a bar graph depicting the antibody titer in the serum of mice after immunization with specific H. pylori antigens.

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

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

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

Figure 5 shows the amino acid alignment in part of the sequence of the five H. pylori proteins (shown in the one letter amino acid code; from N-terminus to C-terminus, left to right).

Giant. 6 shows the amino acid alignment in the portion of the sequence of four H. pylori proteins (shown in the one letter amino acid code; from N-terminus to C-terminus, left to right).

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

Giant. 8 shows the alignment of amino acids in a portion of the sequence of two H. pylori proteins (shown in the one letter amino acid code; from N-terminus to C-terminus, left to right).

In one aspect, the invention comprises a recombinant or substantially purified preparation of an H. pylori polypeptide of SEQ ID NO: 74. The invention also includes a significantly purified nucleic acid encoding an H. pylori polypeptide of SEQ ID NO: 74, which is set forth in SEQ ID NO: 1. Polypeptide Sequence H. pylori of the present invention are listed in the Sequence Listing and nucleic acids encoding H. pylori polypeptides of the present invention are listed in the Sequence Listing.

In another aspect, the invention comprises a significantly purified nucleic acid encoding an H. pylori polypeptide having the amino acid sequence of SEQ ID NO: 75, such as a nucleic acid comprising the nucleotide sequence set forth in SEQ ID NO: 2.

In another aspect, the invention comprises a significantly purified nucleic acid encoding an H. pylori polypeptide having

an amino acid sequence of SEQ ID NO: 76, such as a nucleic acid comprising the nucleotide sequence set forth in SEQ ID NO: 3.

In another aspect, the invention comprises a significantly purified nucleic acid encoding a H. pylori polypeptide having the amino acid sequence of SEQ ID NO: 77, such as a nucleic acid comprising the nucleotide sequence set forth in SEQ ID NO: 4.

In another aspect, the invention includes a significantly purified nucleic acid encoding an H. pylori polypeptide having the amino acid sequence of SEQ ID NO: 78, such as a nucleic acid comprising the nucleotide sequence set forth in SEQ ID NO: 5.

In another aspect, the invention comprises a significantly purified nucleic acid encoding an H. pylori polypeptide having the amino acid sequence of SEQ ID NO: 79, such as a nucleic acid comprising the nucleotide sequence set forth in SEQ ID NO: 6.

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In another aspect, the invention comprises a significantly purified nucleic acid encoding an H. pylori polypeptide having the amino acid sequence of SEQ ID NO: 80, such as a nucleic acid comprising the nucleotide sequence set forth in SEQ ID NO: 7.

In another aspect, the invention comprises a significantly purified nucleic acid encoding an H. pylori polypeptide having the amino acid sequence of SEQ ID NO: 81, such as a nucleic acid comprising the nucleotide sequence set forth in SEQ ID NO: 8.

In another aspect, the invention comprises a significantly purified nucleic acid encoding an H. pylori polypeptide having the amino acid sequence of SEQ ID NO: 82, such as a nucleic acid comprising the nucleotide sequence set forth in SEQ ID NO: 9.

In another aspect, the invention comprises a significantly purified nucleic acid encoding an H. pylori polypeptide having the amino acid sequence of SEQ ID NO: 83, such as a nucleic acid comprising the nucleotide sequence set forth in SEQ ID NO: 10.

In another aspect, the invention comprises a significantly purified nucleic acid encoding an H. pylori polypeptide having the amino acid sequence of SEQ ID NO: 84, such as a nucleic acid comprising the nucleotide sequence set forth in SEQ ID NO: 11.

In another aspect, the invention comprises a significantly purified nucleic acid encoding an H. pylori polypeptide having the amino acid sequence of SEQ ID NO: 85, such as a nucleic acid comprising the nucleotide sequence set forth in SEQ ID NO: 12.

In another aspect, the invention comprises a significantly purified nucleic acid encoding an H. pylori polypeptide having the amino acid sequence of SEQ ID NO: 86, such as a nucleic acid comprising the nucleotide sequence set forth in SEQ ID NO: 13.

In another aspect, the invention comprises a significantly purified nucleic acid encoding an H. pylori polypeptide having the amino acid sequence of SEQ ID NO: 87, such as a nucleic acid comprising the nucleotide sequence set forth in SEQ ID NO: 14.

In another aspect, the invention comprises a significantly purified nucleic acid encoding an H. pylori polypeptide having the amino acid sequence of SEQ ID NO: 88, such as a nucleic acid comprising the nucleotide sequence set forth in SEQ ID NO: 15.

In another aspect, the invention includes a significantly purified nucleic acid encoding an H. pylori polypeptide having the amino acid sequence of SEQ ID NO: 89, such as a nucleic acid comprising the nucleotide sequence set forth in SEQ ID NO: 16.

In another aspect, the invention comprises a significantly purified nucleic acid encoding a H. polypeptide pylori having the amino acid sequence of SEQ ID NO: 90, such as a nucleic acid comprising the nucleotide sequence set forth in SEQ ID NO: 17.

In another aspect, the invention comprises a significantly purified nucleic acid encoding an H. pylori polypeptide having the amino acid sequence of SEQ ID NO: 91, such as a nucleic acid comprising the nucleotide sequence set forth in SEQ ID NO: 18.

In another aspect, the invention comprises a significantly purified nucleic acid encoding an H. pylori polypeptide having the amino acid sequence of SEQ ID NO: 92, such as a nucleic acid comprising the nucleotide sequence set forth in SEQ ID NO: 19.

In another aspect, the invention comprises a significantly purified nucleic acid encoding an H. pylori polypeptide having the amino acid sequence of SEQ ID NO: 93, such as a nucleic acid comprising the nucleotide sequence set forth in SEQ ID NO: 20.

In another aspect, the invention comprises a significantly purified nucleic acid encoding an H. pylori polypeptide having the amino acid sequence of SEQ ID NO: 94, such as a nucleic acid comprising the nucleotide sequence set forth in SEQ ID NO: 21.

In another aspect, the invention comprises a significantly purified nucleic acid encoding an H. pylori polypeptide having the amino acid sequence of SEQ ID NO: 95, such as a nucleic acid comprising the nucleotide sequence set forth in SEQ ID NO: 22.

In another aspect, the invention comprises a substantially purified /

A 4,444 nucleic acid encoding an H. pylori polypeptide having the amino acid sequence of SEQ ID NO: 96, such as a nucleic acid comprising the nucleotide sequence set forth in SEQ ID NO: 23.

In another aspect, the invention comprises a significantly purified nucleic acid encoding a polypeptide. H. pylori having the amino acid sequence of SEQ ID NO: 97, such as a nucleic acid comprising the nucleotide sequence set forth in SEQ ID NO: 24.

In another aspect, the invention comprises a significantly purified nucleic acid encoding an H. pylori polypeptide having the amino acid sequence of SEQ ID NO: 98, such as a nucleic acid comprising the nucleotide sequence set forth in SEQ ID NO: 25.

In another aspect, the invention comprises a significantly purified nucleic acid encoding. a H. pylori polypeptide having the amino acid sequence of SEQ ID NO: 99, such as a nucleic acid comprising the nucleotide sequence set forth in SEQ ID NO: 26.

In another aspect, the invention comprises a significantly purified nucleic acid encoding an H. pylori polypeptide having the amino acid sequence of SEQ ID NO: 100, such as a nucleic acid comprising the nucleotide sequence set forth in SEQ ID NO: 27.

In another aspect, the invention comprises a significantly purified nucleic acid encoding an H. pylori polypeptide having the amino acid sequence of SEQ ID NO: 101, such as a nucleic acid comprising the nucleotide sequence set forth in SEQ ID NO: 28.

In another aspect, the invention comprises a significantly purified nucleic acid encoding an H. pylori polypeptide having the amino acid sequence of SEQ ID NO: 102, such as a nucleic acid comprising the nucleotide sequence set forth in SEQ ID NO: 29.

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In another aspect, the invention comprises a significantly purified nucleic acid encoding an H. pylori polypeptide having the amino acid sequence of SEQ ID NO: 103, such as a nucleic acid comprising the nucleotide sequence set forth in SEQ ID NO: 30.

In different. In an aspect, the invention comprises a significantly purified nucleic acid encoding an H. pylori polypeptide having the amino acid sequence of SEQ ID NO: 104, such as a nucleic acid comprising the nucleotide sequence set forth in SEQ ID NO: 31.

In another aspect, the invention comprises a significantly purified nucleic acid encoding an H. pylori polypeptide having the amino acid sequence of SEQ ID NO: 105, such as a nucleic acid comprising the nucleotide sequence set forth in SEQ ID NO: 32.

In another aspect, the invention comprises a significantly purified nucleic acid encoding an H. pylori polypeptide having the amino acid sequence of SEQ ID NO: 106, such as a nucleic acid comprising the nucleotide sequence set forth in SEQ ID NO: 33.

In another aspect, the invention comprises a significantly purified nucleic acid encoding an H. pylori polypeptide having the amino acid sequence of SEQ ID NO: 107, such as a nucleic acid comprising the nucleotide sequence set forth in SEQ ID NO: 34.

In another aspect, the invention comprises a significantly purified nucleic acid encoding an H. pylori polypeptide having the amino acid sequence of SEQ ID NO: 108, such as a nucleic acid comprising the nucleotide sequence set forth in SEQ ID NO: 35.

In another aspect, the invention includes a significantly purified nucleic acid encoding an H. pylori polypeptide having the amino acid sequence of SEQ ID NO: 109, such as a nucleic acid comprising the nucleotide sequence set forth in SEQ ID NO: 36.

In another aspect, the invention comprises a significantly purified nucleic acid encoding an H. pylori polypeptide having the amino acid sequence of SEQ ID NO: 110, such as a nucleic acid comprising the nucleotide sequence set forth in SEQ ID NO: 37.

In another aspect, the invention comprises a significantly purified nucleic acid encoding. a H. pylori polypeptide having the amino acid sequence of SEQ ID NO: 111, such as a nucleic acid comprising the nucleotide sequence set forth in SEQ ID NO: 38

In another aspect, the invention comprises a significantly purified nucleic acid encoding an H. pylori polypeptide having the amino acid sequence of SEQ ID NO: 112, such as a nucleic acid comprising the nucleotide sequence set forth in SEQ ID NO: 39

In another aspect, the invention comprises a significantly purified nucleic acid encoding an H. pylori polypeptide having the amino acid sequence of SEQ ID NO: 113, such as a nucleic acid comprising the nucleotide sequence set forth in SEQ ID NO: 40.

In another aspect, the invention comprises a significantly purified nucleic acid encoding an H. pylori polypeptide having the amino acid sequence of SEQ ID NO: 114, such as a nucleic acid comprising the nucleotide sequence set forth in SEQ ID NO: 41

In another aspect, the invention comprises a significantly purified nucleic acid encoding an H. pylori polypeptide having the amino acid sequence of SEQ ID NO: 115, such as a nucleic acid comprising the nucleotide sequence set forth in SEQ ID NO: 42

In another aspect, the invention comprises a substantially purified · vynález vynálezφφφφφφφ · ··· · · · φ·φφφφφφφφφφφφ

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a nucleic acid encoding an H. pylori polypeptide having the amino acid sequence of SEQ ID NO: 116, such as a nucleic acid comprising the nucleotide sequence set forth in SEQ ID NO: 43.

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In another aspect, the invention includes a significantly purified nucleic acid encoding an H.'pylori polypeptide having the amino acid sequence of SEQ ID NO: 117, such as a nucleic acid comprising the nucleotide sequence set forth in SEQ ID NO: 44.

In another aspect, the invention comprises a significantly purified nucleic acid encoding an H. pylori polypeptide having the amino acid sequence of SEQ ID NO: 118, such as a nucleic acid comprising the nucleotide sequence set forth in SEQ ID NO: 45.

In another aspect, the invention comprises a significantly purified nucleic acid encoding an H. pylori polypeptide having the amino acid sequence of SEQ ID NO: 119, such as a nucleic acid comprising the nucleotide sequence set forth in SEQ ID NO: 46.

In another aspect, the invention comprises a significantly purified nucleic acid encoding an H. pylori polypeptide having the amino acid sequence of SEQ ID NO: 120, such as a nucleic acid comprising the nucleotide sequence set forth in SEQ ID NO: 47.

In another aspect, the invention comprises a significantly purified nucleic acid encoding an H. pylori polypeptide having the amino acid sequence of SEQ ID NO: 121, such as a nucleic acid comprising the nucleotide sequence set forth in SEQ ID NO: 48.

In another aspect, the invention comprises a significantly purified nucleic acid encoding an H. pylori polypeptide having the amino acid sequence of SEQ ID NO: 122, such as a nucleic acid comprising the nucleotide sequence set forth in SEQ ID NO: 49.

and.' . ´ / Ύ another aspect, the invention contains significantly, purified? nucleic acid encoding. polypeptide H ·. pylori having. An amino acid sequence of SEQ ID NO: 123, such as a nucleic acid sequence.

'. . and·. ». <i ....... ', ». . . in

"... acid" containing the nucleotide sequence shown in SEQ ID NO: 50.

», --- ¹ / * <

V. -. . ''/' ^S '·. "· I' · - V ,, j ^ ins aspect of the invention includes" substantially purified: -7 _F; 1 i. '7'. ''. , · * ·· i · * Ϊ / “'•'» »'' · '·' r ^? A nucleic acid encoding an H. pylori polypeptide having a _t . the amino acid sequence of SEQ ID NO: 124, as nucleic acid. / acid comprising the nucleotide sequence set forth in SEQ ID NO: 1 ^; 51.

In another aspect, the invention comprises a significantly purified nucleic acid encoding an H. pylori polypeptide having the amino acid sequence of SEQ ID NO: 125, such as a nucleic acid comprising the nucleotide sequence set forth in SEQ ID NO: 52.

In another aspect, the invention comprises a significantly purified nucleic acid encoding an H. pylori polypeptide having. The amino acid sequence of SEQ ID NO: 126 such as 'nucleic · ^r <' · · j /. vi; .

an acid comprising the nucleotide sequence set forth in SEQ ID NO: 53.

In another aspect, the invention comprises a significantly purified nucleic acid encoding an H. pylori polypeptide having the amino acid sequence of SEQ ID NO: 127, such as a nucleic acid comprising the nucleotide sequence set forth in SEQ ID NO: 54.

In another aspect, the invention comprises a significantly purified nucleic acid encoding an H. pylori polypeptide having the amino acid sequence of SEQ ID NO: 128, such as a nucleic acid comprising the nucleotide sequence set forth in SEQ ID NO: 55.

In another aspect, the invention comprises a significantly purified nucleic acid encoding an H. pylori polypeptide having the amino acid sequence of SEQ ID NO: 129, such as a nucleic acid sequence.

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An acid comprising the nucleotide sequence set forth in SEQ ID NO: 56.

In another aspect, the invention comprises a significantly purified nucleic acid encoding an H. pylori polypeptide having the amino acid sequence of SEQ ID NO: 130, such as a nucleic acid comprising the nucleotide sequence set forth in SEQ ID NO: 57.

In another aspect, the invention comprises a significantly purified nucleic acid encoding an H. pylori polypeptide having the amino acid sequence of SEQ ID NO: 131, such as a nucleic acid comprising the nucleotide sequence set forth in SEQ ID NO: 58.

In another aspect, the invention includes a significantly purified nucleic acid encoding an H. pylori polypeptide having the amino acid sequence of SEQ ID NO: 132, such as a nucleic acid comprising the nucleotide sequence set forth in SEQ ID NO: 59.

In another aspect, the invention comprises a significantly purified nucleic acid encoding an H. pylori polypeptide having the amino acid sequence of SEQ ID NO: 133, such as a nucleic acid comprising the nucleotide sequence set forth in SEQ ID NO: 60.

In another aspect, the invention comprises a significantly purified nucleic acid encoding an H. pylori polypeptide having the amino acid sequence of SEQ ID NO: 134, such as a nucleic acid comprising the nucleotide sequence set forth in SEQ ID NO: 61.

In another aspect, the invention comprises a significantly purified nucleic acid encoding an H. pylori polypeptide having the amino acid sequence of SEQ ID NO: 135, such as a nucleic acid comprising the nucleotide sequence set forth in SEQ ID NO: 62.

In another aspect, the invention comprises significantly purified.

a nucleic acid encoding an H. pylori polypeptide having the amino acid sequence of SEQ ID NO: 136, such as a nucleic acid comprising the nucleotide sequence set forth in SEQ ID NO: 63.

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In another aspect, the invention comprises significantly purified. a nucleic acid encoding an H. pylori polypeptide having the amino acid sequence; SEQ. ID'NO: 137, such as a nucleic acid comprising the nucleotide sequence set forth in SEQ ID NO: 64.

In another aspect, the invention comprises a significantly purified nucleic acid encoding an H. pylori polypeptide having the amino acid sequence of SEQ ID NO: 138, such as a nucleic acid comprising the nucleotide sequence set forth in SEQ ID NO: 65.

In another aspect, the invention comprises a significantly purified nucleic acid encoding an H. pylori polypeptide having the amino acid sequence of SEQ ID NO: 139, such as a nucleic acid comprising the nucleotide sequence set forth in SEQ ID NO: 66.

In another aspect, the invention comprises a significantly purified nucleic acid encoding an H. pylori polypeptide having the amino acid sequence of SEQ ID NO: 140, such as a nucleic acid comprising the nucleotide sequence set forth in SEQ ID NO: 67.

In another aspect, the invention comprises a significantly purified nucleic acid encoding an H. pylori polypeptide having the amino acid sequence of SEQ ID NO: 141, such as a nucleic acid comprising the nucleotide sequence set forth in SEQ ID NO: 68.

In another aspect, the invention comprises a significantly purified nucleic acid encoding an H. pylori polypeptide having the amino acid sequence of SEQ ID NO: 142, such as a nucleic acid comprising the nucleotide sequence set forth in SEQ ID NO: 69.

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In another aspect, the invention comprises a significantly purified nucleic acid encoding an H. pylori polypeptide having the amino acid sequence of SEQ ID NO: 143, such as a nucleic acid comprising the nucleotide sequence set forth in SEQ ID NO: 70.

In another aspect, the invention comprises a significantly purified nucleic acid encoding an H. pylori polypeptide having the amino acid sequence of SEQ ID NO: 144, such as a nucleic acid comprising the nucleotide sequence set forth in SEQ ID NO: 71.

In another aspect, the invention comprises a significantly purified nucleic acid encoding an H. pylori polypeptide having the amino acid sequence of SEQ ID NO: 145, such as a nucleic acid comprising the nucleotide sequence set forth in SEQ ID NO: 72.

In another aspect, the invention comprises a significantly purified nucleic acid encoding an H. pylori polypeptide having the amino acid sequence of SEQ ID NO: 146, such as a nucleic acid comprising the nucleotide sequence set forth in SEQ ID NO: 73.

Particularly preferred is an isolated nucleic acid comprising a nucleotide sequence encoding a H. pylori cell envelope polypeptide or fragment thereof. Such nucleic acid is selected from the group consisting of SEQ ID NO: 3, SEQ ID NO: 25, SEQ ID NO: 48, SEQ ID NO: 16, SEQ ID NO: 10, SEQ ID NO: 45, SEQ ID NO: 35, SEQ ID NO: 37, SEQ ID NO: 7, SEQ ID NO: 39, SEQ ID NO: 55, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 28, SEQ ID NO: 30, SEQ ID NO:

52, SEQ ID NO: 54, SEQ ID NO: 56, SEQ ID NO: 58, SEQ ID NO: 1,

SEQ ID NO: 42, SEQ ID NO: 14, SEQ ID NO: 43, SEQ ID NO: 11, SEQ

SEQ ID NO: 71, SEQ ID NO: 17, SEQ ID NO: 57, SEQ ID NO: 5, SEQ ID NO:

6, SEQ ID NO: 8 and SEQ ID NO: 21.

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

In different. In an embodiment, the envelope polypeptide is H. pylori or its. a fragment of H.ypylori outer membrane polypeptide, or a fragment thereof encoded by a nucleic acid selected from the group consisting of SEQ ID NO: 16, SEQ ID NO: 10, SEQ ID NO: 45, SEQ ID NO: 35, SEQ ID NO: 37, SEQ ID NO: 7, SEQ ID NO: 39, SEQ ID NO 55, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 28, SEQ ID NO: 30, SEQ ID NO: 52, SEQ ID NO: 54, SEQ ID NO: 56, SEQ ID NO: 58, SEQ ID NO: 1, SEQ ID NO: 42, SEQ ID NO: 14, SEQ ID NO: 43, SEQ ID NO 11, and SEQ ID NO. : 71,

In another embodiment, the outer envelope polypeptide of a H. pylori cell or fragment thereof is an H. pylori polypeptide having a terminal phenylalanine residue and a C-terminal tyrosine moiety, or a fragment thereof encoded by a nucleic acid selected from the group consisting of SEQ ID NO: 1, SEQ ID NO SEQ ID NO: 14, SEQ ID NO: 43, SEQ ID NO: 11, and SEQ ID NO: 71.

In another embodiment, the outer envelope polypeptide of a H. pylori cell or fragment thereof is a H. pylori polypeptide having a terminal phenylalanine residue or fragment thereof encoded by a nucleic acid selected from the group consisting of SEQ ID NO: 16, SEQ

SEQ ID NO: 45, SEQ ID NO: 35, SEQ ID NO: 37, SEQ ID NO: 7, SEQ ID NO

39, SEQ ID NO: 55, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 28,

SEQ ID NO: 30, SEQ ID NO: 52, SEQ ID NO: 54, SEQ ID NO: 56, and SEQ

ID NO: 58.

Particularly preferred is an isolated nucleic acid comprising a nucleotide sequence encoding a secreted H. pylori polypeptide or fragment thereof. Such a nucleic acid is selected from ·· ····

The group consisting of SEQ ID NO: 72, SEQ ID NO: 32, SEQ ID NO:

51, SEQ 1 ID ΝΟ- 2, SEQ SEQ ID NO: 4, SEQ I ID NO: 13, 1 SEQ ID 22: 22, SEQ ID NO: 29, SEQ SEQ ID NO: 31, SEQ ID NO: ' 33, SEQ ID NO: 34; .SEQ ID > NO: 36, SEQ ID NO: 38, SEQ ID NO: 40, SEQ ! ID NO: 41 ,. SEQ ID-NO: 44, SEQ ID NO: 46 SEQ ID NO: 49 SEQ ID NO NO: 53, SEQ ID NO: '59, ^! SEQ ID NO. 61, SEQ SEQ ID NO: 62, SEQ .ID NO: 65, SEQ ID NO: 66, SEQ ID NO: 67 and SEQ ID NO NO: 68.

Particularly preferred is an isolated nucleic acid comprising a nucleotide sequence encoding a H. pylori cell polypeptide or fragment thereof. Such nucleic acid is selected from the group consisting of SEQ ID NO: 12, SEQ ID NO: 15, SEQ ID NO: 20, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 26, SEQ ID NO: 27, SEQ ID NO: 47, SEQ ID NO: 50, SEQ ID NO: 60, SEQ ID NO: 64, SEQ ID NO: 69, SEQ ID NO: 70, and SEQ ID NO: 73.

Particularly preferred is a purified or isolated H. pylori cell envelope polypeptide or fragment thereof, wherein the polypeptide is selected from the group consisting of SEQ ID NO: 76, SEQ ID NO: 98,

SEQ ID NO: 121, SEQ ID NO: 89, SEQ ID NO: 83, SEQ ID NO: 118, SEQ ID NO: 108, SEQ ID NO: 110, SEQ ID NO: 80, SEQ ID NO: 112, SEQ ID NO.

NO: 128, SEQ ID NO: 91, SEQ ID 103, SEQ ID NO: 125 SEQ [ID NO 131, SEQ NO NO: 74, SEQ ID NO: 116, SEQ NO ID: 84, SEQ ID NO: 130, SEQ NO NO: 78, SEQ ID NO:

NO: 92, SEQ ID NO: 101, SEQ ID NO:

127, SEQ ID NO SEQ ID NO: 129 115, SEQ ID NO: 87, SEQ ID NO: 144, SEQ ID NO: 90, SEQ ID NO: 79, SEQ ID NO: 81 a SEQ ID NO: 94

In another embodiment, the H. pylori cell envelope polypeptide is an H. pylori inner membrane polypeptide or fragment thereof selected from the group consisting of SEQ ID NO: 76, SEQ ID NO: 98 and SEQ ID NO: 121.

In another embodiment, the cell envelope polypeptide is H. pylori.

outer membrane polypeptide. pylori or a group thereof consisting of SEQ ID NO: 89, a SEQ fragment selected

SEQ ID NO: 83;

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NO: 118, SEQ ID NO: 108, SEQ ID NO: 11, SEQ .ID. NO: 128, SEQ ID 101, .SEQ ID NO: 103, SEQ. ID NO: 129, SEQ. ID NQ: 131, SEQ ID NO:

.87, SEQ ID NO: 116, SEQ ID NO: 84, and SEQ ID NO: 130. '

NO: 110, SEQ ID NO: 80, SEQ ID NO: 91, SEQ ID NO: .92, SEQ ID NO: .125, SEQ ID NO: 127, SEQ ID NO:

74, SEQ. ID NO: 115. SEQ. ID NO: '

SEQ ID NO: 144. SEQ ID NO: 90 ^A. . . t.

In another embodiment, the outer membrane polypeptide of H. pylori or a fragment thereof is H. pylori having a terminal phenylalanine residue and a C-terminal tyrosine moiety or a fragment thereof selected from the group consisting of SEQ ID NO: 7A, SEQ ID NO: 4L15, SEQ. SEQ ID NO: 87, SEQ ID NO: 116, SEQ ID NO: 84 and SEQ ID NO: 144.

In another embodiment, the polypeptide is; an outer H. pylori membrane or fragment thereof of H. pylori having a terminal phenylalanine residue or fragment thereof selected from the group consisting of SEQ ID NO: 89, SEQ ID NO: 118, SEQ ID NO: 108,

SEQ ID NO: 110, SEQ ID NO: 80, SEQ ID NO: 112, SEQ ID NO: 128,

SEQ ID NO: 91, SEQ ID NO: 92, SEQ ID NO: 101, SEQ ID NO: 103, SEQ ID NO: 125, SEQ ID NO: 127, SEQ ID NO: 129, SEQ ID NO: 131.

Particularly preferred is a purified or isolated secreted H. pylori polypeptide or fragment thereof, wherein the polypeptide is selected from the group consisting of SEQ ID NO: 145, SEQ ID NO: 105, SEQ ID NO: 124, SEQ ID NO: 75, SEQ ID NO. NO: 77, SEQ ID NO: 82, SEQ ID NO:

86, SEQ: ID NO: 95, SEQ and NO: 102, SEQ IE * NO: 104, SEQ »NO: 106, SEQ ID NO: 107, SEQ ID NO: 109 SEQ ID NO: 111, SEQ ID NO: 113, SEQ ID NO: 114, SEQ ID NO: 117 SEQ ID NO: 119, SEQ ID NO: 122, SEQ ID NO: 126, SEQ ID NO: 132 SEQ ID NO: 134, SEQ ID NO: 135, SEQ ID NO: 136, SEQ ID NO: 138 SEQ ID NO: 139, SEQ ID NO:

··· 000 · • 0 0000

000

0 *

140 and SEQ ID NO: 141.

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Particularly preferred is a purified or isolated H. pylori cell polypeptide or fragment thereof, wherein the polypeptide is selected from the group consisting of SEQ ID NO: 85, SEQ ID NO: 88, SEQ ID NO: 93, .SEQ.-ID '. NO: 96, SEQ ID NO: 97, SEQ ID NO: 99, SEQ ID NO:

100, SEQ ID NO: 120, SEQ ID NO: 123, SEQ ID NO: 133, SEQ ID NO:

137., SEQ ID NO: 142, SEQ ID NO: 143, and SEQ ID NO: 146.

In another aspect, the invention relates to any H. pylori polypeptide or a nucleic acid encoding such a polypeptide belonging to a group of H. pylori polypeptides as defined above.

In another aspect, the invention relates to nucleic acids capable of binding to H. pylori mRNA. Such a nucleic acid may act as an antisense nucleic acid to control the translation of H. pylori mRNA. In another aspect, the invention relates to nucleic acids that are capable of specifically binding to a H. pylori nucleic acid. These nucleic acids are also referred to herein as complementary nucleic acids and can be used as probes and capture agents.

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

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

In another aspect, the invention relates to a method for producing antibodies. · T

against H. pylori polypeptides that specifically bind to polypeptides Ή. pylori. Such antibodies are useful as reagents in immunoassays to evaluate the frequency and distribution of H. pylori-specific antigens. In another aspect, the invention relates to a method for producing vaccines for immunizing individuals against H. pylori. The vaccination technique comprises: immunizing a subject with at least one H. pylori polypeptide of the present invention, for example, a surface or secreted polypeptide, or an active portion thereof, and a pharmaceutically acceptable carrier. Such vaccines have therapeutic and / or prophylactic uses.

In another aspect, the invention includes a method for making a vaccine comprising a modified immunogenic H. pylori polypeptide, for example a surface or secreted polypeptide or an active portion thereof, and a pharmaceutically acceptable carrier. , - /

In another aspect, the invention relates to a method for testing compounds, for example polypeptides, for example, a fragment of a host cell polypeptide, for the ability to bind an H. pylori polypeptide.

The method comprises: contacting the test compound with an H. pylori polypeptide and determining whether the compound binds or otherwise interacts with the H. pylori polypeptide. Compounds that bind to H. pylori are candidates for bacterial life cycle activators or inhibitors. These assays can be performed in vivo or in vitro.

In another aspect, the invention relates to a method for testing compounds, for example polypeptides, for example, a fragment of a host cell polypeptide, for the ability to bind to H. pylori nucleic acid, for example, DNA or RNA. The method comprises: contacting the test compound with H. pylori nucleic acid and determining the ·

• 9 9 9 9 · 99 9 99 9

The amino acid sequence of 1, 2, 3, 5, 10, or more residues of the sequence of the present invention included in the sequence listing. However, the differences are that the H. pylori polypeptide exhibits the biological activity of the H. pylori polypeptide, for example, the H. pylori polypeptide retains the biological activity of the native H. pylori polypeptide.

In preferred embodiments, the polypeptide comprises all or a fragment of the amino acid sequence of the present invention included in the sequence listing; dabbling in reading frame, to additional amino acid residues, preferably to residues encoded by genomic DNA 5 'or 3 ¹ to genomic DNA encoding a sequence of the invention contained in the Sequence Listing.

In yet another preferred embodiment, the H. pylori polypeptide is a recombinant polypeptide having a first portion of an H. pylori polypeptide and a second portion of a polypeptide, for example, a polypeptide having an amino acid sequence that is not related to H. pylori. For example, the second polypeptide moiety may be any glutathione-S-transferase, DNA-binding domain, or polymerase activating domain. In a preferred embodiment, the fusion protein can be used in a two-hybrid assay.

Polypeptides of the present invention include those polypeptides that result from alternative transcription, alternative RNA splicing, and alternative translational and post-translational processing.

The invention also provides an immunogenic component comprising at least one H. pylori polypeptide in an immunogenic composition; wherein the immunogenic component can elicit an immune response specific for an H. pylori polypeptide, for example, a humoral response, an antibody response, or a cellular response. In preferred embodiments, it comprises

an immunogenic component of at least one antigenic determinant from a polypeptide of the present invention that is included in the sequence listing.

In another aspect, the invention also includes a significantly purified nucleic acid having a nucleotide sequence encoding a H. pylori polypeptide. In preferred embodiments, the encoded polypeptide has: biological activity; an amino acid sequence at least 60%, 70%, 80%, 90%, 95%, 98% or 98% identical or homologous to the amino acid sequence of the present invention shown in the sequence listing; an amino acid sequence substantially the same as the amino acid sequence of the present invention included in the sequence listing; a length of at least 5, 10, 20,

1-10 or 150 amino acids; it comprises at least 5, preferably 10, more preferably at least 20, preferably at least 50, 100, or 150 contiguous amino acid residues of the present invention included in the sequence listing.

In preferred embodiments, the nucleic acid of the present invention is a nucleic acid included in the sequence listing; the nucleic acid has at least 60%, 70%, 80%, 90%, 95%, 98% or 99% homology to the nucleic acid sequence of the present invention included in the sequence listing.

In a preferred embodiment, the encoded H. pylori polypeptide differs (e.g., by amino acid substitution, addition, or deletion of at least one amino acid residue) in the amino acid sequence of 1, 2, 3, 5, 10, or more residues from the sequence of the present invention contained in the sequence listing. However, the differences are that the encoded H. pylori polypeptide exhibits the biological activity of the H. pylori polypeptide, for example, the encoded H. pylori polypeptide retains the biological activity of the native H. pylori polypeptide.

In preferred embodiments, the encoded polypeptide / all or fragment of an amino acid sequence of the present invention is contained in the sequence listing; fused, in a reading frame, to other amino acid residues, preferably residues encoded by 5 'or 3' genomic DNA, to the genomic DNA coding sequences of the present invention included in the list. sequences. ~ ·

In a preferred embodiment, the H. pylori nucleic acid comprises a regulatory sequence, for example, at least one transcriptional promoter or transcription enhancer, in operable linkage to the H. pylori gene sequence, so that the H. pylori gene sequence is suitable for expression in recombinant host cells.

In yet another preferred embodiment, the nucleic acid encoding the H. pylori polypeptide of the present invention hybridizes under stringent conditions to a nucleic acid probe corresponding to at least 8 contiguous nucleotides of the present invention that are listed in the sequence listing; preferably corresponding to at least 12 contiguous nucleotides of the present invention that are listed in the sequence listing; preferably corresponding to at least 20 contiguous nucleotides of the present invention that are listed in the sequence listing; preferably corresponding to at least 40 contiguous nucleotides of the present invention that are listed in the sequence listing.

In a preferred embodiment, the nucleic acid encodes a peptide that differs in at least one amino acid residue from the sequences of the present invention included in the sequence listing.

In a preferred embodiment, the nucleic acid differs in at least one nucleotide from the nucleotide sequences of i

4.

 The present invention included in the sequence listing that encodes the amino acids of the present invention included in the sequence listing.

In another aspect, the invention includes: a vector comprising a nucleic acid that encodes an H. pylori polypeptide or a variant H. pylori polypeptide as described herein; a host cell transfected with a vector; and a method for producing a recombinant H. pylori polypeptide or variant H. pylori polypeptide that comprises culturing cells, for example, in: a cell culture medium, and isolating the H. pylori polypeptide or variant H. pylori, for example, from cells or from a cell culture medium.

In another aspect, the invention relates to a purified recombinant nucleic acid having at least? 50%, 60%, 70%, 80%, 90%, 95%,

98% or 99% homology to the sequence of the present invention included in the sequence listing. , ¹ »· ', i

The invention also includes a probe or primer that comprises a significantly purified oligonucleotide. The oligonucleotide comprises a region of the nucleotide sequence that hybridizes under stringent conditions to at least 8 contiguous nucleotides of the coding or antisense sequences of the present invention listed in the Sequence Listing, or a natural mutant thereof. In a preferred embodiment, a labeling moiety is attached to the probe or primer. For example, the labeling moiety may be a radioisotope, a fluorescent moiety, an enzyme, and / or an enzyme cofactor. Preferably, the oligonucleotide is at least 8 and less than 10, 20, 30, 50, 100, or 150 nucleotides in length.

The invention also includes an isolated H. pylori polypeptide that is encoded by a nucleic acid that hybridizes under stringent conditions

... conditions for the nucleic acid given in the sequence listing.

The invention also encompasses nucleic acids, for example RNA or DNA, encoding a polypeptide of the present invention. These include double-stranded nucleic acids as well as coding and antisense single strands.

The H. pylori strain whose genomic sequences were sequenced was deposited with the American Type Culture Collection (ATCC # 55679; deposited by Genome Therapeutics Corporation, 100 Beaver Street, Waltham, MA 02154) as an HP-J99 strain.

The invention includes: allelic variations; natural mutants; induced mutants; proteins encoded by DNA that hybridize under conditions of high or low stringency to a nucleic acid that encodes a polypeptide of the present invention included in the sequence listing (for definition of high and low stringency conditions, see Current Protocols in Molecular Biology, John Wiley &

New York, 1989, 6.3.1-6.3.6 and 6.4.1-6.4.10, incorporated herein by reference); and polypeptides that specifically bind to an antiserum to H. pylori polypeptides, particularly to an antiserum to the active site or binding domain of the H. pylori polypeptide. The invention also includes fragments, particularly biologically active fragments. These and other polypeptides are also referred to as H. pylori analogs or variants.

The putative functions of several H. pylori polypeptides of the present invention have been determined and are listed in Table 1.

Accordingly, the present invention also encompasses the use of H. pylori polypeptides based on identifying these functions as well as other functions described herein.

• · β e · t: · · · · ·

- - «····

Further, the present invention comprises H. pyloricharacterized polypeptides in Table 1 below, including: H. pylori cell envelope proteins; secreted H. pylori proteins; and H. pylori cell proteins. Proteins belonging to these groups were identified by screening for BLAST homology and screening for secretory signals or transmembrane protein motives Polypeptides significantly homologous to the polypeptides of Table If the homologues listed in Table <1 are also considered. ¹

• · · ····

Table 1

[j ORF - Name and group nt SeqlD aa SeqlD | A. Cell envelope A.1 I Internal membrane proteins · 02ge11622 23494043 f1 6 3 76 hp5p15212 13095752 c3 36 25 98 06ep30223_20173437_f1_37 48 121 A. 2 External membrane proteins 05ee10816_14495437_f2_13. 10 83 A.2.1 terminal phe residue 06ep11509 35954752J2 1 16 89 06ep 10615 14495437 f3 47 45 118 03ae10804 14495437 c2 38 35 108 05ae30220 917200 c3 172 37 110 04cp 11202 23646885 f2 26 7 80 05ep10815 16131925 c2 97 39 112 09cp61003 5860877 f2 23 55 128 09ae10512 48768 c3 67 18 91 09cp11003 5860877 f3 7 19 Dec 92 hp6e12267 30478562 f3 33 28 101 06cp30603 34174212 c3 71 30 '103 09cp10224 1962590 f3 31 52 125 09cp61003 30478562 c3 106 54 127 11ae80818 10553192 f2 16 56 129 11ee11408_10584582_c3_51 58 131 A.2.2 terminal phe residue and C- C- and terminal tyrosine grouping 01ae12001 116018 c2 40 1 74 06ap10609 116018 c3 50 42 115 06cp30603 4687507 f1 9 14 87 06cp30603 4687507 f1 7 43 116 05ee 10816 36126938 f3 16 11 84 01cp20708_4960952_c1_43 71 144 A. 3 Homology 07ap80601 5083193 f3 8 17 90 11ap20714_4797137_f3_45 57 130 A.4 (Other cell envelope proteins 04ap12016 25501501J1 1 5 78 04cp 11202 20415937 f2 25 6 79 04ee11108 3906963 f1 7 8 8Ϊ 29ep10720_25501501_c2_33 21 94 Secured proteins 5 hp3e 10342 22448587 c2 14 72 145 hp5p15212 24276587 f1 2 32 105 09ce10413 35336707 f2 9 51 124

01ae12001 32462543 c2 43 2 75 03ee11215 1416312 c3 35 4 77 05ae30220 14570443 c2 94 9 82 06cp30603 2772578 c1 46 13 86 29ep10720 289077 f2 12 22nd 95 03ee11215 22542803 f1 7 29 102 09a, e10512 3166040 c1 40 > 31 104 01ce11104 10742963 c2 11. 33 106 02ge10116 36335436 f3 66 34 .107 04ep41903 11876461 f1 4 36 , 109 05ce10208 23631292 f1 7 38 , 111 05ep10815 22447252 c3 110 40 113 05ep10815 30283516 c3 109 41 114 106ee30709 33851038 c3 30 44 117 06ep11202 21687842 c3 35 46 119 06ep30223 2774062 f1 33 49 122 09cp10713 23912707 c1 26 53 126 11ee11408 4882318 f3 24 59 132 hp4e13394 5908553 f 1 1 61 134 hp4e53394 1416312 c3 119 62 135 hp5e15211 24328910 c3 38 63 136 hp6p10606 23493756 cE21 65 138 hp6p22217 23564012 f1 5 66 139 hp6p22217 272058 f1 2 67 .140 hp6p22217_2922143_f2_9 '. .68 141 Other cellular proteins 06ap11119 14726542 f3 21 12 * 85 06ee10709 6136430 c1 11 15 Dec . . 88 12ap10605 14094816 c1 5 20 May 93 hp2p10272 34042518 f1 2 23 96 hp5e15211 25411557 c1 23 24 97 hp5p15641 3907968J1 3 26 99 hp6e10967 657638 f3 9 27 Mar: 100 ALIGN! 06ep11202 4569693 c2 28 47 120 06ep30223 3930468 c1 110 50 123 hp2e10911 960952 c2 86 60 133 hp6p10509 14642217 c2 17 64 137 hp6p80503 20964382 f2 11 69 142 hp7e10192 5917593 f1 2 70 143 hp6p10509 14642217 c3 25 73 146

(In Table 1, nt means the nucleotide sequence identification number and aa means the amino acid sequence identification number)

·· ··

Definition.:

Terms Purified Polypeptide and Isolated Polypeptide a. The substantially pure polypeptide preparation are;, ^am of f ^n, and thus useful as jsou.zde ⁵ used means a polypeptide free of other proteins, lipids, ·, and nucleic acids with which it naturally occurs. Preferably, the polypeptide is also separated from the constituents, e.g., antibodies or gel, e.g., polyacrylamide, which have been used to purify it. Preferably, the polypeptide constitutes at least 10, 20, 50, 70, 80, or 90% of the dry weight of the purified composition. Preferably, the composition comprises: sufficient polypeptide for protein sequencing; at least 1, 10 or 100 µg of polypeptide; at least 1, 10 or 100 mg of polypeptide. Furthermore, the terms purified polypeptide and isolated polypeptide and significantly purified polypeptide preparation as used herein refer to both a naturally occurring polypeptide and a polypeptide produced by the recombinant DNA technique as described herein.

For example, the isolated or purified protein or biologically active portion thereof is substantially free of cellular material or other contaminating proteins from the cells or tissues from which the H. pylori protein is derived, or substantially free of chemical precursors or other chemical compounds when synthesized. chemical. Substantially cell-free refers to preparations of the H. pylori protein in which the protein is separated from the cellular components of the cells from which it is isolated or in which it is recombinantly produced. In one embodiment, the substantially cell-free term refers to preparations of H. pylori protein having less than about 30% (dry weight) of non-H. pylori proteins (also referred to herein as contaminating proteins), preferably less than about

20% of non-H, pylori, more preferably less than about 10% of non-H. pylori, and most preferably less than about

·· ΒΒΒΒ

5% of non-H. pylori proteins. If the H. pylori protein or an active portion thereof is produced recombinantly, then it is also preferably substantially free of the culture medium, i.e. the culture medium represents less than about 15%. about 20%, preferably less than about 10%, and most preferably at least about 5% by volume of the protein preparation.

Substantially free of chemical precursors or other chemical compounds refers to preparations of H. pylori protein in which the protein is separated from chemical precursors or other chemical compounds used in protein synthesis.

In one embodiment, substantially free of chemical precursors or other chemical compounds refers to preparations of an H.pylori protein having less than about 30% (dry weight) chemical precursors or other chemical compounds not belonging to H. pylori, more preferably less than about 20% chemical precursors, or other chemical compounds not belonging to H. pylori, more preferably less than about 10% of chemical precursors or other chemical compounds not belonging to H. pylori, and most preferably less than about 5% of chemical precursors or other chemical compounds not belonging to H. pylori

A purified cell preparation denotes, 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 at least 10% and preferably 50% of said cells.

A purified or isolated or significantly purified nucleic acid, for example a substantially purified DNA, (terms are interchangeable) is a nucleic acid selected from one or both of: a nucleic acid that does not immediately adjoin both coding sequences immediately adjacent (i.e., 5'-). end and at the 3'-end) in the natural genome of the organism from which

IN

0 · · 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 • 0 e · • 0 · • 0 • · 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 é • « • 0

whether the compound binds or otherwise interacts with the H. pylori polypeptide. Compounds that bind to H. pylori are candidates for bacterial life cycle activators or inhibitors. These assays may be performed in vivo or in vitro.

The invention further relates to a H. pylori polypeptide, preferably significantly purified polypeptide přípravků formulations. pylori or a recombinant H. pylori polypeptide. In preferred embodiments, the polypeptide has:. biological activity; an amino acid sequence at least 60%, 70%, 80%, 90%, 95%, 98% or 98% identical or homologous to the amino acid sequence of the present invention listed in the Sequence Listing, preferably has about 65% sequence identity to the amino acid sequence of the present of the invention listed in the Sequence Listing, and preferably has about 92% to 99% sequence identity with the amino acid sequence of the present invention listed in the Sequence Listing; an amino acid sequence substantially the same as the amino acid sequence of the present invention included in the sequence listing;

100 or 150 amino acids; it comprises at least 5, preferably 10, more preferably at least 20, preferably at least 50, 100 or, 150 contiguous amino acid residues of the present invention included in the sequence listing. In yet another preferred embodiment, the invention also includes an amino acid sequence that differs in sequence identity by about 7% to 8% from the H. pylori amino acid sequence of the present invention contained in the sequence listing.

In preferred embodiments, the H. pylori polypeptide encoded by the nucleic acid of the present invention is contained in a sequence listing or a nucleic acid having at least 60%,

70%, 80%, 90%, 95%, 98% or 99% homology to the nucleic acid of the present invention included in the sequence listing.

In a preferred embodiment, a particular H. pylori polypeptide differs in

A <

jemucleic acid obtained; or a nucleic acid that is significantly purified from the nucleic acids with which it occurs in the organism from which the nucleic acid is derived. The term includes, for example, recombinant DNA that is inserted into a vector, for example, an autonomously replicating vector. plasmid or virus, or into prokaryotic or genomic DNA? eukaryotic organism, or which exists as a separate molecule (for example, a cDNA or genomic DNA fragment produced by PCR or by restriction endonuclease processing) independent of other DNA sequences. Significantly purified DNA also includes recombinant DNA that is part of a hybrid gene encoding additional H. pylori DNA sequences.

As used herein, a portion of a sequence means a nucleic acid representing a contiguous strand of the genomic sequence of an organism.

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

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

As used herein, the term complementary nucleic acid sequence is an antiparallel or antisense sequence that participates in the term &quot; 33 &quot;

9 Β '' 9 '· Β 9 Β · Β • Β Β · ΒΒΒΒ

ΒΒΒ · ’· Β 'Β Β · ΒΒΒ ΒΒΒ

Β Β ΒΒΒ Β Β

ΒΒ ΒΒ Β ΒΒ ΒΒ

Watson-Crick-pairing craves the original sequence.

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

As used herein, a probe refers to a nucleic acid, a peptide, or other chemical entity that specifically binds to a molecule of interest. Probes are often attached or markings can be attached to them. A label is a chemical moiety that can be detected. Typical labels are dyes, radioisotopes, luminescent reagents and chemiluminescent groups, fluorophores, enzymes, clotting agents, amplification sequences, and the like. Similarly, a nucleic acid, peptide or other chemical entity that specifically binds to a desired molecule and immobilizes such a molecule is referred to as a capture ligand. The capture ligands are usually associated with or capable of associating with carriers such as hitrocellulose, glass, nylon membranes, beads, particles, and the like: The specificity of the hybridization depends on conditions such as base pairing of nucleotides, temperature and salt concentration in the reaction. These conditions will be determined by those skilled in the art by routine experimentation.

Homology refers to sequence similarity or sequence identity between two polypeptides or two nucleic acid molecules. If the position in both sequences being compared is occupied by the same base or amino acid monomeric subunit, for example when the position in each of the two DNA molecules is occupied by adenine, then the molecules in that position are homologous. The percent homology between two sequences is the number of corresponding or homologous positions in the two sequences divided by the number of aligned positions x 100. For example, if 6 of the 10 positions in the two sequences match or are homologous, the two sequences have 60% homology. For example, the DNA sequences ATTGCC and TATGGC have 50% homology.

· *.

• 9 9 9 9 9 9 9 9 9 9 9 9 9

Λ99 9999 99 '9

99 9 9 9

9 9 '··· «·· • · ·· ··

Generally, a comparison is made when the two sequences are aligned to have the highest homology.

• T ·. Nucleic acids are hybridizable to each other if at least one nucleic acid strand can be thermally bound to the other nucleic acid under defined stringency conditions. The stringency of the hybridization is determined by: (a) the temperature at which hybridization and / or washing is performed; and (b) the ionic concentration and polarity of the hybridization and wash solutions · Hybridization requires that two nucleic acids contain complementary sequences; however, depending on the stringency of the hybridization, errors may be tolerated. Typically, hybridization at high stringency (such as a 0.5X SSC solution at 65 ° C) requires the sequences to be substantially completely homologous. Medium stringency conditions (such as 2X SSC at ° C) and low stringencies (such as 2X SSC at 55 ° C) require a correspondingly lower overall complementarity between hybridizing sequences. (1X SSC is 0.15 M NaCl, 0.015 M Na citrate). A preferred, non-limiting example of stringent hybridization conditions is hybridization in 6X sodium chloride / sodium citrate (SSC) at 45 ° C, followed by one or more washes in 0.2X SSC, 0.1% SDS at 50-65 ° C.

The terms peptides, proteins and polypeptides are interchangeable.

As used herein, the term surface protein refers to all proteins available on the surface, for example, outer and inner membrane proteins, cell wall adhering proteins, and secreted proteins.

A polypeptide has the biological activity of an H. pylori polypeptide when it has one, two, and preferably more of the following properties:

(l) if expressed during H. pylori infection, it may induce

• 0 9 «

9 '9

0099 '· 0 · 0 or mediate binding of H. pylori to cells ,; (2) has an enzymatic-activity, structural or regulatory function characteristic of the H. pylori protein; (3) the gene encoding it can replace a lethal mutation in the H. pylori gene; or (4) is immunogenic in the subject. A polypeptide has biological activity when it is an antagonist, agonist or super-agonist of a polypeptide having the above properties.

A biologically active fragment or analog is one having in vivo or in vitro activity that is characteristic of the H. pylori polypeptides of the present invention included in the sequence listing, or other natural H. pylori polypeptides, for example, one or more biological activities that are described herein. Particularly preferred are fragments that exist in vivo, for example, fragments that result from post-transcriptional processing or from translation of alternatively spliced RNA. Fragments include those expressed in native or endogenous cells, as well as those produced in expression systems, for example, CHO cells. Since peptides such as H. pylori polypeptides often have different physiological properties, and because properties can also be attributed to different parts of the molecule, a useful fragment of H. pylori or an H. pylori analogue is one that exhibits biological activity in any biological test for H. pylori activities. Most preferred is a fragment or analog having 10%, preferably 40%, and most preferably 60%, 70%, 80% or 90% H. pylori activity in an in vivo or in vitro assay.

Analogs differ from native H. pylori polypeptides in amino acid sequence or non-sequence methods, or both. Non-sequence modifications include acetylation, methylation, phosphorylation, carboxylation, or glycosylation. Preferred analogs include H. pylori polypeptides (or biologically active fragments thereof) whose sequence differs from the native t.

Sequences of one or more conserved amino acid substitutions, deletions, or insertions that do not significantly reduce the sequence of one or more conserved amino acid substitutions, deletions, or insertions. the biological activity of the H. pylori polypeptide. Conservative substitutions typically include substitution of one amino acid with another amino acid with similar characteristics / for example, substitutions in the following groups: valine, glycine; glycine, alanine; valine, isoleucine, leucine; aspartic acid, glutamic acid; asparagine, glutamine; serine, threonine; lysine, arginine; and phenylalanine, tyrosine. Other conservative substitutions are listed in Table 2, below.

"Table 2: Conservative amino acid substitutions

4 · - »>

4 4 4 4 4

Aminoacid Code .Substitution of any of Alanin and: · D-Ala, Gly, β-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 Ásparagin, N D-Asn, Asp, D-Asp, Glu, D-Glu, Gln, D-Gln Acid D D-Asp, D-Asn, Asn, Glu, D-Glu, Gln, D-Gln asparagová Cysteine C D-Cys, S-Me-Cys, Met, D-Met, Thr, D-Thr Glutamine Q D-Gln, Asn, D-Asn, Glu, D-Glu, Asp, D-Asp Acid E D-Glu, D-Asp, Asp, Asn, D-Asn, Gln, D-Gln glutamic Glycine G Ala, D-Ala, Pro, D-Pro, [beta] -Ala, Acp Isoleucine AND D-Ile, D-Val, D-Val, Leu, D-Leu, Met, D-Met Leucin L D-Leu, Val, D-Val, Leu, D-Leu, Met, D-Met Lysine TO D-Lys, Arg, D-Arg, homo-Arg, D-homo-Arg, Met, D-Met, Ile, D-Ile, Orn, D-Orn Methionine M D-Met, S-Me-Cys, Leu, D-Leu, Val, D-Val Phenylalanine F D-Phe, Tyr, D-Thr, L-Dopa, His, D-His,

Proline

Serin

Threonine

Tyrosine

Valin

Trp, D-Trp, Trans-3,4 or 5-phenylproline, cis-3,4 or 5-phenylproline β D-Pro, L-1-thiazolidine-4-carboxylic acid, D- or

L-1-oxazolidine-4-carboxylic acid with D-Ser, Thr, D-Thr, allo-Thr, Met, D-Met,

Met (O), D-Met (0), L-Cys, D-Cys, D-Thr, Ser, D-Ser, allo-Thr, Met, D-Met,

Met (0), D-Met (0), Val, D-Val

Y-D-Tyr, Phe, D-Phe, L-Dopa, His, D-His

In D-Val, Leu, D-Leu, Ile, D-Ile, Met, D-Met

Other analogs of the present invention are analogs with modifications that enhance the stability of the peptide; such analogs may comprise, for example, one or more non-peptide bonds (instead of peptide bonds) in the peptide sequence. Also included are: analogs that contain residues other than natural L-amino acids, ⁵ for example D-amino acids or non-natural or synthetic amino acids, for example β or τ amino acids; and cyclic analogs.

The term fragment as used herein for an H. pylori analogue will have a length of at least 20 residues, preferably at least 40 residues, and most preferably at least 60 residues. H. pylori polypeptide fragments can be produced by techniques known in the art. The ability of a potential fragment to exhibit the biological activity of an H. pylori polypeptide can be assessed by methods known in the art described herein. Also included are H. pylori polypeptides containing residues that are not required for the biological activity of the peptide or those resulting from alternative mRNA splicing or alternative protein processing.

The term immunogenic component is a group, such as a H. pylori polypeptide, fragment or analog thereof, which can elicit a humoral and / or antibody immune response in a host alone or in combination with an adjuvant.

The term antigen component is a moiety, such as a H. pylori polypeptide, fragment or analog thereof, that is capable of binding to a specific antibody with sufficient affinity to form a detectable antigen-antibody complex.

The term transgene refers to a nucleic acid (encoding, for example, one or more polypeptides) that is partially or w

9 ’·’ · · · ·. '·. · '9

9999

Fully heterologous, i.e. foreign, to the transgenic animal or cell into which it is inserted or homologous to the endogenous gene of the transgenic animal or cell; into which it is inserted, but which is to be inserted or is inserted into the cellular genome in such a way that it changes the genome of the cell to which it is inserted (for example, it is inserted at a location different from the natural site of the gene or leads to insertion of the gene). The transgene may comprise one or more transcriptional regulatory sequences and any other nucleic acid, such as introns, that may be necessary for optimal expression of the selected nucleic acid that are bound to the selected nucleic acid and may contain a transcription enhancer.

The term transgenic cell as used herein refers to a cell containing the transgene.

The term transgenic animal as used herein refers to an animal whose one or more cells, and preferably all cells, contain a transgene. The transgene may be introduced into the cell directly or indirectly by insertion into a cell precursor, by any genetic manipulation, such as techniques for transforming competent cells by microinjection or recombinant virus infection. This molecule may be integrated into the chromosome, or it may be extrachromosomally replicating DNA.

The term antibody as used herein includes fragments thereof that are specifically reactive with H. pylori polypeptides.

As used herein, the term cell-specific promoter refers to a DNA sequence that serves as a promoter, i.e. regulates the expression of a selected DNA sequence that is operably linked to a promoter and that affects the expression of the selected sequence, DNA in specific

Also included are so-called leaky promoters that regulate the expression of selected DNA primarily in one tissue, but may also cause expression in other tissues.

Mis-expression refers to unnatural type / gene expression. It involves expression in unnatural amounts, i.e., over- or under-expression; expression that differs from natural expression at the stage or time at which the gene is expressed, for example, increased or decreased expression (as compared to natural expression) at a predetermined developmental stage or stage; expression that differs from natural expression in terms of reduced expression (as compared to natural expression) in a predetermined cell or tissue type; expression that differs from natural expression in terms of splice size, amino acid sequence, post-translational modifications, or biological activity of the expressed polypeptide; expression that differs from natural expression in terms of the effect of environmental or extracellular stimuli on gene expression, for example, increased or decreased expression (as compared to natural expression) in the presence of an increased or decreased stimulus.

The term host cell and other such terms referring to a microorganism or other higher eukaryotic cell line cultured as a monocellular entity means cells that may be recipients or are recipients of a recombinant vector or other transferred DNA and include progeny of the parent cell that has been transfected. It is known to those skilled in the art that the progeny of a single cell need not necessarily be completely identical in genomic or total DNA to the parent parent cell, due to deliberate or random mutations.

As used herein, the term control sequence refers to a nucleic acid having a base sequence that is recognized by the host organism and affects the expression of the encoded sequence to which it is encoded.

·· e

• 0 0 ·

0 000 0000 • t 00β0

0 0 0 00 τι — ΟΙ 0 0 ·

Ď 0 0 0

0 ·; 0 «00 0 0

00 ligated. The nature of such control sequences varies according to host organisms: in prokaryotic organisms, they include • such control sequences, typically a promoter, ribosome binding sites, terminators, and in some cases operators; in eukaryotic organisms, such control sequences include promoters, terminators, and, in some cases, enhancers. The term control sequence includes at least all of the components whose presence is required for expression and may also include other components whose presence is preferred, for example, a leader sequence.

As used herein, the term "operably linked" refers to a sequence attached or ligated to function as desired. For example, a control sequence is operably linked to a coding sequence by ligation such that expression of the coding sequence occurs under conditions compatible with the control sequence and the host cell.

Substance metabolism refers to any aspect of the expression, function, action or regulation of a substance. The metabolism of a substance includes modifications, for example, covalent or non-covalent modifications of the substance. The metabolism of a substance includes modifications, for example, covalent or non-covalent modifications, induced by the substance in other substances. Substance metabolism also includes changes in substance distribution. The metabolism of the substance also includes the changes induced by the substance in the distribution of other substances.

As used herein, the term sample refers to a biological sample such as tissue or fluid isolated from an individual (including but not limited to plasma, serum, cerebrospinal fluid, lymph, tears, saliva and tissue sections) or from cell culture components in vitro, as well as samples environment.

ty ¹ í mi.

Unless otherwise stated, conventional chemistry, molecular biology, microbiology, recombinant DNA, and immunology techniques known in the art are used in the practice of this invention. Such techniques are fully explained in the literature. See, for example, Sambrook, Fritsch and Maniatis, Molecular Cloning: Laboratory Manual, 2nd Edition, (, 1989); DON Cloning, Volumes I and II (D.N.

Glover eď. Oligonucleotide Synthesis (MJ Gait ed. 1984); Nucleic Acid Hybridization (BD Hames & SJtHiggins ed. 1984); series, Methods in Enzymology · (Academic Press, Inc.), especially volumes 154 ^j and 155 (Wu and Grossman, eds.) and PCR - A.Practical Approach (McPherson, Quirke and Taylor, eds., 1991).

I. Isolation of H. pylori nucleic acids and their use

The genomic sequence of H. pylori

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

To determine the genomic sequence of H. pylori, DNA was isolated from a H. pylori strain (ATCC # 55679; deposited by Genome Therapeutics Corporation, 100 Beaver Street, Waltham, MA 02154) and was mechanically cut by nebulization to a 2 kb median. After size fractionation using gel electrophoresis, the fragments were blunt-ended, ligated to adapter oligonucleotides, and cloned into each of 20 different pMPX vectors (Rice et al., Abstracts of Meeting of Genome Mapping and Sequencing, Cold Spring Harbor, NY, 5/11-5/15, 1994, p. 225) for the construction of a series of general subclone libraries.

DNA sequestration was performed using multiple sequencing procedures as described in Church et al., 1988, Science 240: 185; U.S. Pat. Nos. 4,942,124 and 5,149,625. DNA was extracted from culture sets and subjected to chemical or enzymatic sequencing. The sequencing reaction products 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 labeled oligonucleotides complementary to the stem sequences present in various general cloning vectors. In this way, a large number of sequences can be obtained from a single set of sequencing reactions. The cloning and sequencing procedures are described in more detail in the Examples.

Individual sequence readings obtained in this manner were performed using the FALCON ™ program (Church et al., 1994, Automated DNA Sequencing and Analysis, JC Venter, ed., Academic Press) and PHRAP (P. Green, Abstracts of DOE Human Genome Program Contractor). Grantee Workshop V, 1/1996, p. 175). The average length of the sequences was approximately 3-4 kb.

Many techniques are used to align the sequences to obtain a continuous sequence representing the entire H. pylori genome. Synthetic oligonucleotides are designed to be complementary to sequences at the ends of each partial sequence. These oligonucleotides can hybridize to H. pylori genomic DNA libraries in, for example, lambda phage vectors or plasmid vectors to identify clones that contain sequences corresponding to linker regions between individual partial sequences. . Such clones are then used to isolate template DNA and the same oligonucleotides are used in the polymerase chain reaction (PCR) to amplify the linker fragments whose nucleotide sequence is then determined.

H. pylori sequences were analyzed for the presence of open reading frames (ORFs) containing at least 180 nucleotides. Since the ORF analysis results are based on readings from the stop to the stop codon, these ORFs may not correspond to the ORFs of the native H. pylori polypeptides. These ORFs may contain start codons that determine the initiation of protein synthesis of the native H. pylori polypeptide. Such start codons in the ORFs disclosed herein can be identified by those skilled in the art, and the resulting ORF and the encoded H. pylori polypeptide are within the scope of the present invention. For example, a codon such as AUG or GUG (encoding methionine or valine) that is part of the protein synthesis initiation signal may be identified in the ORF and the ORF may be modified to correspond to the native H. pylori polypeptide. The putative coding regions were identified by evaluating the coding potential of such sequences using the GENEMARK ™ program (Borodovsky and McLinchch, 1993, Comp. Chem. 17: 123).

Other H. pylori nucleic acids

Nucleic acids of the present invention can be obtained directly from the DNA of the above H. pylori strain using polymerase chain reaction (PCR). See PCR - A Practical Approach (McPherson, Quirke and Tazlor ed., IRL Press, Oxford, UK, 1991) for a detailed description of PCR. High reliability PCR can be used to ensure true copies of DNA prior to expression. In addition, the authenticity of the amplified products can be verified by conventional sequencing techniques. Clones containing the desired sequences of the present invention can be obtained by screening libraries using PCR or hybridization of synthetic oligonucleotide probes to colony-forming library filters or plaques, as is known in the art. (see, for example, Sambrook et al., MolecularCloning: A. Laboratory Manual, 2nd Edition, (1989), Cold Spring Harbor Laboratory Press,

NY).

It is also possible to obtain nucleic acids encoding polypeptides-H. pylori from the cDNA library according to the protocol described herein. The cDNA encoding the H. pylori polypeptide can be obtained by isolating total mRNA from a suitable strain. A double stranded cDNA can then be prepared from total mRNA. Then, the cDNA can be inserted into a suitable plasmid or viral (e.g., bacteriophage) vector using any technique known in the art. Genes encoding H. pylori polypeptides can also be cloned using established polymerase chain reaction techniques according to the nucleotide sequences included in the present invention. The nucleic acids of the present invention may be DNA or RNA. Preferred nucleic acids of the present invention are listed in the Sequence Listing.

The nucleic acids of the present invention can also be synthesized chemically using standard techniques. Various techniques for chemical synthesis of polydeoxynucleotides are known, including solid phase synthesis, which, like peptide synthesis, is fully automated in commercially available DNA synthesizers (see, e.g., Itakura et al. US Patent No. 4598049; Caruthers et al. And Itakura US Patent Nos. 4401796 and 7373 071, which are incorporated herein by reference).

Nucleic acids isolated or synthesized according to the present invention are useful, for example, as probes,

primers, capture ligands, antisense genes as well as for the development of expression systems for the synthesis of proteins and peptides corresponding to such sequences. In the case of probes, primers, capture ligands, and antisense sequences, the nucleic acid is typically composed of all or part (about twenty or more nucleotides to provide specificity, as well as to create stable hybridization products) of the nucleic acids of the present invention contained in the sequence listing. These uses are described in more detail below.

Probes

Nucleic acids isolated or synthesized according to the sequences of the present invention listed in the Sequence Listing are useful as probes for the specific detection of H. pylori. According to the sequences of the present invention, sequences comprising twenty or more nucleotides are identified that allow the desired sensitivity and specificity for H. pylori and foreign nucleic acids that are likely to be identified during hybridization. More preferably, the sequence will contain at least twenty to thirty nucleotides to ensure stability of the probe hybridization product and the desired target molecule.

Sequences longer than 1000 nucleotides are difficult to synthesize, but can be produced by recombinant DNA techniques. Those skilled in the art will recognize that nucleic acids for use as probes may be labeled to facilitate detection of the hybridization product.

Nucleic acids isolated or synthesized according to the sequences of the present invention listed in the Sequence Listing are also useful as probes for the detection of homologous regions

(Especially homologous genes) of other Helicobacter species using the appropriately stringent hybridization conditions described herein.

Catch ligand

For use as a capture ligand, the nucleic acid described above as a probe can be readily attached to a support. Methods for attaching a nucleic acid to a carrier are well known. A nucleic acid having twenty or more nucleotides of the sequences of the present invention listed in the Sequence Listing can be used to separate H. pylori nucleic acid from the nucleic acid of other and other organisms. A nucleic acid having twenty or more nucleotides of the sequences of the present invention listed in the Sequence Listing can also be used to separate other Helicobacter species from other and other organisms. Preferably, the sequence will contain at least twenty nucleotides to ensure stability of the hybridization product formed by the probe and the desired target molecule. Sequences longer than 1000 nucleotides are difficult to synthesize, but can be produced by recombinant DNA techniques.

Primers

The nucleic acid isolated or synthesized according to the sequences described herein is useful as a primer for amplifying H. pylori nucleic acid. These nucleic acids can also be used to amplify nucleic acids of other Helicobacter species. According to polymerase chain reaction (PCR) techniques, 10-15 nucleotide nucleic acid sequences of the present invention contained in the sequence listing are useful together with suitable enzymes and reagents for producing copies of H. pylori nucleic acid. Preferably, the sequence will comprise at least twenty or more nucleotides to provide stability

ΦΦΦΦΦ a hybridization product consisting of a primer and a desired target molecule. Binding conditions of primers longer than 100 nucleotides are difficult to control to ensure specificity. High reliability PCR can be used to ensure true copies of DNA prior to expression. In addition, the amplified products can be verified by conventional sequencing techniques.

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

Antisense sequences

The nucleic acid or hybridizing nucleic acid derivative isolated or synthesized according to the sequences described herein is useful as an antisense sequence to prevent expression of H. pylori genes. These sequences are also useful as antisense sequences to prevent expression of genes from other Helicobacter species.

In one embodiment, the nucleic acid or derivative corresponding to H. pylori nucleic acid is inserted into a suitable carrier, such as a liposome or bacteriophage, for introduction into bacterial cells. For example, a nucleic acid of twenty or more nucleotides in length is capable of binding to a bacterial nucleic acid or a bacterial mediator RNA. Preferably, the antisense nucleic acid comprises 20 or more nucleotides to ensure the necessary stability of the hybridization product of non-naturally occurring nucleic acid and bacterial nucleic acid and / or bacterial mediator RNA. Nucleic acids longer than 1000 nucleotides are difficult to synthesize, but can be produced by recombinant DNA techniques. Methods for introducing antisense and listed 1980 nucleic acids into liposomes are known in the art, for example, in U.S. Pat. No. 4241046 issued December 23, 2002

Papahadjopoulos et al.

II. Expression of H. pylori nucleic acid

A nucleic acid isolated or synthesized according to the sequences described herein is useful for making polypeptides. The nucleic acid of the present invention listed in the sequence or fragments of said nucleic acid-encoding active portions of H. pylori polypeptides may be cloned into suitable vectors or used for nucleic acid isolation. The isolated nucleic acid is combined with suitable DNA binding sequences 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 in which the activity of the gene product determined by the gene or operon of interest can be specifically measured. Alternatively, the gene product can be produced in large quantities in an expressing strain and can be used as an antigen, an industrial reagent, for structural studies and the like. This expression can be performed in a mutant strain that lacks the activity of the test gene or in a strain that does not produce the same gene product. These include, without limitation, other Helicobacter strains, or other bacterial strains such as E. coli, Norcardia, Corynebacterium, Campylobacter, and Streptomyces.

In some cases, the expressing host will utilize the native Helicobacter promoter, while at other times it will be necessary to direct the expression of the gene by a promoter sequence derived from the expressing organism (e.g., the E. coli β-galactosidase promoter for expression in E. coli).

For expression of a gene product using a natural promoter

H. pylori can be used. The restriction fragment containing the gene of interest, together with its associated natural promoter element and regulatory sequences (identified using DNA sequence data) is cloned into a suitable recombinant, plasmid containing the origin of replication functional in the host organism and a suitable selectable gene. / marker. This can be accomplished by many techniques known in the art.

Most preferably, this is done by digesting the plasmid and the cloned fragment with the same restriction enzyme to form competitively termed ends which can then be ligated together. The recombinant plasmid is introduced into host organisms, for example, by electroporation, and cells containing the recombinant plasmid are identified by marker selection on the plasmid. Expression of the desired gene product is detected using an assay specific for that gene product.

In the case of a gene that requires a different promoter, the gene (coding sequence) is specifically excised and cloned into a suitable expression plasmid. This subcloning can be accomplished by a variety of techniques, but is best accomplished by PCR amplification of a specific fragment and ligation into an expression plasmid after treatment of the PCR product with a restriction enzyme or exonuclease to create appropriate cloning ends.

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

Expression in eukaryotic cells such as mammalian, insect cells or yeast can result in partial or complete glycosylation and / or. To form relevant inter- or intra-chain disulfide bonds of the produced recombinant peptide. Examples of vectors for yeast S. cerevisiae expression include pYepSec1 (Baldari et al, (1987) EMBO J. 6: 229 '- 234), pMFα (Kurjan and Herskowitz (1982). Cell 30: 933- 943), pJRY88 (Schultz et al., (1987) Gene 54: 113-123) and pZES2 (Invitrogen Corporation, San Diego, CA). Baculovirus vectors available for expression of proteins in cultured insect cells (SF9 cells) include the pAc series (Smith et al., (1983) Mol. Cell. Biol. 3: 2156-2.165) and the pVL series (Luclow VA and Summers, M. (1989)

Virology 170: 31-39). Usually, COS cells (Gluzman, Y. (1981) Cell 23: 175-182) are used with vectors such as pCDM 8 t

(Aruffo, A. and Seed, B. (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.

The vector DNA may be introduced into mammalian cells by conventional techniques such as calcium phosphate or calcium chloride precipitation, DEAE-dextran mediated transfection or electroporation. Preferred techniques for transforming host cells are disclosed in Sambrook et al. 20.00 Molecular Cloning:

A Laboratory Manual, 2nd Edition, (1989), Cold Spring Harbor Laboratory Press, NY) and other textbooks.

Expression in prokaryotes is most commonly performed in E. coli using either fusion or non-fusion inducible expression vectors. Fusion vectors usually add a number of NH ₂ terminal amino acids to the expressed gene. These NH ₂ terminal amino acids are often referred to as a reporter group. Such reporter groups usually serve two purposes: 1) increase the solubility of the target recombinant protein; and 2) assist in the purification of the target recombinant protein by acting as a ligand in affinity purification. Often in the fusion expression vectors, a proteolytic cleavage site is inserted at the junction of the reporter group and the target recombinant protein from the reporter group to allow separation of the target recombinant protein from the reporter group after purification of the fusion protein. Such enzymes, and their corresponding recognition sequences, include Factor Xa, thrombin, and enterokinase. Typical fusion expression vectors include pGEX (Amrad Corp., Melbourne, Australia), pMAL (New England Biolabs; Beverly, MA) and pRIT5 (Pharmacia, Piscataway,

NJ) which fuse glutahione-S-transferase, E maltose binding protein or protein A, respectively, to the target recombinant protein. A preferred reporter moiety is His (poles), which can be fused to the amino- or carboxy-terminus of the protein and which allow easy purification of the recombinant fusion protein by metal chelate chromatography.

Inducible non-fusion expression vectors include pTrc (Amann et al., (1988) Gene 69: 301-315) and pET11d (Studier et al., Gene

Expression Technology: Methods in Enzymology 185, Academic Press, San Dlego, California (1990) 60-89). While the expression of the target gene is based on transcription of the host RNA polymerase from the hybrid trp-lac promoter in pTrc, the expression of the target gene inserted into pET11d consists in transcription from the T7 gn10-lac 0 fusion promoter which is mediated by coexpressed viral RNA polymerase . This viral polymerase is supplied by the host strain BL21 (DE3) or HMS174 (DE3) contained herein by the labda prophage carrying T7 gnl under 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 suitable conditions allowing expression of the polypeptide. The polypeptide may be secreted

• ·· • · 9 • · • · * ·· • · ·· ·· • · · · • · • · • · · • · · · · · • · • • · • · • · · · ··· • · • • 9 9

and isolated from a mixture of cells and media containing the peptide.

Alternatively, the polypeptide may be retained in the cytoplasm, and cells may be harvested, lysed, and the protein isolated. The cell culture comprises host cells, medium and other "by-products". Suitable cell culture media are known in the art. The polypeptides of the present invention can be isolated from cell culture medium, host cells, or both using techniques known in the art for protein purification, including ion exchange chromatography, gel filtration chromatography, ultrafiltration, electrophoresis, and immunoaffinity purification using antibodies specific for such polypeptides. Further, in many situations, the polypeptides can be produced by chemical cleavage of the native protein (e.g., trypsin digestion), and the cleavage products can then be purified by standard techniques.

In the case of membrane-bound proteins, these proteins can be isolated from host cells by contacting the membrane-associated protein fraction with a solubilized complex detergent in which the membrane-associated protein is no longer fully immersed in the membrane fraction and is solubilized to at least the extent that allows it chromatographic isolation from the membrane fraction. Several different criteria are used to select a detergent suitable for solubilizing these complexes. For example, one criterion is the ability of the detergent to solubilize the H. pylori protein in the membrane fraction with minimal denaturation of the membrane associated protein to allow restoration of the activity or function of the membrane associated protein upon reconstitution of the protein. Another criterion for detergent selection is the critical micelle concentration (CMC) of the detergent, wherein the detergent of choice preferably has a high CMC value to allow easy removal after reconstitution. The third criterion is the hydrophobic nature of the detergent. Usually, proteins are associated

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With membranes very hydrophobic, detergents that are also hydrophobic, such as triton series detergents, will be useful for solubilizing hydrophobic proteins. Another important property of detergents may be the ability of detergents to remove H. pylori protein with minimal protein-protein interaction, which facilitates further purification. The fifth criterion for detergent selection is detergent charge. For example, if an ion exchange resin is used in the purification process, the detergent should be a non-charged detergent. Chromatographic techniques that can be used in the final purification are known in the art and include hydrophobic interactions, lectin affinity, ion exchangers, affinity for dyes, and immunoaffinity.

One strategy to maximize expression of recombinant H. pylori peptide in E. coli is to express the protein in a host bacterium with a disrupted capacity for proteolytic cleavage of the recombinant protein (Gottesman, S., Gene Expression Technology: Methods in Enzymology 185, Academic Press, San Dlego, California. (1990) 119-128). Another strategy is to alter the nucleic acid encoding the H. pylori peptide to be inserted into the expression vector such that the individual codons for each amino acid will be those codons that are preferentially used for high-expressed E. coli proteins (Wada et al. , (1992) Nuc. Acids Res. 20: 2111-2118). Such alteration of nucleic acids of the present invention can be accomplished by standard DNA synthesis techniques.

The nucleic acids of the present invention can also be synthesized chemically using standard techniques. Various methods for the chemical synthesis of polydeoxynucleotides are known, including solid phase synthesis, which, like peptide synthesis, is fully automated in commercially available DNA synthesizers (see, e.g., Itakura et al. U.S. Patent No. 4598049; Caruthers et al.

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9 9 9 al., U.S. Pat. U.S. Patent No. 4,480,666; and Itakura U.S. Pat. Nos. 4401796 and 7373071, which are incorporated herein by reference).

III. H. pylori polypeptides

The invention includes isolated H. pylori polypeptides encoded by the disclosed H. pylori genomic sequences, including the polypeptides of the present invention listed in the Sequence Listing. The polypeptides of the present invention preferably have a length of at least 5 amino acid residues. _Use: DNA sequences disclosed herein may be by well known techniques, the deduced amino acid sequence of the polypeptides of the present ^ invention. It should be understood that the entire nucleic acid / coding sequence of H. pylori polypeptide can be isolated and identified based on an ORF that encodes only a fragment of the corresponding protein-coding region. This can be achieved, for example, using an isolated nucleic acid encoding the ORF, or fragments thereof, to initiate a polymerase chain reaction with H. pylori genomic DNA as a template; followed by sequencing of the amplified product.

The polypeptides of the present invention can be isolated from natural 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 they have been introduced and in which they have been expressed. H. pylori nucleic acid. In addition, the polypeptides may be part of recombinant fusion proteins.

The H. pylori polypeptides of the present invention can be chemically synthesized using automated procedures, which are incorporated herein by reference.

IV. Identification of nucleic acids encoding vaccine components and targets for agents active against H. pylori

The disclosed H. pylori genomic sequences contain segments that direct the synthesis of ribonucleic acid and polypeptides, as well as elements that recognize the origin of replication, promoters, other types of regulatory sequences, and intergenic nucleic acids. The invention includes nucleic acids encoding immunogenic vaccine components and targets for agents effective against H. pylori. The identification of said immunogenic components involved in determining the function of the disclosed sequences may be accomplished by various techniques. Non-limiting examples of such techniques are briefly described below.

Homology to Known Sequences: Computer comparison of the described H. pylori sequences with previously described sequences in publicly available databases is useful for identifying functional H. pylori nucleic acids and polypeptides. It should be understood that sequences encoding a protein, for example, can be compared as a whole, and that a high degree of sequence homology between two proteins (e.g.,> 80-90%) at the amino acid level indicates that the two proteins also have some degree of functional homology, such as homology between enzymes involved in metabolism, DNA synthesis, or cell wall synthesis, and homology between proteins involved in transport, cell division, etc. In addition, many structural features of individual protein classes have been identified and correlate with specific conventional sequences, such as nucleotide, DNA, metal ion and other small molecule binding domains; covalent modification sites such as phosphorylation, acylation and the like; protein: protein interaction sites, etc. These conventional sequences can be quite short and can only represent a fraction of the entire protein-coding sequence. The identification of such features in the H. pylori sequence is therefore useful to determine the function of the encoded protein and to identify targets for antibacterial drugs.

Of particular interest to the present invention are those features common to secretions. transmembrane and surface proteins, including secretory signal peptides and hydrophobic transmembrane domains. H. pylori proteins likely containing signal sequences and / or transmembrane domains are useful as immunogenic components of vaccines.

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

Strain-specific sequences: Because of the evolutionary relationship between different H. pylori strains, it is believed that the described H. pylori sequences are useful for identifying and distinguishing known and novel H. pylori strains. Other H. pylori strains are expected to have at least 70% sequence homology with the sequences of the present invention. Systematic and routine analysis of DNA sequences obtained from samples containing H. pylori strains and comparison with sequences of the present invention will allow identification of sequences that can be used to distinguish strains, as well as identification of those sequences that are common to all H. pylori strains. In one embodiment, the invention comprises nucleic acids, including probes, and peptides and polypeptide sequences that distinguish individual strains of H. pylori. Strain-specific components can also be identified functionally by their ability to elicit antibodies or react with

antibodies that selectively recognize one or more H. pylori strains. In another embodiment, the invention comprises nucleic acids, including probes, and peptides and polypeptide sequences that are common to all H. pylori strains but which are not present in other bacterial species.

Specific Example: Determination of potential protein antigens for antibody and vaccine development

Selection of potential protein antigens for vaccine development can be made using nucleic acids encoding H. pylori polypeptides. First, the ORF can be analyzed for homology with other known secreted α-membrane proteins and can be analyzed using the discriminant analysis described by Klein et al. (Klein, P., Kanehsia, M., and DeLisi, C.

(1985) Biochimica et Biophysica Acta 815: 468-477) for the determination of secreted and membrane proteins.

Homology screening can be performed using the BLAST algorithm contained in the Wisconsin Sequence Analysis Package (Genetics Computer Group, University Research Park, 575 Science Drive, Madison, WI 53711) to compare each putative amino acid sequence of the ORF with all of the presently disclosed ORF sequences. GenBank, SWISS-PROT and PIR databases. BLAST looks for local ORF assignment to sequences in databases and describes probability early that determines the probability of finding that sequence in the database. ORFs with significant homology (for example, the probability that the homology is random, less than 1 x 10 ⁶ ) with membrane or secreted proteins represent protein antigens for vaccine development. The possible function of H. pylori genes can be determined based on homology with genes cloned in other organisms.

• · · · · · · · • · • · • ·

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Discriminant analysis (Klein et al., Supra) can be used to determine the amino acid sequence of an ORF. This algorithm utilizes the intrinsic information contained in the amino acid sequence and compares it with information obtained from the properties of known membrane and secreted proteins. This comparison determines which protein will be secreted, associated with the membrane or deposited in the cytoplasm. The ORF amino acid sequences identified as being secreted or associated with the membrane are potential protein antigens for vaccine development.

and

The outer membrane membrane proteins are probably the best antigens to elicit, a protective immune response against H. pylori. To determine these outer membrane proteins, an amphipathic β-sheet region at the C-terminus may be used. This region, which has been detected in a large number of external membrane proteins in Gram negative bacteria, is often characterized by hydrophobic residues (Phe or Tyr) that are grouped at different positions in the C-terminus region (For example, see Fig. 5, block F; 7, block E). Importantly, these sequences were not detected in the C-terminus of the periplasmic proteins, allowing for a preliminary differentiation of these classes of proteins based on the primary sequence. This phenomenon is described by Struyve et al. (J. Mol. Biol. 218: 141-148, 1991).

Also shown in Figure 5 are additional amino acid sequence motifs found in many of the outer membrane proteins of H. pylori. The amino acid sequence alignment in Figure 5 shows parts of the sequence of the five H. pylori proteins (in a single letter amino acid code) identified by the amino acid sequence identification number and described from N-terminal to C-terminal, from left to right. There are five or six different blocks (designated A to E or F) of similar amino acid residues including various hydrophobic residues (Phe or Tyr; F or Y in a single letter code).

For amino acid residues), which are often found at positions near the C-terminus of the outer membrane proteins. The presence of several of the same motifs clearly determines the similarity of members of this family of proteins.

A further amino acid alignment for the four outer membrane proteins isolated from H. pylori is shown in Figure 6.

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

Those skilled in the art will appreciate that these test motif sequences are highly significant and determine the similarity in this family of proteins.

It rarely happens that it is impossible to distinguish between multiple possible nucleotides at a given position in a nucleic acid sequence. In these cases, ambiguous results are indicated by the following letters:

• · · · · · · ·

The official IUPAC-IUB- one letter code fits

Code Description of the base G Guanin AND Adenin T Thymidine C Cytosine R ------- Purin (AND or G) Y Pyrimidine (C or T or U) M Amino (AND or C) TO Ketone (G or T)

WITH Strong interaction (C or G) W Weak interaction (AND or T) H No-G (AND or C or T) (B) No-A (C or G or T) IN No-T (No-U) í 7 \ or / 1 IN, or G) D No-C (AND or G or T) N Any (AND or C or G or T)

The amino acid of the present invention translated from the ambiguous nucleic acid sequence from the ambiguous codon is designated X. In all cases, the possible amino acid residues are at a position apparent from the nucleic acid sequence determination, using the standard genetic code.

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

Depending on the H. pylori gene products of the present invention listed in the Sequence Listing, one skilled in the art may alter the described structure (H. pylori genes) by, for example,

Test fragments or analogs and test the activity of newly formed structures. Examples of techniques known in the art which can be used to produce and test fragments and analogs are set forth below. These techniques, or analogous techniques, can be used to produce polypeptide libraries, for example, random polypeptide libraries or libraries of fragments or analogs of cellular proteins, and screen for binding to H. pylori polypeptides. Such assays are useful for identifying H inhibitors. pylori.

Production of fragments

Protein fragments can be produced in various ways, for example, recombinantly, by proteolytic digestion, or by chemical synthesis. Internal or terminal fragments of a polypeptide can be produced by removing one or more nucleotides from one end (for the terminal fragment) or from both ends (for the internal fragment) of the nucleic acid that encodes the polypeptide. Upon expression of the mutated DNA, a polypeptide fragment is produced. Digestion using end-processing endonucleases can thus generate DNAs that encode an array of fragments. DNAs that encode protein fragments can also be generated by random digestion, restriction digestion, or a combination of the above techniques.

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

Alteration of Nucleic Acids and Polypeptides: Random Methods • 0000

0000 • 0 0

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Variants of the amino acid sequence of the protein may be prepared by random mutagenesis of a DNA that encodes a protein or a particular domain or region of a protein. Useful techniques include PCR-mutagenesis and saturation mutagenesis. A library of random amino acid sequence variants can also be generated using synthesis, a set of degenerate oligonucleotide sequences. (Techniques for protein screening in variant libraries are listed elsewhere herein).

(A) PCR mutagenesis

In PCR mutagenesis, Taq polymerase with reduced reliability is used to insert random mutations into a cloned DNA fragment (Leung et al., 1989, Technique 1: 11-15). The DNA region to be mutagenized is amplified using a polymerase chain reaction (PCR) under conditions that reduce the reliability of Taq DNA polymerase synthesis, for example using a dGTP / dATP ratio of five and adding Mn ² * to the PCR reaction mixture. . The sets of amplified DNA fragments are inserted into suitable cloning vectors to generate random mutant libraries.

(B) Saturation mutagenesis

Saturation mutagenesis allows rapid insertion of a large number of single base substitutions into cloned DNA fragments (Mayers et al., 1985, Science 229: 242). This technique involves the generation of mutations, for example by chemical processing or irradiation of single-stranded DNA in vitro, and the synthesis of complementary DNA strands. The frequency of mutations can be influenced by a change in processing intensity and virtually all possible base substitutions can be obtained. Since this technique does not include genetic selection for the mutated fragments, both neutral and function-altering substitutions are obtained. Distribution • i 't *

9 9 point mutations are not affected by an error in the sense of conserved sequence elements.

(C) degenerate oligonucleotides

A library of homologues can also be generated using degenerate oligonucleotide sequences. Chemical synthesis of degenerate sequences can be performed on an automated DNA synthesizer, and the synthetic gene is then ligated into a suitable expression vector. The synthesis of degenerate oligonucleotides is known in the art (see, for example, Narang, S.A. (1983) Tetrahedron 39: 3; Itakura et al., (1981) Recombinant DNA, Proc 3rd Cleveland)

Sympos. Macromolecules, ed. A.G. Walton, Amsterdam: Elsevier pp. 273-289; Itakura et al., (1984) Annu. Roar. Biochem. 53: 323;

Itakura et al., (1984) Science 198: 1056; Ike et al., (1983)

Nucleic Acids Res. 11: 477. Such techniques can be used in the direct development of other proteins (see, for example, Scott et al., (1990) Science 249: 386- 390; Roberts et al., (1992) PNAS 89: 2429 2433; Devlin et al. (1990) Science 249: 404-406; Cwirla et al., (1990) PNAS 87: 6378-6382; as well as US Patent Nos. 5,223,409, 5,198,346, and 5,968,615).

Alteration of nucleic acids and polypeptides: Methods for directed mutagenesis

Non-random or directed mutagenesis techniques can be used to produce specific sequences or mutations in specific regions. These techniques can be used to make variants that contain, for example, deletions, insertions, or substitutions of residues of a known amino acid sequence of a protein. The mutation sites may be modified singly or in series, for example (1) by first conserved amino acid substitution and then more radically, depending on the result achieved, (2) deletion of the target residue, or (3) or a combination of these modifications.

(A) .Alanine screening mutagenesis

Alanine screening mutagenesis is a useful technique for identifying certain residues or regions of a desired protein that are preferred sites for mutagenesis (Cunningham and Wells,

Science 244: 1081 (1085, 1989). In alanine screening, a residue or group of residues (e.g., charged residues such as Arg, Asp, His, Lys, and Glu) is identified and is replaced by a neutral or negative charge amino acid (preferably alanine or polyalanine). Amino acid substitution can affect the interaction of amino acids with the surrounding aqueous environment in or outside the cell. Those domains that exhibit functional sensitivity to substitution are then engineered by inserting additional or other variants at the site of substitution. Therefore, although the site for insertion of the amino acid sequence variation is predetermined, the nature of the mutation itself may not be predetermined. For example, to optimize a mutation at a given site, alanine screening or random mutagenesis can be performed at the target codon or region, and the expressed desired variants of the protein subunit are screened for the optimal combination of the desired activity.

(B) Oligonucleotide-mediated mutagenesis

Oligonucleotide-mediated mutagenesis is a useful technique for preparing substitution, insertion, and deletion variants of DNA, see, e.g., Adelman et al., (DNA 2: 183, 1983). Briefly, the DNA of interest is altered by hybridizing the oligonucleotide encoding the mutation to a DNA template, wherein the template is a single-stranded form of a plasmid or bacteriophage containing an unaltered or natural DNA sequence of the protein of interest. After hybridization, the entire second into which the DNA.polymerase for synthesis of the complementary template strand is used, the oligonucleotide primer and which will thus encode the selected DNA alteration for the desired protein. Typically, oligonucleotides of at least 25 nucleotides in length are used. The optimal oligonucleotide will contain 12 to 15 nucleotides that are completely complementary to the template on either side of the nucleotide encoding the mutation. This ensures that the oligonucleotide will properly hybridize to the single-stranded DNA molecule. Oligonucleotides can be readily synthesized using techniques known in the art, such as that described in Crea et al., (Proc. Natl. Acad. Sci. USA 75: 5765 (1978)).

(C) Cassette mutagenesis

Another technique for preparing variants, cassette mutagenesis, is based on the technique described by Wells et al., (Gene 34: 315 (1985)) The starting material is a plasmid (or other vector) that contains DNA for the subunit of the protein to be mutated. .

The codons in the DNA for the protein subunit to be mutated are identified. A unique restriction endonuclease site must exist on each side of the identified mutation site. If such a restriction site does not exist, it must be generated using the above-mentioned oligonucleotide-mediated mutagenesis technique and inserted into a suitable DNA position for the protein subunit. After insertion of the restriction site into the plasmid, the plasmid is cut and linearized at these sites.

A double stranded oligonucleotide encoding the DNA sequence between the restriction sites but containing the desired mutation is synthesized using conventional techniques. The two strands are synthesized separately and then hybridized together using conventional techniques. This double-stranded oligonucleotide is referred to as a cassette. This cassette is designed to have 5 'and 3' ends that are compatible with the ends of the uninearized, plasmid, so. it can be directly ligated into a plasmid. Such a plasmid then contains the desired mutated DNA sequence for the protein subunit.

(D) Combinatorial mutagenesis

Combinatorial mutagenesis can also be used to generate mutants (Ladner et al., WO 88/06630). In this technique, the amino acid sequences for a group of homologs or other related proteins are aligned, preferably to achieve the highest homology. All amino acids that are in a given position of aligned sequences can be selected to generate a degenerate set of combinatorial sequences. The general variant library is composed of combinatorial mutagenesis at the nucleic acid level and is encoded by the general gene library. For example, a mixture of synthetic oligonucleotides may be enzymatically ligated into gene sequences such that a degenerate set of potential sequences is expressible as individual peptides, or alternatively, as a set of larger fusion proteins comprising a set of degenerate sequences.

Further modifications of H. pylori nucleic acids and polypeptides

It is possible to modify the structure of the H. pylori polypeptide to provide greater solubility, higher stability (e.g., ex vivo viability and resistance to proteolytic degradation in vivo). A modified H. pylori protein or peptide may be made in which the amino acid sequence has been altered, for example, by amino acid substitution, deletion, or addition as described herein.

The H. pylori peptide may also be modified by substitution of cysteine residues, preferably alanine, serine, threonine,

leucine or gluconic acid to minimize the disulfide bond dimerization. Further, the amino acid side chains of the protein fragments of the present invention may be chemically modified. Another modification is the cyclization of the peptide. .

To increase stability and / or reactivity, the H. pylori polypeptide may be modified to incorporate one or more polymorphisms in the amino acid sequence of the protein resulting from natural allelic variation. In addition, D-amino acids, non-naturally occurring amino acids, or non-amino acid analogs can be added or substituted to provide a modified protein of the present invention. Further, the H. pylori polypeptide may be modified using polyethylene glycol (PEG) according to the technique described by A. Sehon et al. (Wie et al., Supra) to produce a PEG conjugated protein. In addition, PEG may be added during protein synthesis. Other modifications of H. pylori proteins include reduction / alkylation (Tarr., Methods of Protein Microcharacterization, J.E. Silver ed., Humana Press, Clifton NJ, 155-194 (1986)); acylation (Tarr, supra); chemical binding to a suitable carrier (Mishell and Shiigi, ed., Selected Methods in Cellular Immunology, WH Freeman, San Francisco, CA (1980), US Patent 4939239; or gentle formalin treatment (Marsh (1971) Int. Arch. of Allergy and Appl. Immunol. 41: 199-215).

To facilitate purification and to potentially increase the solubility of the H. pylori protein or peptide, it is possible to add an amino acid fusion group to the peptide backbone. For example, hexa-histidine may be added to the protein for purification by immobilized metal ion affinity chromatography (Hochuli, E. et al., (1988)

Bio / Technology 6: 1321-1325). Further, to facilitate the isolation of peptides without undesired sequences, there may be a specific site for

Even endoprotease digestion was inserted between the fusion group and peptide sequences.

To facilitate proper processing of H. pylori antigens, a conventional protease-sensitive site may be engineered between two regions that each contain at least one epitope, using recombinants. or / synthetic methods. For example, charged amino acid pairs, such as KK or RR, may be inserted between regions of a protein or fragment in a protein.

The course of its recombinant construction. The resulting peptide may be sensitive to cleavage by cathepsin and / or trypsin-like enzymes that will form portions of the protein containing i / one or more epitopes. In addition, charged amino acid residues may also increase the solubility of the peptide.

Primary methods for screening polypeptides and analogs. '. on ·

Various techniques are known in the art for screening the generated mutant gene products. Techniques for screening gene libraries often include cloning the gene library into replicable expression vectors, transforming suitable cells with the resulting vector library, and expressing genes under conditions where detection of the desired activity, such as binding to an H. pylori polypeptide or interacting protein, facilitates relatively easy isolation of the vector encoding the gene whose product has been detected. Each technique described below is suitable for high throughput analysis to investigate a large number of generated sequences, for example generated by random mutagenesis techniques.

(A) Two hybrid system

Two hybrid assays, such as the system described above (for other screening techniques described herein), can be used

-AND

for the identification of polypeptides, e.g. fragments or analogs of the native H. pylori polypeptide, e.g., cellular proteins or randomly generated polypeptides that bind to the H. pylori protein. (The H. pylori domain is used as a capture protein and the variant libraries are expressed as fusion proteins to be captured). Similarly, a two-hybrid assay (as described herein for other screening techniques) can be used to screen for polypeptides that bind to a H. pylori polypeptide.

(B) Imaging libraries

In one embodiment, the screening tests are. potential peptides displayed on the surface of cells or viral particles, and the ability of individual cells or viral particles to bind to a suitable receptor protein via the displayed product in a panel assay is detected. For example, a gene library may be cloned into a bacterial cell surface membrane protein and fusion protein can be detected by paneling (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 manner, a detectably labeled ligand can be used to assess potential functional homologues of a peptide. Fluorescently labeled ligands, for example, receptors, can be used to detect homologues that retain ligand binding activity. The use of fluorescently labeled ligands allows the cells to be visualized and separated by fluorescence microscopy, or, if cell morphology so permits, to separate them in a fluorescent activated cell sorter.

The gene library can be expressed as a fusion protein on the surface of viral particles. For example, in a filamentous phage system, a foreign peptide sequence may be expressed on the surface of an infectious phage, which has two significant advantages. First, since these phages can be applied to affinity matrices at concentrations greater than 10 ^{x 3} phage per ml, a large number of phages can be screened at one time. Second, because each infectious phage displays the gene product on its surface, so long as a particular phage is obtained from the affinity matrix; in low yield, it can be amplified in the "second round of infection." A group of nearly identical E. coli filamentous phages M13, fd., And fl is most commonly used in phage display libraries. Both the phage gl11 and gVIII coat proteins can be used to generate fusion proteins without disrupting the final structure of the viral particle. Foreign epitopes can be expressed at the NH ₂ -terminus diligence and phage bearing such epitopes may be recovered from a large excess of phage without these epitopes "(Ladner et al. PCT Publication No. WO 90/02909; Garrard et al. PCT application WO 92 / Marks et al., (1992) J. Biol Chem 267:

16007-16010; Griffiths et al., (1993) EMB0.J 12: 725-734;

Clackson et al., (1991) Nature 352: 624-628; and Barbas et al., (1992) PNAS 89: 4457-4461).

A common approach utilizes the E. coli maltose receptor (outer membrane protein, LamB) as a peptide fusion partner (Charbit et al., (1986) EMBO J. 5: 3029-3037). Oligonucleotides were inserted into a plasmid encoding the LamB gene to produce peptides fused to one of the extracellular loops of the protein. These peptides are accessible for binding to ligands, for example antibodies, and can elicit an immune response when cells are administered to animals. Other cell surface proteins, such as OmpA (Schorr et al., (1991) Vaccines 91, 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 the large surface structures of bacteria, can serve as carriers for peptide imaging.

Peptides can be fused to sawdust, a protein that polymerizes to form the pilus-a channel for interbacterial genetic exchange.

• 0 0 *>

information (Thiry et al., (1989) Appl. Environ. Microbiol. 55: 984)

- -993). Given his role. In interaction with other cells, pilus is a preferred carrier for the presentation of peptides in extracellular environments. Another large structure used to represent the peptide is the flagellar organ. Fusion of the peptide to the flagellin protein subunit allows the display of many copies of the peptide at high density on a host cell (Kuwajima et al., (1988) Bio / Tech 6: 1080-1083). Surface proteins of other bacterial species can also serve as peptide fusion partners. Examples include Staphylococcus protein A and Neisseria outer membrane IgA protease (Hansson et al., (1992) J.

Bacteriol. 174: 4239-4245 and Klauser et al., (1990) EMBO J.

9: 1991-1999).

In the filamentous phage systems and in the LamB system mentioned above, the physical binding between the peptide and its coding DNA is such that the DNA is contained in a particle (cell or phage) having the peptide on its surface. By trapping the peptide, the particles and the DNA contained therein are captured. An alternative scheme utilizes the DNA-binding protein Laci to create a bond between the peptide and DNA (Culi et al., (1992) PNAS USA 89: 1865-1869).

This system utilizes a plasmid containing the LacI gene with an oligonucleotide cloning site at its 3'-end. Under controlled induction by arabinose, the Laci-peptide fusion protein is produced. This fusion protein retains its natural ability to bind to a short DNA sequence known as the LacO operator (LacO). By installing two copies of LacO in an expression plasmid, the Lac-peptide fusion product tightly binds to the plasmid that encodes it. Since the plasmid in each cell contains only a single oligonucleotide sequence and each cell expresses only a single peptide sequence, the peptide is specifically and stably associated with the DNA sequence that directs its synthesis. Library cells are gently lysed and pepti-DNA complexes are · ·· ’···» ··· • ·. Exposed to a matrix containing an immobilized receptor to obtain complexes containing the active peptides. The associated plasmid DNA is then reintroduced into the cells for amplification and / or DNA sequencing is performed to determine the identity of the peptide / ligands. As an example of practical use of this method, a large random library of dodecapeptides was generated and a selection was made on a monoclonal antibody against the opioid peptide · dynorphin B.

A cohort of peptides was obtained that were all related in a consensus sequence corresponding to six residues of dynorphin B (Culi et al., (1992) Proc. Natl. Acad. Sci. USA 89:, 1869).

This scheme, sometimes referred to as peptides-on-plasmids, differs from phage display methods at two significant points.

First, the peptides are attached to the C-terminus of the fusion protein, resulting in the display of library elements as peptides having a free carboxy terminus. Both filamentous phage coat proteins, pIII and pVIH, are anchored in phage at their C-termini, and bound peptides are located on free N-terminal domains. In some cases, the phage displayed peptides are present in the amino-terminus of the fusion protein (Cwirla et al., (1990) Proc.

Nati. Acad. Sci. USA 87: 6387-6382). The second difference is a set of biological errors affecting the population of peptides currently present in libraries. The attractive fusion molecules are restricted to the cytoplasm of the host cells. Phage coat fusion proteins are transient in the cytoplasm during translation, but are rapidly secreted across the inner membrane into the periplasmic compartment, remaining anchored in the membrane through their C-terminal hydrophobic domains, with the N-terminus containing peptides extending into the periplasm, waiting for inclusion phage particles. Peptides in the Lacs and phage libraries may vary significantly due to exposure to various proteolytic activities. Phage coat proteins require transport across the inner membrane and signal peptidase processing prior to W9.0.99999.

Some peptides are disrupted by this treatment and are not representative of libraries (Gallop et al., (1994) J. Med. Chem. 37 (9): 1233-1251). These errors do not occur in Laci. imaging system.

The number of small peptides available in recombinant random libraries is considerable. Libraries containing ΙΟ ⁷ - 10 ⁹ independent clones are commonly prepared. Libraries containing up to 10 ¹¹ recombinants have been generated, but this size approaches the practical limit for clone libraries. This size limitation - libraries; consists in transforming DNA containing randomized segments into host bacterial cells. To overcome this limitation, an in vitro system based on imaging of nascent peptides in polysomal complexes was developed. This imaging library technique can produce libraries 3-6 orders larger than currently available phage / phagemid or plasmid libraries. In addition, the construction of libraries, peptide expression and screening is carried out completely without the participation of cells.

In one application of this technique (Gallop et al., (1994) J. Med.

Chem. 37 (9): 1233-1251), a molecular library of DNA encoding 10 ¹² decapeptides was constructed and the library was expressed in the S30 in vitro bound E. coli transcription / translation system. The conditions were selected such that the ribosomes were unblocked from the mRNA, causing the accumulation of a significant portion of the RNA in the polysomes and resulting in complexes containing nascent peptides still binding to their coding RNA. These polysomes are large enough for affinity purification at immobilized receptors using the same method used to screen conventional recombinant peptide display libraries. RNA from the bound complexes is recovered, converted to cDNA, and amplified by PCR to obtain a template for the next round of synthesis and screening.

Polysome imaging library can be associated with phage ····

imaging system. After several rounds of screening, cDNA from an enriched set of polysomes is cloned into a phagemid vector. This vector serves both as an expression vector for the peptide that displays the peptides fused to the envelope proteins and as a DNA sequencing vector to identify the peptide. When expressing polysome-derived peptides on phage, it is possible either to continue the affinity selection procedure in this format, or to test peptides on individual clones for binding activity in a phage ELISA assay, or to test peptides for binding specificity in complete phage ELISA assay (Barret et al., (1992) Anal. Biochem. 204: 357-364), to identify active peptide sequences on DNA sequences produced by a phagemid host.

Secondary investigation of polypeptides and analogues

The high performance assays described above may be followed by secondary screening to identify other biological activities that allow, for example, to distinguish agonists from antagonists. The type of secondary examination used will depend on the desired activity to be tested. For example, an assay can be developed in which the ability to inhibit the interaction between a protein of interest and its respective ligand can be used to identify antagonists from a group of peptide fragments isolated in one of the primary screening assays described above.

Methods for generating fragments and analogs and testing them for activity are known in the art. Once the essential sequence of interest has been identified, analogs and fragments can be readily obtained by those skilled in the art.

Peptide mimetics of H. pylori polypeptides «• φ φ φ φ φ φ φ φ φ

The invention also encompasses the reduction of protein-binding domains of H. pylori polypeptides by the production of mimetics, for example peptide or non-peptide agents. Peptide mimetics are capable of disrupting the binding of polypeptides to its ligand, for example, in the case of H. pylori polypeptides, its binding to a natural ligand. Critical residues of a particular H. pylori polypeptide that are involved in the molecular recognition of polypeptides can be identified and can be used to produce H. pylori-derived peptidomimetics that competitively or non-competitively inhibit binding of H. pylori polypeptides to the interacting polypeptide (see, e.g. EP-412462A and EP-B31080A).

For example, peptidomimetic compounds (for example, diazepine or isoquinoline derivatives) may be made to map the amino acid residues of a particular H. pylori polypeptide involved in binding to the interacting polypeptide of the screening mutagenesis, which obscure these residues when bound to the interacting polypeptide and thereby inhibit the binding of H. pylori polypeptides. to the interacting polypeptide and thus may interfere with the function of the H. pylori polypeptides. For example, non-hydrolyzable peptide analogs of such residues can be made using benzodiazepine (for example, see Freidinger et al., In Peptides: Chemistry and Biology, GR Marshall ed., ESCOM Publisher: Leiden, Netherlands, 1988), azepine (see, for example, Huffman et al. , in Peptides: Chemistry and Biology, GR Marshall ed., ESCOM Publisher: Leiden, Netherlands, 1988), substituted T-lactam rings (Garvey et al., in Peptides: Chemistry and Biology, GR Marshall ed., ESCOM Publisher: Leiden, Netherlands, 1988), keto-methylene pseudopeptides (Ewenson et al., (1986)

J. Med. Chem. 29: 295; and Ewenson et al., in Peptides: Structure and Function (Proceedings of the 9th American Peptide Symposium), Pierce Chemical Co., Rockland, IL, 1985, β-ordered dipeptide nuclei (Nagai et al., (1985) Tetrahedron Lett. 26 :

J. Chem. Soc.-Perkin. Trance. 1: 1231)

(Gordon et al., (1985) Biochem. Eiophys. Res.).

and Dann et al.,. . (1986) Biochem. Biophys. Res.

• 9 • 9

9 9 ·

647; and Sato et al and Commun β-aminoalcohols. .126: 419; Comm. 134: 71).

VI. Vaccines for nucleic acids and polypeptides

H. pylori

The present invention also relates to vaccine compositions and formulations (terms are interchangeable) for protecting against / against H. pylori infection or for treating H. pylori infection. As used herein, the treatment of H. pylori infection refers to the therapeutic treatment of an existing or advanced H. pylori infection. The terms protection against H. pylori infection or prophylactic treatment refers to the use of a vaccine against H. pylori to reduce the risk or prevent infection in a subject at risk of H. pylori infection. In one embodiment, the vaccine composition comprises one or more immunogenic components, such as a surface protein, H. pylori, or portions thereof, and a pharmaceutically acceptable carrier. For example, in one embodiment, the vaccine compositions of the present invention comprise at least one or a combination of H. pylori polypeptides or fragments thereof from the same or different H. pylori antigens. H. pylori nucleic acid and polypeptides for use in the vaccine compositions of the present invention include nucleic acids and polypeptides of the sequence listing, preferably those of H. pylori which encode surface proteins and surface proteins or fragments thereof. For example, the preferred H. pylori nucleic acid and polypeptide for use in the vaccine composition of the present invention is selected from the group of nucleic acids that encode H. pylori coat proteins and H. pylori coat proteins as set forth in Table 1. However, any nucleic acid an acid encoding an immunogenic H. pylori protein and a H. pylori polypeptide, or a portion thereof, may be used in the present invention. These vaccines have therapeutic and / or prophylactic uses.

In one aspect, the present invention comprises a vaccine composition for protection against H. pylori infection comprising at least one immunogenic fragment of H. pylori protein and a pharmaceutically acceptable carrier. Preferred fragments include peptides de-BKY ^- at least 10 amino acid residues, more preferably a length of approximately 10-20 amino acid residues, and most preferably a length of approximately 12-16 amino acid residues.

The immunogenic components of the present invention can be obtained, for example, by screening for polypeptides produced recombinantly from the corresponding nucleic acid fragment encoding the entire H. pylori protein. Further, fragments can be synthesized chemically using techniques known in the art, such as Merrifield f-Moc or t-Boc solid phase synthesis.

In one embodiment, the immunogenic components are identified by the ability of the peptides to stimulate T cells. Peptides that stimulate T cells, as determined, for example, in a T cell proliferation assay or cytokine secretion, are defined herein to comprise at least one epitope. It is believed that T cell epitopes are involved in initiating and developing an immune response against a protein allergen that is responsible for the clinical symptoms of allergy. These T cell epitopes are believed to trigger T-helper cell events by binding to a suitable HLA molecule on the surface of the antigen-presenting cell, stimulating a T cell subpopulation with the corresponding T cell receptor for the epitope. These events lead to T cell proliferation, lymphokine secretion, local inflammatory response, mobilization of other immune system cells to the antigen / T cell interaction site, and activation of the B cell cascade, resulting in a '' ·· '·' «'···· < 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9

I · ··· «production of antibodies. The T cell epitope is an essential element, or the smallest unit for recognition by the T cell receptor, and contains essential amino acids. .receptor recognition. (for example, about .6 *: or .7 amino acid residues). "Amino acid sequences" that mimic these T cell epitopes as well. they also fall within the scope. of the present invention.

In another embodiment, the immunogenic components of the present invention are identified by means of a vaccine vaccine. The basic protocol is based on the idea that the expression of libraries containing all or part of the genome of a pathogen, such as the H. pylori genome, can induce protection when used for genetic immunization of a host. This immunization with an expression library (ELI) is analogous to expression cloning and comprises the reduction of genomic expression libraries of a pathogen, for example H. pylori, into plasmids that can act as genetic vaccines. Plasmids can also be designed

9 »O Ι-'ΧΤ F 1-F · 1 F FV * O 4“ «? If · If · ♦ “F \, n rif · ^W

JTkV ^ J-Cl V Jf.

stimulate antibody response. These genetic adjuvants can be inserted at distant sites and can act both extracellularly and intracellularly.

This is a new approach for vaccine production that has many advantages as living / attenuated pathogens but no risk of infection. The expression library of the pathogen DNA is used to immunize the host, allowing to achieve the same antigen presentation effects as achieved with the live vaccine, but without 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 genome sequencing, can be used to immunize a host. The feasibility of this approach has been demonstrated on Mycoplasma pulmonis (Barry et al., Nature 377: 632 - 635, 1995), where partial expression libraries are also used.

Mycoplasma pulmonis, the natural pathogen of rodents, has induced 9 9 * 0, 9 -9 9, 9 * 9, 9 * 9 9 -9 9 9 19 '0 0 ^ 9 · 0-> · .9 0 9 00 0

9, 9 0 9 9 9

0 0 0 0 00 ι9 0 9 .0 9 00 protection against pathogen infection.

ELI is a technique that allows the production of non-infectious multilateral vaccines, although little is known about the biology of the pathogen, because ELI uses the immune system to screen for genes that are candidates for this use. Once isolated, these genes can be used as genetic vaccines or for the development of recombinant protein vaccines. Thus, ELI allows the production of vaccines in a systematic, highly mechanized manner.

Examination of immunogenic components can be performed using one or more different assays. For example, the stimulating activity of a T cell peptide is tested in vitro by contacting a peptide that is believed or known to be immunogenic with an antigen presenting cell, which then presents it on suitable MHC molecules in a T cell culture. The presentation of an immunogenic H. pylori peptide with a suitable MHC molecule to T cells together with the necessary concomitant stimulation results in signal transduction to T cells that produce increased amounts of cytokines, particularly interleukin-2 and interleukin-4. Culture supernatant can be obtained and tested for interleukin-2 and other known cytokines. For example, any of a number of conventional interleukin-2 assays may be used, such as the assay described in Proc. Nati. Acad. Sci. USA 86: 1333 (1989), the portions of which are related to this assay are hereby incorporated by reference. The interferon production assay kit is also available from Genzyme Corporation (Cambridge, MA).

Alternatively, a conventional assay for measuring T cell proliferation measures the incorporation of tritium-labeled thymidine. T cell proliferation can be measured in vitro by determining the amount of ³ H-labeled thymidine incorporated into the replicating DNA of the cultured cells. Thus, the rate of DNA synthesis and thus the rate of cell division can be quantified.

(· 'Ί · 0-0 ·% ·' ···· '·.' · · ^Ί · .0 0 '0' 0 0 <0> · 0 · {0

0 0 0 0'00 0 0. '0 0' 0

0: 0 0

The vaccine compositions or formulations of the present invention comprising one or more immunogenic components (for example, an H polypeptide, pylori or fragment thereof, or a nucleic acid encoding an H. pylori polypeptide or fragment thereof) preferably comprise a pharmaceutically acceptable carrier. The term pharmaceutically acceptable carrier includes any solvents, dispersing media, coatings, antibacterial and antifungal agents, isotonic and absorption retarding agents and the like which are compatible with pharmacy by administration; Suitable pharmaceutically acceptable carriers include, for example, water, saline, phosphate buffered saline, dextrose, glycerol, ethanol, and the like, as well as combinations thereof. Pharmaceutically acceptable carriers may further comprise small amounts of excipients, such as wetting or emulsifying agents, preservatives, or buffers, which increase the durability or potency of the H. pylori nucleic acid or polypeptide. Preferably, the vaccine compositions of the present invention comprising H. pylori polypeptides are administered together with a suitable adjuvant and / or delivery system as described herein.

It will be appreciated by those skilled in the art that a therapeutically effective amount of the DNA or protein of the present invention will depend, inter alia, on the administration protocol, the single dose of the H. pylori nucleic acid or polypeptide administered, whether the protein or nucleic acid is administered in combination. other therapeutic agents, the immune system and patient's health, and the therapeutic activity of a single protein or nucleic acid.

The vaccine compositions are usually administered parenterally, for example by injection, either subcutaneously or intramuscularly. Intramuscular immunization techniques are described in Wolff et al., (1990) '' (1990) ''. · 9

9 99 99

Science 247: 1465-1468 and Sedegah et al., (1994) Immunology

91: 9866-9870. Other routes of administration include oral and pulmonary formulations, suppositories and transdermal formulations. Oral immunization is preferable to parenteral techniques for inducing protection against H. pylori infection. Czinn et al., (1993) Vaccine 11: 637-642.

Oral formulations include such normally employed additives such as mannitol, lactose, starch, magnesium stearate, sodium saccharine, cellulose, magnesium carbonate and the like, all in pharmaceutical 'čístofě ^-. ------------------ --------------- ---------------- V in one embodiment, the vaccine composition comprises an adjuvant, as a pharmaceutically acceptable carrier. Examples of suitable adjuvants for use in the vaccine compositions of the present invention include, but are not limited to, aluminum hydroxide; N-acetyl-muramyl-L-threonyl-D-isoglutamine (thr-MDP); N-acetyl-nor-muramyl-L-alanyl-D-isoglutamine (CGP 11637, also referred to as nor-MDP); N-acetylmuramyl-L-alanyl-D-isoglutamyl-L-alanine-2- (1'-2'-dipalmitoyl-sn-glycero-3-hydroxyphosphoryloxy) ethylamine (CGP 19835A, also referred to as MTP-PE) ; RIBI, which contains three components from bacteria; monophosphoryl lipid A; trehalose dimycoloate; cell wall skeleton (MPL-TDM-CWS) in 2% squalene / Tween 80 emulsion; and choleratoxin. Further, nontoxic choleratoxin derivatives, including its B subunit, and / or conjugates or genetically engineered preparations of H. pylori polypeptide with choleratoxin or its B subunit, procholeragenoid, mycotic polysaccharides, including schizophylllan, muramyldipeptide, derivatives of muramyldipeptide, esters of muramyldipeptide, esters of muramyldipeptide, E. coli toxin, non-H. pylori with bacterial lysates, block polymers or saponins.

In another embodiment, the vaccine composition comprises a transmission system as a pharmaceutically acceptable carrier. Suitable transmission systems for use in the vaccine compositions of

• '<· ··· ··· ·· <·· · <· ·; · · »· • · • · # · · ♦ · · (· · • · · · · • - · «· <· · · · · · · · · ·· ··

of the present invention include microcapsules or immunostimulatory complexes (ISCOMs), cochleats, or liposomes, genetically engineered live vectors such as viruses or bacteria, and recombinant (chimeric). virus-like particles such as bluetongue.

In another embodiment, the vaccine composition comprises both a delivery system and an adjuvant.

* '

Systems for administration to humans may include enteric release capsules to protect the antigen from the acidic environment in the stomach and containing the H. pylori polypeptide in insoluble form as a fusion protein. Suitable carriers for the vaccines of the present invention are enteric coating capsules and polylactide-glycolide microspheres. Suitable diluents are 0.2 N NaHCO ₃ and / or saline.

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

The amount of adjuvant used will depend on the type of adjuvant used. For example, if the mucosal adjuvant is choleratoxin, it is preferably used in an amount of 5 µg to 50 µg, for example 10 µg to 35 µg. When a microcapsule form is used, the amount used will depend on the amount used in the microcapsule matrix to achieve the desired dosage. Determining this quantity is for 'tt' · tttt ·· tttt ·· · tt · tt · tt tttt tt ···· tt tttt 1 · · tt tttttt · - ·· • tttttt ·. · • tttttt · ·· · ·· · »experts.

It will be appreciated by those skilled in the art that the optimum dose will be more or less dependent on the patient's body weight, disease, mode of administration, and other factors. It will also be appreciated by those skilled in the art that the dose may be determined based on results obtained for other known oral vaccines, such as E. coli lysate vaccine (6 mg per day to 540. mg per day) and "over-purified ^- antrigen enterotoxic; E. coli (4 doses of pomg) (Schulman et al., J. Urol. 150: 917-921 (1993)); Boedecker et al., American Gastroenterological Assoc. 999: A-222 (1993)).

The number of doses will depend on the disease, the composition and the efficacy as determined in clinical trials. Without limitation, treatment can be administered as 3 to 8 doses for primary immunization within 1 month (Boedecker et al., American Gastroenterological Assoc.

999: A-222 (1993)).

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

It will be appreciated by those skilled in the art that some vaccine compositions of the present invention are useful only to prevent H. pylori infection, some are useful only for the treatment of H. pylori infection, and some are useful for both the treatment and prophylaxis of H. pylori infection. In a preferred embodiment, the vaccine composition of the present invention provides protection against H. pylori infection by stimulating humoral and / or cellular immunity against H. pylori. It should be clear that the alleviation of any clinical symptoms of H. pylori infection is finite »· · ♦» 0 0000

000 · 0 00

00 0 0 0 0 0

0 0 0 0

0 000 · 00 0 0 0 0 00 ·· clinical objective, including reducing the dose of medication used to treat H. pylori disease, or increasing antibody protection in the serum or mucosa of patients.

VII. Antibodies reactive with H. pylori polypeptides

The invention also includes antibodies specifically reactive with a H. pylori polypeptide. Anti-protein / anti-peptide antisera or monoclonal antibodies can be prepared using standard techniques (See, for example, Antibodies: A Laboratory Manual, published by Harlow and Lane (Cold Spring Harbor Press: 1988)). Mammals, such as mice, hamsters or rabbits, can be / immunized with the immunogenic form of the peptide. Techniques for inducing immunogenicity of a peptide or protein include conjugation to a carrier or other techniques well known in the art. The immunogenic portion of the H. pylori polypeptide may be administered in the presence of an adjuvant. Progress of immunization can be monitored by detecting antibody titers in plasma or serum. Standard ELISA or other immunoassays can be used with an immunogen such as an antigen to assess antibody levels.

In a preferred embodiment said antibodies are immunospecific for antigenic determinants of H. pylori polypeptides of the present invention, for example for antigenic determinants of polypeptides of the present invention listed in the sequence listing, or closely related human or non-human mammalian homologs (e.g. 90% homologous, preferably homologous (at least 95%). In yet another preferred embodiment of the invention, the anti-H. pylori antibodies are not significantly cross-reactive (i.e., react specifically) with a protein having, for example, 80% homology to the sequence of the present invention listed in the sequence listing. The term is not significantly cross-reactive means that the antibody has a binding affinity for ·· φφ Φ ···

ΦΦ ·· φ · φ · φ φ φφφφ φ φ φφφ φφφ φ φ «

The protein is less than 10%, preferably less than 5%, and most preferably less than 1% of the binding affinity for the protein of the present invention listed in the Sequence Listing. In the most preferred embodiment, there is no cross-reactivity between bacterial and mammalian antigens.

The term antibody as used herein includes fragments thereof that are also specifically reactive with H. pylori polypeptides. Antibodies can be fragmented using conventional techniques and can be assayed more readily in the same manner as described for whole antibodies. For example, F (ab ') ₂ fragments can be made by treating the antibody with pepsin. The resulting F (ab ') ₂ fragment can be processed such that disulfide bonds are reduced to yield Fab' fragments. The antibody of the present invention further comprises bispecific and chimeric molecules having a portion reactive against H. pylori.

Both monoclonal and polyclonal antibodies (Ab) 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 effect of H. pylori polypeptides and allow study of the role of a single H. pylori polypeptide of the present invention in aberrant or unwanted intracellular signaling as well as studies of normal cellular functions of H. pylori using microinjection of antibodies against H. pylori polypeptides of the present invention.

Antibodies that specifically bind to H. pylori epitopes can also be used for immunohistochemical staining of tissue samples to assess the amount and pattern of expression of H. pylori antigens. Antibodies to H. pylori polypeptides can be used diagnostically in immunoprecipitation and immuno-blotting to detect and evaluate the amount of H. pylori in tissues or body fluids, where these techniques are part of clinical trials.

Similarly, the ability to monitor levels of H. pylori polypeptide in an individual allows the efficacy of a given treatment to be determined: an individual with such a disease. The level of H. pylori 'polypeptide can be measured in body fluid cells, such as urine samples, or can be measured in tissues, such as in gastric biopsies. Diagnostic tests using antibodies against ... H. Pylori may include, for example, immunoassays designed for early diagnosis of H. pylori infection. The present invention can also be used as the method ^- for-děteRčíAprOtilátek contained in samples from individuals infected by this bacterium using specific H. pylori antigens.

Another application of antibodies against H. pylori polypeptide is the immunoassay of cDNA libraries constructed in expression vectors such as lambdag11, lambdagt18-23, lambdaZAP and lambdaORF8. Mediator libraries of this type having the coding

ΤΊ ΤΊ 0 0 * + ΖΛΤΓΟ vt i «t rza c ** ^ ** · ^ rv» Λτν · *** · · *** “? rvn / - »a-xiwv-x * WliVU. v IWIILV produce fusion proteins. For example, the lambda tag will produce fusion proteins whose amino terminus consists of β-galactosidase amino acid sequences and whose carboxy terminus consists of a foreign protein. Antigenic epitopes of said H. pylori polypeptide can then be detected by antibodies, for example, in the reaction of nitrocellulose filters drawn from infected plates with antibodies against the H. pylori polypeptide. The phage screened with this assay can be isolated from the infected plate. Thus, the presence of a homologous H. pylori gene can be detected and the gene can be cloned from other species and alternative isoforms (including splice variants) can be detected and cloned.

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

The nucleic acids, polypeptides, and antibodies of the present invention can be combined with other agents and components to form a kit. Kits for diagnostic purposes typically contain i-nucleic acids, polypeptides, or antibodies in vials or other suitable containers. The kits typically include additional reagents for performing hybridization reactions, polymerase chain reactions (PCR), or for reconstituting lyophilized components such as aqueous media, salts, buffers, and the like. The kits may also contain sample processing agents such as detergents, chaotropic salts and the like. The kits may also include immobilizing agents such as particles, carriers, wells, rods, and the like. The kits may also include labeling means such as dyes, development agents, radioisotopes, fluorescent agents, luminescent or chemoluminescent agents, enzymes, intercalating agents, and the like. Using the nucleic acid and amino acid sequences disclosed in the present invention, one can easily assemble kits for a particular purpose in the art. The kits may further comprise instructions for use.

IX Drug screening assays using H. pylori polypeptides

In view of the availability of the purified and recombinant H. pylori polypeptides of the present invention, the invention includes assays that can be used to screen for drugs that are either agonists or antagonists of normal cellular function, in this case said H. pylori polypeptides, or their role in intracellular signaling. Such inhibitors or potentiators may be useful as novel therapeutic agents against H. pylori infections in humans. Various types of assays can be used which are, in light of the present invention, clear to those skilled in the art.

• ·

In many drug discovery programs that test a library of compounds and natural extracts, high throughput tests are desirable to maximize the number of compounds tested over a given period of time. Assays that are performed in cell-free systems, such as may be derived from purified or semi-purified proteins, are often preferred as a primary screen because they can be designed to allow rapid development and relatively easy detection of alterations in the target molecule that are caused by the test compound. In addition, the effect of cellular toxicity and / or bioavailability of the test compound may be neglected in the in vitro system, and this assay is primarily directed to the effect of the drug on the target molecule as manifested in altering the binding affinity to other proteins or altering enzymatic enzymes. properties of the target molecule. Accordingly, in an exemplary screening assay of the present invention, the desired compound is contacted with an isolated and purified H. pylori polypeptide.

Screening assays can be performed 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 the polypeptide induces a detectable reaction product. The efficacy of the compound can be evaluated according to the crooked dose-response data obtained using different concentrations of the test compound. In addition, a control test may also be performed to obtain baseline values for comparison. Suitable reaction products include, for example, products with different absorption, with fluorescence or chemiluminescence properties that allow automatic detection. Many synthetic or natural compounds can be tested in this assay to identify those compounds that inhibit or potentiate the activity of the H. pylori polypeptide. Some of these compounds may also, directly or after chemical alterations to induce membrane permeability or solubility, also inhibit or potentiate the same activity (e.g. enzymatic activity) in whole living H. pylori cells.

The invention will be further described in the following non-limiting examples. All references and published patent applications cited in this application are hereby incorporated by reference.

DETAILED DESCRIPTION OF THE INVENTION

Example 1: Cloning and Sequencing of H. pylori DNA

H. pylori chromosomal DNA is isolated according to the basic DNA protocol of Schleif RF and Wensink PC, Practical Methods in Molecular Biology, p. 98, Springer-Verlag, NY, 1981, with minor modifications. Briefly, cells are pelleted, resuspended in TE (10 mM Tris, 1 mM EDTA, pH 7.6) and GES lysis buffer (5.1 M guanidinium thiocyanate, 0.1 M EDTA, pH 8.0, 0) is added. , 5% N-lauryl sarcosine). The suspension is frozen and ammonium acetate (NH ₄ Ac) is added to a final concentration of 2.0 M. DNA is extracted, first with chloroform, then phenol-chloroform, and re-extracted with chloroform. The DNA was precipitated with isopropanol, washed twice with 70% EtOH, dried and resuspended in TE.

After isolation, whole H. pylori genomic DNA is not pulsed (Bodenteich et al., Automated DNA Seguencing and Analysis (J.C. Venter ed.), Academic Press, 1994) to a median size of 2000 bp.

After nebulization, the DNA is concentrated and separated on a standard 1% agarose gel. Several fractions corresponding to approximately 900-1300 bp, 1300-1700 bp, 1700-2200 bp, 2200-2700 bp were excised from the gel and purified by the GenClean technique (BiolO1, Inc).

The purified DNA fragments were blunt-ended using T4 DNA

and.

Polymerases. The processed DNA is then ligated into unique BstXI-linker adapters in a 100-1000 fold molar excess. These linkers are complementary to the BstXI digested pMPX vector, while the overlap is not in itself complementary. Therefore, the linkers will not be concatemerized nor will the digested vectors be readily back-ligated. Linker-adapter inserts are separated from incorporated linkers on a 1% agarose gel using GeneClean. Linker-adapter inserts are ligated into each of the 20 pMPX vectors to yield the era of the general library libraries. The vectors contain the lacZ gene outside the reading frame at the cloning site, which moves into the reading frame when the adapter-dimer is cloned, allowing them to be recognized by their blue color.

All further steps were performed according to the multiple DNA sequencing protocols listed in Church G.M. and Kieffer-Higgins S., Science 240: 185-188. 1998. Only major modifications of the protocol are given. Briefly, each of the 20 vectors is transformed into DH5α competent cells (Gibco / BRL, DH5α transformation protocol)). Libraries are assayed by placing on antibiotic plates containing ampicillin, methicillin, and IPTG / Xgal. The plates were incubated overnight at 37 ° C. Successful transformants are then used to cultivate clones and pooled into multiple pools. Clones were harvested and placed in cultures in 40 ml culture medium. The cultures are incubated overnight at 37 ° C. DNA was purified using Qiagen Midi-prep kits and Tip-100 columns (Qiagen, Inc). In this way 100 μg of DNA per sample is obtained. 15 96-well DNA plates are generated to give a 5-10 fold excess of the reading length of approximately 250-300 bases.

These purified DNA samples are then sequenced using multiple DNA sequencing based on chemical degradation techniques (Church GM and Kieffer-Higgins S., Science 240: 185-188, 1998), or using Sequithre (Epicenter Technologies) dideoxy-Sekylation Protocols. Sequencing is electrophoresed and transferred to nylon membranes by direct transfer electrophoresis from 40 cm gels (Richterich P. and Church GM, Methods in Enzymology 218: 187-222, 1993) or by electroblotting (Church, supra). 24 samples were used, 45 correct membranes were produced by chemical sequencing and 8 were produced by dideoxy sequencing DNA was covalently ligated to the membrane by exposure to UV light and hybridized with labeled oligonucleotides complementary to stem sequences on vectors (Church, supra). nonspecifically bound probes and exposed to X-ray f Ilm for individual sequences. After autoradiography, the hybridized probe was removed by incubation at 65 C, ^P and hybridization cycle repeated with another stalk sequence until the membrane is "probed" i O t V »J Λ. 1 - - Λ Μ MA * - - «st. «Μ V» »» VW «4 Λ r

JO ^_ · AJLCIL pxv DCA VCiiUUVCUiC UiCUlV j CU1J Cl pxv UXUCVAJ 'sequenced membrane. Thus, each gel produces a large number of films, each containing new sequence information. Whenever a new spot is processed, it is first probed to the internal standard sequences added to each file.

Digital imaging of films is obtained using a laser scanning densitometer (Molecular Dynamics, Sunnyvale, CA). Digitized images are processed on a computer (VaxStation 4000's) using REPLICA ™ (Church et al., Automated DNA Sequencing and Analysis (J.C. Venter ed.), Academic Press, 1994). Imaging processing includes row placement, contrast adjustment to adjust intensity and resolution differences using chain Gaussian deconvolution. The sequences are then automatically saved in REPLICA ™ and displayed for chain verification before being stored in the project database. The verification is performed by a quick visual inspection of the film, followed by a mouse click on the strip of the displayed film to modify the names of the tastes. Many sequence errors can be detected and corrected because multiple sequence readings cover the same portion of genomic DNA, and thus a corresponding number of sequences are obtained for its determination. Each sequence is automatically assigned an identification number (corresponding to the microtiter plate, probe and line set). This number serves as a permanent sequence identification, so it is possible to identify the original of any sequence without re-viewing the specialized database.

Routine alignment of H. pylori sequences is performed using the FALCON program (Church, Church et al., Automated DNA Sequencing and Analysis (J.C. Venter ed.), Academic Press, 1994). it has been verified that this program is fast and reliable for most sequences. Sequenced portions of the sequence are displayed using a modified version of GelAssemble developed by Genetics

Computer Group (GCG) (Devereux et al., Nuclerc Acids Res. 12):

387-95, 1984) and which is compatible with REPLICA ™. This provides an integrated editor that allows instant recall of many sequence gel images from the REPLICA ™ database, and allows for rapid viewing of sequence sections and verification of gel traces when discrepancies occur between different sequences during alignment.

Example 2: Identification, Cloning and Expression of Recombinant H. pylori DNA Sequences

To facilitate cloning, expression and purification of the membrane and secreted H. pylori proteins, an efficient gene expression system, the pET System (Novagen), for cloning and expression of recombinant proteins in E. coli is selected. The DNA sequence encoding the end of the peptide, His-Tag, is fused to the 3 'end of the desired DNA sequence to facilitate purification of recombinant protein products.

• ··· «

The 3 'end is selected for fusion to avoid altering any 5' end signal sequence. The exception is ppiB, a gene cloned as a control in expression studies. In this study, the H. pylori ppiB sequence contains a DNA sequence coding for His-Tag fused to the 5'-end of the complete gene because the protein product of this gene does not contain a signal sequence and is expressed as a cytosolic protein.

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

Selected sequences (from the DNA sequence listing of the present invention) for cloning from H. pylori J99 strain are prepared for amplification using polymerase chain reaction (PCR) cloning. Synthetic oligonucleotide primers (Table 3) specific for the 5 ', and' 3 'ends of the open reading frames (ORFs) were designed and purchased from GibcoBRL Life Technologies, ¹ Gaithersburg, MD, USA). All primers for the coding sequence (specific for the 5 'end of the sequence) were designed to encode an NcoI cloning site at the 5'-end, except for the HpSeq.4821082, where the NdeI site was used. These primers were designed to allow initiation of protein translation at the site of the methionine residue followed by the valine residue and the coding sequence for the native H. pylori DNA sequence. The exception is the H. pylori sequence 4821082, where the initiating methionine is immediately followed by the remaining native H. pylori DNA sequence. All primers for the antisense sequence (specific for the 3'-end of the H. pylori ORF) contained an EcoRI site at the 5'-end to allow cloning of each H. pylori sequence into the pET-28b reading frame. The vector pET-28b contains a 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 C-terminus) that form the His-stem. The exception is, as was f

Above, the vector for the ppiB gene. A synthetic oligonucleotide primer specific for the 5'-end of the ppiB gene encoded the BamHI site at the 5'-end and the primer for the 3'-end of the ppiB gene encoded the XhoI site at the 5'-end. . ·

Table 3 - Oligonucleotide / primers used for PCR amplification of H. pylori DNA sequences

External proteins Coding primer Reverse primer of membrane ___ 5 '- 3' 5 '- 3'

Protein 16225006 5-TATACCATGGTGGG CGCTAA-3 '(SEQ ID NO: 147) 5'- ATGAATTCGAGTAAG GATTTTTG-3 '(SEQ ID NO: 148) Protein 26054702 5'- TTAACCATGGTGAAA AGCGATA-3 '(SEQ ID NO NO: 149) 5'- TAGAATTCGCATAAC GATCAATC-3 '(SEQ ID NO: 150) Protein 7 &amp; 5- - ATATCCATGGTGAGT TTGATGA-3 '(SEQ ID NO: 151) 5- ATGAATTCAATTTTT TATTTTGCCA-3 '(SEQ ID NO: 152) Protein 29479681 5'- AATTCCATGGTGGGG GCTATG-3 '(SEQ ID NO NO: 153) 5- ATGAATTCTCGATAG CCAAAATC-3 '(SEQ ID NO: 154) Protein 14640637 5'- AATTCCATGGTGCAT 'AACTTCCATT-3' (SEQ ID NO: 155) 5'- AAGAATTCTCTAGCA TCCAAATGGA-3 '(SEQ ID NO: 156)

Periplasmatic /

Secreted proteins

Protein 30100332 5'-ATTTCCATGGTCATG TCTCATATT-3 '(SEQ ID NO: 157) 5'- ATGAATTCCATCTTT TATTCCAC-3 '(SEQ ID NO: 158) Protein 4721061 5'-AACCATGGTGATTT TAAGCATTGAAAG-3 '(SEQ ID NO: 159) 5'- AAGAATTCCACTCA AAATTTITTATAAGAG-3 '(SEQ ID NO: 160)

· «··· · '· ··· ···

Other surface proteins

Protein 4821082 5’-GATCATCCATATGTT ATCTTCTAAT-3 '(SEQ IDNO: 161) 5’- TGAATTCAACCATTT TAACCCTG-3 '(SEQ ID NO NO: 162) Protein 978477 5'-TATACCATGGTGAA ATTTTTTCTTTTA-3 ' 5'- AGAATTCAATTGCG 1 (SEQ ID NO: 163) TCTTGTAAAAG-3 ' (SEQ ID NO: 165)

Inner membrane protein

Protein 26380318

5-TATACCATGGTGAT

GGACAAACTC-3 '(SEQ

5'-ATGAATTCCCACTT GGGGCGATA-3 '(SEQ

Cytoplasmic protein ppi

5'-TTATGGATCCAAAC CAATTAAAACT-3 '(SEQ ID NO: 167)

5'-TATCTCGAGTTATA GAGAAGGGC-3 '(SEQ ID NO: 168)

Genomic DNA prepared from H. pylori J99 strain (ATCC # 55679; deposited by Genome Therapeutics Corporation, 100 Beaver Street, Waltham, MA 02154) is used as a template DNA source for PCR amplification reactions (Current Protocols in Molecular Biology, John Wiley and Sons, Inc., F. Ausubel et al., eds., 1994). To amplify the DNA sequence containing the H. pylori ORF, genomic DNA (50 ng) is placed in a reaction vessel containing 2 mM MgCl ₂ , 1 micromole of synthetic oligonucleotide primers (encoding α.

• 0 * • 00 0

0 • · '· 0 ······· ····

·· 0 ·· 0 ·

Reverse primers) complementary to and contiguous to the defined H. pylori ORF, 0.2 mM each deoxynucleotide. dATP, .dGTP, dCTP, dTTP and 2.5 units of thermostable DNA polymerase (Amplitaq, Roche Molecular Systems, Inc., Branchburg, NJ, USA) in a final volume of 100 μΐ. The following temperature cycles were used to obtain amplified DNA products for each ORF using a Perkin Elmer Cetus / GeneAmp PCR System 9600 to perform temperature cycles.

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

Denaturation at 94 ° C for 2 minutes;

cycles at 94 ° C for 15 s, 30 ° C for 15 s and 72 ° C for 1.5 minutes cycles at 94 ° C for 15 s, 55 ° C for 15 s and 72 ° C for 1, 5 minutes rl τ

-‘- J or »

Protein 16225006;

Denaturation at 94 ° C for 2 minutes;

cycles at 95 ° C for 15 s, 55 ° C for 15 s, and 72 ° C for 1.5 minutes

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

Protein 4721061;

Denaturation at 94 ° C for 2 minutes;

cycles at 94 ° C for 15 s, 36 ° C for 15 s and 72 ° C for 1.5 minutes cycles at 94 ° C for 15 s, 60 ° C for 15 s and 72 ° C for 1, 5 minutes

Reactions were terminated at 72 ° C for 6 minutes.

• ·

Protein 26380318; . 'Denenation at 94 ° C for 2 minutes;

cycles at 94 ° C for 15 sec, 38 ° C for 15 sec and 72 ° C for 1.5 min cycles at 94 ° C for 15 sec, 62 ° C after 15 sec and 72 ° C for 1 sec The reactions were terminated at 72 ° C for 6 minutes.

Protein 14640637;

Denaturation at 94 ° C for 2 minutes;

cycles at 94 ° C for 15 s, 33 ° C for 15 s and 72 ° C for 1.5 minutes cycles at 94 ° C for 15 s, 55 ° C for 15 s and 72 ° C for 1, 5 minutes

Reactions were terminated at 72 ° C for 6 minutes.

Conditions for ppiB amplification of H. pylori

Denaturation at 94 ° C for 2 minutes;

cycles at 94 ° C for 15 s, 32 ° C for 15 s and 72 ° C for 1.5 minutes cycles at 94 ° C for 15 s, 56 ° C for 15 s and 72 ° C for 1, 5 minutes

Reactions were terminated at 72 ° C for 6 minutes.

Upon completion of the temperature cycles, each amplified DNA sample is washed and purified using a Qiaquick Spin PCR purification kit (Qiagen, Gaithersburg, MD, USA). All amplified DNA samples were digested with NcoI and EcoRI restriction endonucleases (New England BioLabs, Beverly, MA, USA), or in the case of HpSeq. 4821082 (SEQ ID NO: 1309) NdeI and EcoRI (Current Protocols in Molecular Biology, John Wiley &amp; Sons, Inc., F. Ausubel et al., Eds.,

1994). DNA samples are then electrophoresed to 1.0%

NuSieve (FMC BioProducts, Rockland, ME USA) agarose gel. DNA is visualized by exposure to ethidium bromide and irradiation with long wavelength UV light. DNA contained in the agarose gel isolated sections was purified using the Bio 101 GeneClean Kit protocol (Bio 101, Vista, CA, USA).

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

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

After digestion, the DNA inserts are cloned (Current Protocols in Molecular Biology, John Wiley &amp; Sons, Inc., F. Ausubel et al., Ed., 1994) into a pre-digested pET-28b expression vector, except for the amplified insert for ppiB, which was cloned into the expression vector pET-28a. The ligation reaction products are then used to transform E. coli strain B121 (Current Protocols in Molecular Biology, John Wiley &amp; Sons, Inc., F. Ausubel et al., 1994) as described below.

Transformation of competent bacteria by recombinant plasmids

Competent bacteria, E. coli strain BL21 or E. coli strain BL21 (DE3) are transformed with recombinant pET expression plasmids carrying cloned H. pylori sequences using standard techniques (Current Protocols in Molecular Biology, John Wiley and others).

100 ALIGN!

Sons, Inc., F. Ausubel et al., Eds., 1994). Briefly, 1 μΐ of the ligation reaction mixture is mixed with 50 μΐ of electrocompetent cells and a high voltage pulse is performed, after which the samples are incubated in 0.45 ml SOC medium (0.5% yeast extract, 2.0% trypton, 10 mM NaCl, 2.5 mM KCl, 10 mM MgCl ₂ , 10 mM MgSO 4 and 20 mM glucose) at 37 ° C with shaking for 1 hour. Twilight samples are then propagated on LB agar plates containing 25 gg / ml kanamycin sulfate by overnight culture. Transformed BL21 colonies are then harvested and analyzed for cloned inserts. as described belowT

Identification of recombinant pET expression plasmids carrying H. pylori sequences

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

Isolation and preparation of plasmid DNA from BL21 transformants

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

Expression of recombinant H. pylori sequences in E. coli

The 101 pET vector can be propagated in E. coli, strain K-12, for example V.HMS174,,, JM109, DH5, etc., for cloning or plasmid preparation. Expression hosts include E. strains

coli containing a chromosomal copy of the T7 gene ^; ŘNÁ .polymerase. These hosts are: bacteriophage DE3 lysogens, anlambda derivative that contains the LacI gene, the lacUV5 promoter, and the T7 RNA polymerase gene. The T7 RNA polymerase is induced by the addition of isopropyl BD-thiogalactoside (IPTG) and the T7 RNA polymerase transcribes any protein plasmid, such as pET-28b, containing the T7 promoter and gene of interest. The strains used include: BL21 (DE3) (Studier, F: W., Rosenberg, AHDunn, JJ, and Dubendorff, JW (1990)).

Meth. Enzymol. 185: 60-89).

For the expression of recombinant H. pylori sequences, 50 ng of plasmid DNA isolated as described above is used to transform competent BL21 (DE3) bacteria as described above (obtained from Novagen as part of the pET expression system kit). The lacZ gene (for β-galactosidase) is expressed in the pET system as described for the recombinant construction of H. pylori. The transformed cells are cultured in SOC medium for 1 hour and then the culture is plated on LB plates containing 25 µg / ml kanamycin sulfate. The next day, colonies of bacteria are harvested and cultured on LB medium containing kanamycin sulphate (25 μg / ml) to an optical density of 0.5 to 1.0 OD units at 600 nM when 1 millimolar IPTG is added to the culture for 3 hours for induction gene expression of recombinant H. pylori DNA constructs.

Following induction of IPTG gene expression, bacteria are pelleted by centrifugation using a Sorvall 'RC-3B centrifuge at 3500 x g for 15 minutes at 4 ° C. The pellets are resuspended in 50 ml cold 10 mM Tris-HCl, pH 8.0, 0.1 M NaCl and 0.1 mM EDTA (STE buffer). The cells are then centrifuged at 2000 x g for 20 minutes at 4 ° C. The wet pellets are weighed and frozen at -80 ° C until they are

102 of E. coli were used for protein purification.

Example 3: Purification of recombinant proteins

Analytical methods

Concentrations of purified protein preparations were spectrophotometrically using absorbance coefficients calculated from the amino acid content (Perkins, S.J., 1986, Eur. J.

Biochem. 157: 1-69--1-80. Protein concentrations are also measured by the method of Bradford, M.M. (1976) Anal. Biochem. 72: 248-254, and Lowry, O.H., Rosebrough, N., Farra, A.L. and Randall, R.J. (1951) J. Biol. Chem. 193, pp. 265-275, using bovine serum albumin as 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 are skeletal muscle rabbit myosin (200 kDa), E. coli (-) galactosidase (116 kDa), rabbit muscle phosphorylase (116 kDa), bovine serum albumin (66.2 kDa), ovalbumin (45 kDa), bovine carbonianhydrase (31 kDa), soybean trypsin inhibitor (21.5 kDa), egg white lysozyme (14.4 kDa) and bovine aprotinin (6.5 kDa).

1. Purification of soluble proteins

All steps were performed at 4 ° C. The frozen cells are thawed, resuspended in 5 volumes of lysis buffer (20 mM Tris, pH 7.9, 0.5 M NaCl, 5 mM imidazole with 10% glycerol, 0.1% 2-mercaptoethanol, 200 µg / ml lysozyme, 1 mM phenylmethylsulfonyl fluoride (PMSF) and 10 µg / ml each of leupeptin aprotinin, pepstatin, L1-chloro-3- [4-tosylamido] -7-amino-2-heptanone (TLCK), L1-chloro-3- [4- tosylamido] -4-phenyl-2-butanone (TPCK) and soybean trypsin inhibitor and are excited by several rounds

103 on a small volume microfluidizer (Model M-110S, Microfluids International Corporation, Newton, MA). The resulting homogenate is treated with 0.1% Brij 35 and centrifuged at. 100000 x g for 1 hour to obtain a clear supernatant (crude extract).

After filtration through a 0.8 µs Suport filter (Gelman Sciences, FRG), the crude extract is placed directly in Ni ² * -nitriltriacetate-agarose (NTA) with a 5 ml bed volume (Hochuli, E., Dbeli, H. and Schacheer, A. - (- 3.-987) -J- Chromatography + 4TT1 177 - I84j pre-equilibrated in lysis buffer containing 10% glycerol, 0.1% Brij 35 and 1 mM PMSF. bed volumes) of lysis buffer containing 10% glycerol, 0.1% Brij 35 and eluted sequentially with lysis buffer containing 10% glycerol, 0.05% Brij 35, mM PMSF and 20, 100, 200 and 500 mM imidazole. monitored by absorbance at OD _zao and peak fractions were analyzed by SDS-PAGE. fractions containing the recombinant protein.eluuji at 100 mM imidazole.

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

Fractions containing recombinant proteins from Ni ² * -NTA agarose columns were collected and concentrated to approximately 5 ml by centrifugal filtration (Centriprep-10, Amicon, MA) and loaded directly into 180 ml (1.6 x 91 cm) columns containing Sephacryl S-100 HR gel filtration medium equilibrated in buffer A (10 mM HEPES, pH 7.5, 150 mM NaCl, 0.1 mM EGTA) and washed with 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 collected and concentrated by centrifugation filtration.

Recombinant protein 7116626,

104

Fractions containing recombinant protein from Ni ² * -NTA agarose columns were collected and dialyzed overnight against 1 liter of dialysis buffer (10 mM MOPS, pH 6.5, 50 mM NaCl, 0.1 µM).

EGTA, 0.02% Brij 35 and 1 mM PMSF). In the morning, remove the fine white precipitate and place the supernatant in 8 ml (8 x 75 mm)

High resolution liquid chromatography monoS columns (Pharmacia Biotechnology, Inc, Piscataway, NJ, USA) equilibrated in buffer B (10 mM MOPS, pH 6.5, 0.1 mM EGTA) containing 50 mM NaCl. The column was flushed with 10 bed volumes of buffer B containing 50 mM NaCl and developed using a 50 ml linear gradient of increasing NaCl concentration (50-500 mM). The recombinant protein 7116626 eluted as a sharp peak at 300 mM NaCl.

2. Purification of insoluble proteins from inclusion bodies

All steps were performed at 4 ° C. Cell pellets are resuspended in lysis buffer with 10% glycerol, 200 µg / ml lysozyme, 1 mM PMSF and 0.1% 2-mercaptoethanol. After passing through the cell disruption apparatus, the resulting homogenate is treated with 0.2% deoxycholate, stirred for 10 minutes and then centrifuged at 20,000 x g for 30 minutes. The pellets are then washed with lysis buffer containing 10% glycerol, 10 mM EDTA, 1% Triton X-100, 1 mM PMSF and 0.1% mercaptoethanol, followed by several washes with lysis buffer containing 1 M urea, 1 mM PMSF and 0.1 %

2-mercaptoethanol. The resulting white pellet is composed mainly of inclusion bodies, there are no undamaged cells and membrane material.

Recombinant proteins 26054702, 16225006, 30100332, 4721061

The following steps were carried out at room temperature. Purified

The inclusion bodies are dissolved in 20 ml of 8.0 M urea in lysis buffer with 1 mM PMSF and 0.1%. 2-mercaptoethanol and incubation at room temperature for 1 hour. Undissolved material is removed by centrifugation. The clear supernatant is filtered, then loaded onto a Ni ² NTA agarose column pre-equilibrated in 8.0 M urea in lysis buffer. The column is 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 sequentially with a 8 M urea, 1.0 mM PMSF and 0.1% 2- mercaptoethanol and 20, 100, 200 and 500 mM imidazole. Fractions were monitored for absorbance at _0D20 and the peak fractions were analyzed by SDS-PAGE. Fractions containing the recombinant protein eluted at 100 mM imidazole.

Recombinant proteins 29479681, -26380318 containing inclusion bodies are dissolved in buffer B containing 8 M urea, 1.0 mM PMSF and 0.1% 2-mercaptoethanol and incubated at room temperature for 1 hour. Undissolved material is removed by centrifugation at 20,000 x g for 30 minutes and the clear supernatant is loaded into a 15 ml (1.6 x 7.5 cm) SP-Sepharose column previously equilibrated in buffer B,

M urea, 1 mM PMSF, 0.1% 2-mercaptoethanol. After washing the column with 11 bed volumes, the column is developed using a linear gradient from 0 to 500 mM NaCl.

Dialysis and concentration of protein samples

Urea is slowly removed from the protein samples by dialysis against Tris-buffered saline (TBS; 10 mM Tris pH 8.0, 150 mM NaCl) containing 0.5% deoxycholate (DOC) with a gradual reduction in urea concentration: · 6 M, 4 M, 3 M, 2 Μ, 1 M, 0.5 M and finally TBS without urea. Each dialysis step i

and

106 '· · performed for at least 4 hours at room temperature.

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

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

Table 4

Identif. E. Homolog Symbol Bacterial b. Way Relative Final Ingredients sequence identified homol. fraction used cleaning MW na conc. ionof. J99 BLAST gene for recombinant purification SDS-PAGE gel , purified protein buffer

of proteins

External membrane proteins

16225006 P28635 YEAC Inclusion bodies His-stop sign 18 kDa 5 mg / ml (B) 26054702 P15929 flgH Inclusion bodies His-stop sign 37 kDa 1.18 mg / ml (B) as dry pellets 7116626 P26093 e (P4) Soluble fractions His-stop sign 29 kDa 0.8 mg / ml 1.85 mg / ml AND C 29479681 P13036 fecA Inclusion bodies SP- Sepharosa 23 kDa 2.36 mg / ml 0.5 mg / ml (B) (B) as dry pellets 14640637 P16665 TPF1 Soluble fractions His-stop sign 17 kDa 2.4 mg / ml AND

gel filtration S100 HR

107 ····

Periplasmic / secreted proteins

3010032 P23847 dppA Inclusion bodies His-stop sign llkDa 2.88 mg / ml (B) 4721061 P36175 GCP Inclusion bodies His-stop sign 38 kDa 2.8 mg / ml (B) Other surface proteins 4821082 P08089 M protein Inclusion bodies His-stop sign 20 kDa 1.16 mg / ml (B) FBP54 Inclusion Bodies— SP- Sepharosa 44 kDa 2.56 mg / ml OJ mg / ml (B) 978477 L28919 (B)

Inner membrane proteins 26380318 P15933 fliG Inclusion bodies SP-11 kDa Sepharosa 22 mg / ml (B) His-stem control proteins P0O722 iačZ OUlUUllUi imn.vv It is 116 kDa gel filtration S200 HR 10 mg / ml AND ppiB Soluble fractions His-stem 21 kDa gel filtration S100 HR 4.4 mg / ml AND

Buffer composition:

A: 10 mM HEPES pH 7.5, 150 mM NaCl, 0.1 mM EGTA B: 10 mM Tris pH 8.0, 150 mM NaCl, 0.5% DOC C: 10 mM MOPS pH 6.5, 300 mM NaCl, 0, 1 EGTA

107 «444

Example 4: Analysis of H. pylori proteins as candidates for. vaccine

A mouse / H model is used to investigate the immunomodulatory effects of H. pylori proteins. pylori. In many respects, this model mimics H. pylori infection in humans. It is focused on the effect of oral immunization of animals - infected with H. pylori - for testing the concept of therapeutic oral immunotherapy.

Animals

Female SPF BALB / c mice are purchased from the Bomholt Breeding Center (Denmark). They are kept in conventional macrolone boxes with feeding and watering as needed. Animals are 4-6 weeks old when purchased.

Infecting

After at least one acclimatization period, the animals are infected with a type 2 strain (VacA negative) of H. pylori (strain 244 originally isolated from ulcer patients). According to our previous experience, this strain well colonizes the mouse stomach, the bacteria are cultured overnight in Brucella broth supplemented with 10% fetal calf at 37 ° C in a microaerophilic atmosphere (10% CO ₂ , 5% O ₂ ). The animals are administered orally omeprazole (400 μτηοΐ / kg) and 3-5 hours thereafter oral inoculation of H. pylori in the broth (approximately 10 ^s cfu / animal). Positive attachment of infection is confirmed in some animals 2-3 weeks after inoculation.

Antigens

Recombinant H. pylori antigens are selected based on their association with the outer membranes of H. pylori. These antigens are

109 selected from the following groups: (1) outer membrane proteins; (2) periplasmic / secreted proteins; (3) outer surface proteins; and (4) inner membrane proteins. All recombinant proteins are constructed with a hexa-HIS stem for purification and non-H is constructed in the same way. pylori control protein (E. coli β-galactosidase; LacZ).

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

Antigens are listed in Table 5, below.

Table 5: Helicobacter pylori proteins

External membrane proteins

Protein

Protein

Protein

Protein

Protein

7116626

4721061

16225006

29479681

14640637

Periplasmic / secreted proteins Protein 30100332

Other cell envelope proteins Protein 4821082

Flagell associated proteins Protein 26380318

Control proteins β-galactosidase (LacZ) ·· »···

110 ·· · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · ·· ··

Immunization

Ten animals in each group are immunized 4 times over 34 days (day 1, 15, 25 and 35). 'Purified antigens in solution or suspension are administered at a dose of 100 mg / mouse. The animals are also given 10 µg / mouse choleratoxin (CT) as an adjuvant at each immunization. Omeprazole (400 mmol / kg) is administered orally to each animal 3-5. Hepes buffer - + - CT or DOC buffer + CT is administered to infected control animals. Animals are sacrificed 2-4 weeks after the last immunization.‘The general study design is shown in Table 6, below.

···· • ·

111 ·· »·»

Table 6: Study plan for therapeutic immunization

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

Substance < - Mouse strain n = 10 • .Dose / mouse Days administration 1. Controls, PBS 2. Choleratoxin, 10 pg Balb / c Balb / c 0.3 ml 0.3 ml 0,14,24,34 0,14,24,34 3. Protein 16225006, 100 gg CT 10 pg + Balb / c 0.3 ml 0,14,24,34 4. Protein 26054702, 100 gg CT 10 pg + Balb / c 0.3 ml 0,14,24,34 5. Protein 26380318, 100 μg CT 10 μg + Balb / c 0.3 ml 0,14,24,34 6. Protein 29479681, 100 μg CT 10 μg + Balb / c 0.3 ml 0,14,24,34 of . rivLcxn _t IUU CT 10 gg + Balb / c 0.3 mi 0,14,24,34 8. Protein 4721061, 100 μg CT 10 gg. + Balb / c 0.3 ml 0,14,24,34 9. Protein 4821082, 100 μg CT 10 μg + Balb / c 0.3 ml 0,14,24,34 10. Protein 7116626, 100 μg CT 10 μg + Balb / c 0.3 ml 0,14,24,34 11. Protein 14640637,100 μg CT 10 μg + Balb / c 0.3 ml 0,14,24,34

Analysis of infection

Mucosal infections: Mice were sacrificed by CO ₂ and cervical dislocation. The abdominal cavity is dissected and the stomach is removed. After cutting the stomach along the large kurvatura, the stomach is rinsed

112 • saline. Anthra and stomach mucous membranes of mm ² area are individually scraped off by a surgical scalpel.

The scraped mucosa was suspended in Brucella broth and placed on a Blood Skirow selective plate. The plates are incubated under microaerophilic conditions for 3-5 days and the number of colonies is counted. The identity of H. pylori is verified by urease and catalase assays and direct microscopy or Gram staining.

Ureas o t es ts t o c t o c;

Agar Base Concentrate, obtained from DIFCO Laboratories, Detroit, MI (Catalog No. 0284-61-3). The Urea Agar Base concentrate is diluted 1:10 with water. 1 ml of the diluted concentrate is mixed with 100-200 ml of actively growing H. pylori cells. The color change to fuchsin indicates that the cells are urease-positive.

The catalase test is performed as follows. Agent,

Ν, Ν, Ν 'Ν'-tet ^ram etbv' ¹ -T-ι - Fcinvl Pnrií amine. is obtained from Sicrma. St. Louis, MO (Catalog # T3134). Prepare a reagent solution (1% w / v in water). Place H. pylori cells on Whatman filter paper and cover with 1% solution. The change of color to dark blue indicates that the cells are catalase positive.

Serum Antibodies: Serum from blood collected by heart puncture is prepared from all mice. Serum antibodies are identified by conventional ELISA techniques, with specific H. pylori antigens.

Mucosal Antibodies: 50% of the mice are gently scraped on a defined part of the stomach body and 4 cm duodenum to determine the presence of antibodies in the mucosa. Antibody titers are determined by conventional ELISA techniques as well as for serum antibodies.

Statistical analysis: Wilcoxon-Mann-Whitney ranking test is used to determine the significant effects of antigens on

113 ··· · ·· ·

0 0

0 »0 • 00 000 0 9

00 colonization Η. pylori. Ρ <0.05 is considered significant. Since antrum is a major colonization site for Helicobacter, the greatest emphasis is placed on changes in anthra colonization.

Results

Serum Antibodies: Measurable serum specific titer was produced when all CT antigens tested were administered. The highest response was observed ^- pro ¹ protein — 71-16 62 β _pr —protein 4721061, protein --------- 26380318, protein 14640637 and for protein 4821082 (see Figure 1).

Mucosal Antibodies: Specific antibodies to all tested antigens were detected in mucosal samples. The strongest response was found for protein 30100332, then for protein 14640637 and protein 26380318 (see Figure 2).

Effects of therapeutic immunization,

All control animals (BALB / c mice) were well colonized with H. pylori (strain AH244) in both the antrum and stomach body. Of the antigens tested, 3 proteins (protein 4721061, protein 4821082 and protein 14640637) caused a good and significant reduction and / or eradication of H. pylori infection. The degree of anthra colonization was lower after immunization with 7116626 and 26380318 compared to control. The effect of proteins 16225006, 29479681 and 30100332 did not differ from control. The lacZ control protein, i.e., non-H. pylori protein, had no eradication effect and in fact there was a higher Helicobacter colonization compared to HEPES + CT. All data are shown in Figures 3 and 4 for proteins dissolved in HEPES and DOC, respectively. Data are presented as geometric mean values, n = 8-10, Wilcoxon-Mann-Whitney test * = p <0.05; x / 10 = number of mice showing H. pylori eradication to the total number of mice examined • · · ·

114 mice.

ϊ.

The data obtained indicate that all H. pylori associated proteins used in this study, when used as oral immunogens together with oral CT adjuvant, result in stimulation of the immune response as measured by specific serum and mucosal antibodies. Most proteins lead to reduction, and some to complete disappearance of H. pylori colonization in this animal model. Two MěToABy ^ ^- uveďenoj the reduction or disappearance is - due to heterologous protection rather than homologous protection (the polypeptides were based on the sequence obtained by the J99 strain of H. pylori used in the therapeutic immunization studies against a different strain (AH244), indicating the vaccine potential against a a wide variety of H. pylori strains).

The highest antrum colonization was observed in animals treated with non-LacZ protein. Helicobacter sp., Indicating that the effects observed for H. pylori antigens are specific.

Taken together, these data support the use of these H. pylori proteins in pharmaceutical compositions for the treatment and / or prevention of H. pylori infections in humans.

V. Analysis of Helicobacter pylori gene sequence variation

Four genes are cloned and sequenced from several H. pylori strains to compare DNA and derived amino acid sequences, this information is used to determine sequence variation between H. pylori J99 strain and other H. pylori strains isolated from humans.

Preparation of chromosomal DNA

115

»· * ···

Cultures of H. pylori strains (as shown in Table 9) are cultured in BLBB (1% trypton, 1% peptamine, 0.1% glucose, 0.2% yeast extract, 0.5% sodium chloride, 5% fetal beef serum) at 0D ⁶⁰ ° 0.2. The cells are centrifuged on Sorvall RC-3B at 3500 xg at 4 ° C for 15 minutes and the pellet is resuspended in 0.95 ml of 10 mM Tris-HCl, 0.1 mM EDTA (TE). Add lysozyme to a final concentration of 1 mg / ml and SDS at 1% and RNAse A + T1 to 0.5 mg / ml and 5 units / ml, respectively, and incubate at 37 ° C for one hour. Proteinase K is then added to a final concentration of 0.4 mg / ml and the sample is incubated at 55 ° C for more than one hour. Add NaCl at a final concentration of 0.65 M, mix thoroughly and add 0.15 mL of 10% CTAB in 0.7 M NaCl (final concentration is 1% CTAB / 70 mM NaCl) followed by incubation at 65 ° C for 20 minutes. Then the samples are extracted with chloroform: isoamyl alcohol, extracted with phenol and again extracted with chloroform: isoamyl alcohol. DNA was precipitated with either EtOH (1.5-fold volume) or isopropyl alcohol (0.6-fold volume) at -70 ° C for 10 minutes, washed in 70% EtOH and resuspended in TE.

PCR amplification and cloning

Genomic DNA prepared from 12 H. pylori strains is used as a template DNA source for PCR amplification reactions (Current Protocols in Molecular Biology, John Wiley &amp; Sons, Inc., F. Ausubel et al., Ed., 1994). To amplify a DNA sequence containing the H. pylori ORF, genomic DNA (10 ng) is inserted into a reaction vessel containing 2 mM _MgCl2, l micromolar synthetic oligonucleotide primers (forward and reverse primers, see Table 7) complementary to and adjacent to a defined H. pylori ORFs 0.2 mM of each deoxynucleotide triphosphate; dATP, dGTP, dCTP, dTTP and 0.5 units of thermostable DNA polymerase (Amplitaq, Roche Molecular Systems, Inc., Branchburg, NJ, USA) in the final.

4 4 · 4 4 4

444 4 4 · 44 44 4

4444 44 4 4 44 44 · * * 444 4,444

115 ··· · .........

capacity 200 μΐ in two versions.

Table 7 - Oligonucleotide primers used for PCR amplification of H. pylori DNA sequences

External Membrane Proteins

Coding primer. -Reverse primer · - 3 '5' - 3 '

Protein 26054702 (for strains AH4, AH15, AH61, 5294, 5640, AH18 and AH244

TTTAACCATGGTGAAA AGCGATA-3 '(SEQ ID NO: 169) _' 5 -—--- TAGAATTCGCCTCTA AAACTTTAG-3 '(SEQ ID NO: 170) _

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

5’TTAACCATGGTGAAA AGCGATA-3 '(SEQ ID NO: i 71) *

5TAGAATTCGCATAAC GATCAATC-3 '(SEQ ID

Ύ T /> - t \ πυ; i /

Protein 7116626

5’- ATATCCATGGTGAGT TTGATGA-3 '(SEQ ID NO: I73) 5’- ATGAATTCAATTTTT TATTTTGCCA-3 '(SEQ ID NO: 174)

Protein 29479681

Protein 346

5'- AATTCCATGGCTATC CAAATCCG-3 '(SEQ ID NO: 175) 5- ATGAATTCGCCAAAA TCGTAGTATT-3 '(SEQ ID NO: 176) 5’- GATACCATGGAATTT ATGAAAAAG-3 '(SEQ ID NO: 177) 5’- TGAATTCGAAAAAGT GTAGTTATAC-3 '(SEQ IDNO: 178) i

117 · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · ·

999 99 99

The following temperature cycles were used to obtain amplified DNA products for each ORF using a Perkin Elmer Cetus / GeneAmp 'PCR System 9600 to perform temperature cycles. .

Protein 7116626 and protein 346 Denaturation at 94 ° C for 2 minutes;

cycles at 94 ° C for 15 s, 30 ° C for 15 s and 72 ° C for 1.5 min cycles at 94 ° C for 15 s, 55 ° C for 15 s and 72 ° C for 1 , 5 minutes

The reaction is terminated at 72 ° C for 6 minutes.

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

Denaturation at 94 ° C for 2 minutes;

cycles at 94 ° C for 15 sec, 30 ° C for 15 sec and 72 ° C for d / o 1/5 minutes * * cycles at 94 ° C for 15 sec, 55 ° C for 15 sec and 72 ° C for 1.5 minutes

The reaction is terminated at 72 ° C for 6 minutes.

Protein 26054702 and protein 294796813 for strains AH4, AH15,

AH61, 5294, 5640, AH18 and Hp244;

Denaturation at 94 ° C for 2 minutes;

cycles at 94 ° C for 15 s, 30 ° C for 20 s and 72 ° C for 2 minutes cycles at 94 ° C for 15 s, 55 ° C for 20 s and 72 ° C for 2 minutes

The reaction is terminated at 72 ° C for 8 minutes.

Upon completion of the temperature cycles, each pair of samples is combined and used directly for cloning into a pCR cloning vector by the method described below.

118, »ϊ

© © © © © © © 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 • · · ·

9 9 9

99 ti

Cloning of DNA Sequences Η. pylori into the pCR TA cloning vector

All amplified inserts were cloned into the pCR 2.1 vector by the technique described in 'Original TA Cloning Kit (Invitrogen, San Diego, CA). coli as described below.

Transformation of competent bacteria by recombinant plasmids

Competent bacteria, E. coli strain TOPIOF 'or E. coli strain INVaF' are transformed with recombinant pCR expression plasmids carrying cloned H. pylori sequences using standard techniques (Current Protocols in Molecular. Biology, John Wiley and Sons, Inc., F.). Ausubel et al., Eds., 1994). Briefly, 2 μΐ of 0.5 micromolar BME is added to each tube containing 50 μΐΐΐ τλ ^ 4- ——. «- n .. i i 4 * -w-x-» <- ........

VUHCJV. The cells were incubated in ice for 30 minutes. The cells and the ligation mixture were then heat soaked at 42 ° C for 30 seconds and then placed on ice for an additional 2 minutes, after which the samples were incubated in 0.45 ml SOC medium (0.5% yeast extract, 2). 0% trypton, 10 mM NaCl, 2.5 mM KCl, 10 mM MgCl ₂ , 10 mM MgSO 4 and 20 mM glucose) at 37 ° C with shaking for 1 hour. The samples are then propagated on LB agar plates containing 25 µg / ml kanamycin sulfate or 100 µg / ml ampicillin by overnight culture. Transformed TOPIOF 'or INVaF' colonies are then harvested and analyzed for cloned inserts as described below.

Identification of recombinant PCR plasmids carrying H. pylori sequences

Individual TOPIOF 'or INVaF' clones transformed

Recombinant pCR-Η.pylori ORFs were analyzed using PCR amplification of cloned inserts. using the same coding and reverse primers specific for each H. pylori sequence as used for the original PCR reactions of amplification cloning. Successful amplification confirms the integration of H. pylori sequences. to a cloning vector (Current ... Protocols in Molecular Biology, John Wiley &amp; Sons, Inc., F., Ausubel et al., ed.,

1994).

Individual clones of recombinant pCR vectors carrying properly cloned H. pylori ORFs were removed for sequence analysis. Sequence analysis was performed on an ABI Sequencer using a standard protocol (Perkin Elmer) using vector-specific primers (as determined by PCRII or pCR2.1, Invitrogen, San Diego, CA) and ORF-specific sequencing primers such as listed in Table 8 below.

* · T · ' ^{* 1} .

you too. ^?

Table 8 - Oligonucleotide primers used for PCR amplification of H. pylori DNA sequences

External membrane proteins

Coding primer 5 '- 3'

Reverse primer 5 - _ 3.

Protein 26054702 5- CCCTTCATTTTAGAAATC G-3 '(SEQ ID NO: 179) 5’- ATTTCAACCAATTCAAT GCG-3 '(SEQ ID NO: 180) 5’- GCCCCTTTTGATTTGAAG CT-3 '(SEQ ID NO: 181) 5’- TCGCTCCAAGATACCAA GAAGT-3 '(SEQ ID NO: 182) 5’- CTTGAATTAGGGGCAAA GATCG-3 '(SEQ ID. NO: 183) 5'- CTTTGGGTAAAAACGCA TC-3 '(SEQ ID NO: 186) 5’- CGATCTTTGATCCTAATT CA-3 '(SEQ ID NO: 187) 5- ATCAAGTTGCCTATGCT GA-3 '(SEQ ID NO: 188) ATGCGTTTTTACCCAAA ..... GAAGT-3 '(SEQ ID, NO: 184) -,

·· ····

120

5'- ATAACGCCACTTCCTTAT TGGT-3 * (SEQ ID NO: 185) - Protein 7116626 5’- TTGAACACTTTTGATTAT GCGG-3 '(SEQ ID NO: 189) 5‘- GGATTATGCGATTGTTTT ACAAG-3 '(SEQ ID NO NO: 190) 5’- GTCTTTAGCAAAAATGG CGTC-3 '(SEQIDNO: 191) 5- AATGAGCGTAAGAGAGC CTTG-3 * (SEQ ID NO: 192) Protein 29479681 5’- CTTATGGGGGTATTGTC 5'- AGGTTGTTGCCTAAAGA A-3 '(SEQ ID NO: 193) 5'- AGCATGTGGGTATCCAG C-3 '(SEQ ID NO: 194) CT-3 '(SEQ ID NO: 195) 5’- CTGCCTCCACCTTTGATC, -3 '(SEQ ID NO: 196) Protein 346 5’- ACCAATATCAATTGGCA CT-3 '(SEQ ID NO: 197) 5’- ACTTGGAAAAGCTCTGC A-3 '(SEQ ID NO: 198) 5’- CTTGCTTGTCATATCTAG C-3 '(SEQ ID NO: 199) 5’- GTTGAAGTGTTGGTGCT · A-3 * (SEQ ID NO: 20) 5’- CAAGCAAGTGGTTTGGT> TTTAG-3 '(SEQ ID NO: 201) 5- TGGAAAGAGCAAATCAT TGAAG-3 '(SEQ ID NO NO: 202) 5'-. '. GCCCATAATCAAAAAGN _: CCAT-3 '(SEQ ID NO: 203) 5'- CTAAAACCAAACCACTT GCT TGTC-3' (SEQ ID NO: 204) Vector primers 5’- GTAAAACGACGGCCAG3 '(SEQ ID NO: 205) ~ 5’- CAGGAAACAGCTATGAC -3 '(SEQ ID NO: 206)

· · •

In 9 · * * · ·. 9 9 9

9 9 9 9 9 9

999 9 9 9 999 999

9

9,999,999,999,999

121

Results

To determine the frequency of PCR errors in these experiments, five individual clones of protein 26054702 were used. prepared from five individual PCR reaction mixtures from H. pylori strain J99, it secretes over a length of 897 nucleotides. a total of 4485 bases the DNA sequence. The DNA sequences for these five clones were sequenced. compares with the DNA sequence obtained previously using another method, i.e. random general cloning and sequencing. The PCR error rate for these experiments was determined to be 2 bases at 4485 bases, corresponding to an estimated error rate less than or equal to 0.04%.

DNA sequence analysis is performed on four open reading frames identified as genes and amplified by PCR from different Helicobacter pylori strains. Derived amino acid sequences of three of the four open reading frames selected for this study show statistically significant BLA.ST homology with defined proteins of other bacterial species, these ORFs include: protein 260547,02, homologous to val A and B genes encoding the ABC transport protein of F. novicida; protein 7116626, homologous to lipoprotein e (P4) present in the outer membrane of H. influenzae; protein 29479681, homologous to fecA, the outer membrane receptor in the transport of ferric dicitrate in E. coli. Protein 346 has been identified as an unknown open reading frame because it exhibits low homology to sequences in published databases.

To assess the extent of conservation or variation in ORF between different H. pylori strains, changes in the DNA sequence and derived protein sequences are compared to DNA and derived protein sequences of the H. pylori J99 strain (see Table 9, below). Results are reported as percent identity with H. pylori J99 strain sequential random random cloning. For control

122

of any variation in the J99 sequence, each of the four open reading frames is re-cloned and sequenced from the J99 bacterial strain, and the sequence is compared to the sequence that was obtained from inserts cloned by random general sequencing of the J99 strain. the data show that the variation in the DNA sequence ranges from

0.12% difference (protein 346, strain J99) to about 7% difference (protein 26054702, strain AH5) Derived protein sequences either show no variation (protein 346, strain AH18 - and AH24) -, or exhibit up to 7.66% variation in amino acid ---------. ..

sequence (protein 26054702, strain AH5).

Table 9 - DNA sequence analysis of multiple vaccine candidate strains

JD protein no. 26054702 2054702 7116626 7116626 29479681 29479681 346 346 Length of sequenced region 248 ak 746 nk 232 ak 96 nk 182 ak 548 nk 273 ak. 819 nk Test strain Identity amino acid. Identirta nucleotides Identity amino acid. Identity. . nucleotides Identity. , . amino acid. . Identity nnkieok ' Identity, Identity of amino acids. nuldeok J99 100.00% 100.00% 100.00% • 100.00% ♦ 100.00% 100.00% • 99.63% 99.88% AH244 95.16% 95.04% n.d. n.d. 99.09% 96.71% 98.90% 96.45% AH4 95.97% 95.98% 97.84% 95.83% n.d. n.d. 97.80% 95.73% AH5 92.34% 93.03% 98.28% 96.12% 98.91% 96.90% 98.53% 95.73% AH15 95.16% 94.91% 97.41% 95.98% '99.82% 97.99% 99.63% 96.09% AH61 n.d. n.d. 97.84% 95.98% 9927% 97.44% n.d. n.d. 5155 n.d. n.d. n.d. n.d. 99.45% 97.08% 9833% 95.60% 5294 94.35% 94.37% 9828% 95.40% 99.64% 9726% 97.07% 95.48% 7958 9435% 94.10% 97.84% 95.40% n.d. n.d. 99.63% 96.46% 5640 95.16% 94.37% 97.41% 95.69% 99.09% 97.63% 9833% 95.48% AH18 n.d- n.d. 98.71% 95.69% 99.64% 97.44% 100.00% 95.97% AH24 94.75% 95.04% 97.84% 95.40% 9927% 96.71% 100.00% 96.46%

n.d. = not performed

123 · · · · · · · · · · · · · · · · · · · · ·

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

Therapeutic targets are selected from those genes, their protein products are likely to play key roles in basic cellular processes such as cell envelope synthesis, DNA synthesis, transcription, translation, regulation, and colonization / virulence.

The protocol for the deletion of H. pylori gene / ORFs and for the insertion mutagenesis of the kanamycin resistance cassette into identified genes that are essential for the cell is modified from previously published methods (Labigne-Roussel et al., 1988, J. Bacteriology 170, p. 1704-1708; Cover et al., 1994, J. Biological Chemistry 269: 10566-10573; Reyrat et al., 1995, Proc. Natl Acad. Sci. 92: 8768-8772). As a result, the gene is knocked out. ...

Identification and cloning of H. pylori gene sequences

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

Genomic DNA prepared from H. pylori HpJ99 strain (ATCC # 55679; deposited by Genome Therapeutics Corporation, 100 Beaver Street, Waltham, MA 02154) was used as a template DNA source for

124

• ·· ·· ···· • · · · • · · · • · • · · · * · · · «· · • · · · · · • · · • · • · • · · · · · ·· • · · ·

ORF amplification by PCR (Current Protocols in Molecular Biology, John Wiley &amp; Sons, Inc., F. Ausubel et al., ed.,

1994). For the preparation of H. pylori genomic DNA, see Example 1. The PCR reaction was performed by placing 10 ng of genomic HpJ99 DNA in a reaction vessel containing 10 mM Tris pH 8.3, 50 mM KCl, 2 mM MgCl ₂ , 2 micromolar synthetic oligonucleotide / primers ( encoding = Fl and reverse = R1), 0.2 mM each deoxynucleotide triphosphate (dATP, dGTP, dCTP, dTTP) and 1.25 units of thermostable DNA polymerase (AmplirtaqT ^- Roche Molecular ^- Systems Inc., Branchburg, NJ, USA) in a final volume of 40 μΐ. PCR was performed using a Perkin Elmer Cetus / GeneAmp PCR System 9600 to perform temperature cycles.

Upon completion of the temperature cycles, each sample of amplified DNA is visualized on a 2% ethidium bromide stained TAE agarose gel (Current Protocols in Molecular Biology, John Wiley &amp; Sons, Inc., F. Ausubel et al., 1994) to determine whether in the reaction the only product of the expected size was produced. The amplified DNA is then washed and purified using a Qiaquick Spin PCR purification kit (Qiagen, Gaithersburg, MD, USA).

PCR products were cloned into the pT7Blue T-vector (Catalog No. 69820-1, Novagen, Inc., Madison, WI, USA) using a TA cloning strategy (Current Protocols in Molecular Biology, John Wiley and Sons, Inc., F.). Ausubel et al., Eds., 1994). Ligation of the PCR product into the vector is performed by mixing a 6-fold molar excess of PCR product, 10 ng of pT7Blue-T vector (Novagen), 1 μΐ of T4DNA ligase buffer (New England Biolabs, Beverly, MA, USA) and 200 units of T4 DNA ligase (New). England Biolabs) in a final reaction volume of 10 μΐ. The ligation is carried out for 16 hours at 16 ° C.

The ligation products are electroporated (Current Protocols in

0 0 0 0 0 0

000 000

125 • 00 • * 0 0 0 0 0

0 0 0 0

0000000 00 0 • 3 ·· «·

Molecular Biology, John Wiley and Sons, Inc., F., Ausubel et al., 1994) to competent cells for the electroporation of XL-1 Blue or DH5- _r and E. coli (Clontech Lab.lne. , Palo Alto, CA, USA).

Briefly, 1 μΐ of the ligation reaction mixture is mixed with> 40 µg • electrocompetent cells and a high voltage pulse (25 µΡ, 2.5 kV, 200 Ω) is performed, after which the samples are incubated in 0.4.5 ml SOC. media (0.5% yeast extract, 2.0% trypton, 10: mM NaCl, 2.5 mM KCl, 10 mM MgCl ₂ , 10 mM MgSO ₄ and 20 mM glucose) at 37 ° C

Shaking for 1 hour. The samples are then propagated to —LB— (10 -------- g / l bacto trypton, 5 g / l bacto yeast extract, 10 g / l sodium chloride) plates containing 100 μg / ml ampicillin, 0.3 % X-gal and 100 µg / ml IPTG. These plates are incubated overnight at 37 ° C.

Ampicillin-resistant colonies are selected, cultured in 5 ml of liquid LB containing 100 µg / ml ampicillin, and plasmid DNA isolated using the Qiagen miniprep protocol (Qiagen, Gaithersburg, MD, USA). ··

To verify correct cloning of H. pylori DNA inserts, these pT7Blu plasmid DNAs were used as templates for PCR &apos; amplification of the cloned inserts, using the same coding and reverse primers as used for the initial amplification of the H. pylori J99 sequence. The determination of the appropriate primer and PCR product by visualizing on 2% TAE, an ethidium bromide stained agarose gel, confirms that the correct inserts have been cloned. Two to six clones thus tested are obtained for each knocked out target gene and frozen and stored at -70 ° C. To minimize PCR errors, plasmid DNAs are removed from these verified clones and used in subsequent cloning steps.

The gene / ORF sequences are reused to develop a second pair of primers that surround the H. pylori DNA region to be interrupted or deleted (up to 250 base pairs) in the ORF, but are

126 ί

ΦΦ φ * φφφφ

Orient · ovány ovány ovány ovány ovány ovány ovány ovány ovány ovány ovány ovány ovány ovány ovány ovány ovány ovány ovány ovány ovány ovány ovány ovány ovány ovány ovány ovány ovány ovány ovány ovány ovány ovány ovány ovány ovány ovány ovány. Circular plasmid DNA sets of previously isolated clones are used as templates for this round, PCR. Because it is the amplification orientation of this pair of deletion primers. on the contrary, a portion of the ORF between the two primers is not contained in the resulting PCR product: The product is linear DNA, with H. pylori DNA at each end and a pT7Blue vector between them, resulting in the deletion of the portion. ORF. The PCR product is visualized on &gt; 2% TAE, an ethidium bromide-stained agarose gel to determine if a single expected size product was amplified. ----------------- Kanamycin resistance cassette (Labigne-Rousell et al., 1988

J. Bacteriology 170: 1704-1708) is ligated into this PCR product by the TA cloning method used above (Current Protocols in Molecular Biology, John Wiley and Sons, Inc., F. Ausubel et al., Ed., 1994). A kanamycin cassette containing the Campzlobacter kanamycin resistance gene is obtained by digesting the plasmid pCTB8: kan (Cover et al., 1994, J. Biological Chemistry 269: 10566-10573) with EcoRI. The correct fragment (1.4 kb) was isolated on a 1% TAE gel and using a QIAquick gel extraction kit (Qiagen, Gaithersburg, MD, USA). The end of the fragment is repaired using the Klenow fill-in protocol, which comprises mixing 4 µg DNA fragment, 1 µΐ dATP, dGTP, dCTP, dTTP at a concentration of 0.5 M, 2 µΐ Klenow buffer (New England Biolabs) and 5 units of Klenow DNA Polymerase I Large (Klenow) Fragment (New England Biolabs) into a 20 μΐ reaction mixture, incubated at 30 ° C for 15 minutes and inactivated enzyme by heating to 75 ° C for 10 minutes. This blunt-ended kanamycin cassette is then purified using a Quiaquick column (Qiagen, Gaithersburg, MD, USA) to remove nucleotides. The T trap is then formed by mixing 5 µg of a blunt-ended kanamycin cassette, 10 mM Tris pH 8.3, 50 mM KCl, 2 mM MgCl, 5 units of DNA polymerase (Amplitaq, Roche Molecular Systems, Inc., Branchburg, NJ, USA). 20 μΐ 5 mM dTTP in 100 μΐ reaction mixture and incubation at 37 ° C for 2 hours. Kan-T

The 127 cassette is then purified using a Quiaquick column (Qiagen, Gaithersburg, MD, USA). The PCR product of deletion primers (F2 and R2) is ligated into the Kan-T cassette by mixing 10-25 ng of the deletion primer PCR product, 50-75 ng of Kan-T DNA cassette, 1 μΙΙΟχ T4 DNA ligase reaction mixture, 0.5 μ4 T4 DNA ligase (New.England Biolabs, Beverly, MA? USA) in 10 μΐ reaction mixture and incubate for 16 hours at 16 ° C.

The products were transferred to XL-1 Blue or DH5-α by electroporation as described above. After recovery in SOC, cells are plated on LB plates containing 10 gg / ml ampicillin and cultured overnight at 37 ° C. The plates were then replated on 25 µg / ml kanamycin plates and cultured overnight. The resulting colonies have both the ampicillin resistance gene present in the pT7 Blue vector and the newly inserted kanamycin resistance gene. Colonies are transferred to LB containing 25 µg / ml kanamycin and plasmid DNA isolated from cultured cells using the Qiagen miniprep protocol (Qiagen, Gaithersburg, MD, USA).

Several assays are performed by PCR amplification on these plasmids to verify that the kanamycin cassette is inserted in the H. pylori / ORF gene and to determine the orientation of the kanamycin resistance gene insert relative to the H. pylori gene / ORF. To verify that the kanamycin cassette is inserted into the H. pylori sequence, plasmid DNA is used as templates for PCR amplification with a set of primers originally used for cloning the H. pylori gene / ORF. The correct PCR product has the size of the deleted gene / ORF increased by a 1.4 kb kanamycin cassette. To avoid the potential polar effects of the kanamycin resistance cassette on the expression of the H. pylori gene, the orientation of the kanamycin resistance gene with respect to the knocked out gene / ORF is determined and both orientations are used in the transformation of H. pylori (see below). To determine the orientation of the insertion of the kanamycin resistance gene,

128 primers from the end of the kanamycin resistance gene (Kan-1

5'-ATCTTACCTATCACCTCAAAT-3 '(SEQ ID NO: 207)) and (Kan-2)

5 '-AGACAGCAACATCTTTGTGAA-3' (SEQ ID NO: 208)). Using each of the cloning primers together with each Kan primer (4 primer combinations), the orientation of the kanamycin cassette relative to the H. pylori sequence is determined. Positive clones are classified as either an A orientation (the same transcription direction is present for both the H. pylori gene and the ria kanamycin resistance gene) or as a B orientation (the transcription direction for the H. pylori gene opposite to the kanamycin resistance gene). Clones having the same orientation (A or B) were obtained for further experiments and independently transformed into H. pylori.

Transformation of plasmid DNA into H. pylori cells

Two H. pylori strains are used for transformation: ATCC 55679, a clinical isolate that provides / DNA from which the H. pylori sequence database is obtained, and AH244, an isolate that has been passaged in the mouse stomach and has the ability to colonize the mouse stomach. Cells for transformation are cultured at 37 ° C, 10% CO ₂ , 100% humidity, either on Sheep-Blood agar plates or on liquid Brucella Broth. Cells are cultured to the exponential phase and examined under a microscope to determine whether they are healthy (actively moving) and uncontaminated. For plate culture, cells are obtained by scraping cells from the plate using a sterile loop, suspended in 1 ml Brucella Broth, centrifuged (1 minute, maximum eppendorf microfusion speed) and resuspended in 200 μΐ Brucella Broth. When cultured in liquid Brucella Broth, cells are centrifuged (15 minutes at 3000 rpm on a Beckman TJ6 centrifuge) and the cell pellet is resuspended in 200 μΐ Brucella Broth. An aliquot of the cells is taken to determine the optical density at 600 nm to calculate the cell concentration. An aliquot (1 to 5 OD _goo units / 25 μΐ) resuspended

129 • ·

The cells were plated on a pre-warmed Sheep-Blood agar plate and incubated at 37 ° C, 6% CO ₂ , 100% humidity for 4 hours. After this incubation, 10 μΐ plasmid DNA (100 gg / ml) was placed on these cells. In parallel, a positive control (plasmid DNA with a ribonuclease H gene disrupted by the kanamycin resistance gene) and a negative control (without plasmid DNA) were performed. The plates were again incubated at 37 ° C, 6% CO ₂ , 100% humidity for 4 hours. Cells are then propagated on this plate using a brush soaked in Brucella broth and cultured at 37 °, 6%

CO ₂ for 20 hours. Cells are then transferred to Sheep-Blood agar plates containing 25 µg / ml kanamycin and cultured for 3-5 days at 37 ° C, 6% CO ₂ , 100% humidity. If colonies appear, they are harvested and re-cultured as bands on fresh plate containing Sheep-Blood agar containing 25 gg / ml kanamycin.

Three sets of PCR assays were performed to verify that transformant colonies were formed as a result of homologous recombination at the correct chromosome site. A template for PCR (colony DNA) is obtained by rapidly heating the DNA as follows. An aliquot of the colony (looping) is placed in 100 μΐ of 1% Triton X-100, 20 mM Tris, pH 8.5 and boiled for 6 minutes. An equal volume of phenol: chloroform (1: 1) was added and thorough mixing was performed. The mixture is microfused for 5 minutes and the supernatant is used as a DNA template for PCR with a combination of the following primers to verify homologous recombination at the correct chromosome site.

TEST 1. PCR with cloning primers originally used for gene / ORF amplification. A positive homologous recombination result at the correct chromosome site should be represented as a single PCR product, the size of which will be the size of the deleted gene / ORF increased by 1.4 kb of the kanamycin cassette. A gene size / ORF PCR product means that the gene has not been knocked out and that the transformant has not

130 · · · v v v v v ¹ 1 1 1 1 1 1 1 1 1

as a result of homologous recombination at the correct chromosome site.

TEST 2. PCR with F3 (primer designed for sequence upstream of gene / ORF and absent on plasmid) and either 'Kan-1 or Kan-2 primer (primers designed from gene ends; kanamycin resistance)', depending on whether used The DNA was an A or B orientation.

Homologous recombination at the correct chromosome site will result in a single PCR product of the expected size (i.e., from F3 to the site of the kanamycin resistance gene). No PCR product or PCR product of the wrong size means that the plasmid has not been integrated at the correct site and that the gene has not been knocked out.

-TEST 3. PCR with R3 (primer designed for the sequence downstream of the gene / ORF and absent from the plasmid) and either Kan-1 or Kan-2 primer, depending on whether the DNA used was an A or B orientation. Homologous recombination at the correct chromosome site will result in '. formation of a single PCR product of the expected size, (i.e. from the insertion site of the kanamycin resistance gene to the downstream location of R3). Again, no PCR product or PCR product of the wrong size means that the plasmid has not been integrated at the correct site and that the gene has not been knocked out.

Transformants having positive results for all three assays listed above show that the gene is not essential for in vitro survival.

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

In case no colony results from two independent transformations, although a positive control with a broken plasmid DNA for ribonuclease H produces transformants, the plasmid DNA is

131

further analyzed by PCR on DNA from a transformant population prior to placement on colony forming plates. In this way, it is verified that the plasmid can enter cells and undergo homologous recombination at the right site. Briefly, plasmid DNA is incubated according to the transformation protocol above. DNA is extracted from H. pylori cells immediately after incubation with the plasmid DNA and the DNA is used as a template for TEST 2a and TEST 3 above. Positive results in Test 2 and Test 3 confirm that the plasmid DNA can enter cells and undergo homologous recombination in the right place of the chromosome. If TEST 2 and TEST 3 are positive, the inability to obtain viable transformants indicates that the gene is essential and that cells disrupting this gene are incapable of forming colonies.

VII. High performance drug search tests

Protein cloning, expression and purification

The cloning, transformation, expression and purification of the target H. pylori gene and its protein product, for example the H. pylori enzyme, which is used in the high throughput drug screening assay, is performed as described in Examples 2 and 3, supra. The 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.

Enzyme test

The assay is performed as described by Fisher (Fisher, G. et al., (1984) Biomed. Biochim. Acta 43: 1101-1111). The assay measures the cis-trans isomerization of Ala-Pro binding in the N-succinyl-Ala-Ala-Pro-Phe-p-nitroanilide test peptide (Sigma # S-7388, lot # 84H5805). Α-chymotrypsin is used in the test and has an ability of 9 9 · 9 · 9 · 9 · 9 · 9

9 99 9

-1 η -) · 9 · 9 · 9 · 9 ···

JZ 99 9 9 * 9 9 cleavage of the test peptide only occurs when the Ala-Pro binding is in trans form. The conversion of the test peptide to the'-trans isomer is monitored at 390 nm on the Beckman Model, DU-650 spectrophotometer, data are obtained every second with an average reading time of 0.5 s. The tests are performed with .35 mM HEPES, pH 8.0 in a final volume of 400 μΐ, with 10 μΜ α-chymotrypsin (type 1-5 bovine pancreas, Sigma No C-7762, lot 23H7020) and 10 nM PPIase. To initiate the reaction, 10 μΐ of substrate (2 mM N-succinyl-Ala-Ala-Pro-Phe-p-nitroaniTidu in DMSO) is added to 390 μΐ reaction ^- mixture at room teplotě.Enzymový assay in crude bacterial extract ml culture of H. pylori (strain J99) in Brucella broth is collected in mid-log phase (0D _soo approximately 1) and resusped in lysis buffer with the following protease inhibitors: 1 mM PMSF and 10 gg / ml each of leupeptin, aprine, pepstatin, TLCK, TPCK and soybean trypsin inhibitor. The suspension is subjected to three freeze-thaw cycles (15 minutes at -70 ° C, then 30 minutes at room temperature), then sonication (30 s shock). The lysate is centrifuged (12,000 xg for 30 minutes) and the supernatant is assayed for enzymatic activity as described above.

Many H. pylori enzymes can be expressed at high concentrations and in active form in E. coli. Such large amounts of purified proteins are suitable for the development of various high throughput drug screening assays.

Equivalents

Those skilled in the art will be able to create many equivalents to the individual embodiments and methods described herein. Such equivalents fall within the scope of the appended claims.

• «· · · · ·« «* * * *

Sequence list

- (1) General information:

(i) Applicant:

(A) Name: Astra Aktiebolag (B) Street: S-15185 (C) City: Sodertalje (D) Country:

(E) Country: Sweden (F) Postal Code (ZIP) (ii) Title of the invention: Nucleic acid and amino acid sequences related to Helicobacter pylori and vaccine. means (iii) Number of sequences: 208 (iv) Computer read form:

(A) Media type:

(B) Computer:

(C) Operating system:

(D) Software:

(v) Details of the current application:

(A) Application Number:

(B) Filing Date:

(vi) Previous application dates:

(A) Application Number: US 08/739150 (B) Filed: 28/10/1996 (vii) Previous Application Date:

·· ····

134 ·· · • · (A) Application No.: US 08/759739 (B) Filing Date: 12/6/1996 A (viii) 'Previous Application Date:', (A). Application Number: US 08/891928 (B) ) Filing date: 14/07/1997 (ix) Mailing Address (A) Address: Lahive & Cockfie1d (B) Street: 28 State Street (C) City: Boston (D) Country: Massachusetts (E) Country: USA (F) ZIP: 02109-1875 (x) Agent / Agent Information (A) Name: Mandragouras, Amy E.

(B) Registration number: 36207 (C) Reference / Registry number: GTN-001CP10PC (ix) Telecommunication information:

(A) Phone: (617)227-7400 (B) Fax: (617)742-4214 (2) Information for SEQ ID NO: 1:

(i) Sequence characteristics:

(A) Length: 561 base pairs (B) Type: nucleic acid (C) String: double (D) Topology: circular (ii) Molecule type: DNA (genomic) (iii) Hypothetical: NO

135

(iv) Antisense: NO (vi) Original Source:

(A) Organism: Helicobacter pylori (ix) Features :. (A) Name / Key: misc_character (B) 'Location: 1 ... 561 (xi) Sequence Description: SEQ ID NO: 1:

ATGATTAAAA GAATTGCTTG TATTTTAAGC TTGAGCGCGA GTTTAGCGTT AGCTGGCGAA 60

GTGAATGGGTTTTTCATGGGTGCGGGTTATCAACAAGGTCGTTATGGCCCTTATAACAGC - 120

AATTACTCTG ATTGGCGTCA TGGCAATGAC CTTTATGGTT TGAATTTCAA ATTAGGTTTT 180

GTAGGCTTTG CCAATAAATG GTTTGGGGCT AGGGTGTATG GCTTTTTAGA TTGGTTTAAC 240

ACTTCAGGGA CTGAACACAC CAAAACCAAT TTGCTCACCT ATGGCGGCGG TGGCGATTTG 300

ATTGTCAATCTCATTCCTTT GGATAAATTC GCTCTAGGTC TCATTGGTGG CGTTCAATTA 360

GCCGGAAACA CTTGGATGTT CCCTTATGAT GTCAATCAAA CCAGATTCCA GTTCTTATGG 420

AATTTAGGCG GAAGAATGCG TGTTGGGGAT CGCAGTGCGT TTGAAGCGGG CGTGAAATTC 480

CCTATGGTTA ATCAGGGTAG CAAAGATGTA GGGCTTATCC GCTACTATTC TTGGTATGTG 54 0

GATTATGTCT TCACTTTCTA G 561 (2) Information for SEQ ID NO: 2 .:

(i) Sequence characteristics:

(A) Length: 351 bp (B) Type: nucleic acid (C) String: double (D) Topology: circular (ii) Molecule type: DNA (genomic) (iii) Hypothetical: NO (iv) Antisense: NO ( (vi) Original source:

(A) Organism: Helicobacter pylori (ix)

(A) Name / Key: misc_charakter (B) Location: 1 ... 351

136 φφ φφφφ 'φ φ (xi) Sequence description: SEQ ID NO: 2:

TTGATGCGCA TTATCATAAG GTTACTTTCA TTTAAAATGA‘ACGCTTTTTT · AAAACTCGCG 60. ·; ctcgcttctt tgatgggggg GCTTTGGTAT GCTTTCAATG .GCGAAGGCTC ‘TGAGATTGTC 12 o. GCTATAGGGA · 'TTTTTGTGTT GATCTTGTTT GTTTTTTTTAUTCCGCCCTGT.GAGTTTCCAA 180

GACCCAGAAA AACGAGAAGA ATACATAGAA CGGCTTAAAA '. AAAACCATGAti GAGGAAAATG 24 0 ATCTTACAAG ACAAGCAAAA AGAAGAGCAA ATGCGCCTCT ATCAAGCCAA / AAAAGAGCGA 3 00

(i) Sequence characteristics:

(A) Length: 1038 base pairs (B) Type: nucleic acid (C) String: double (D) Topology: circular (ii) Molecule type: DNA (genomic) (iii) Hypothetical: NO (iv) Antisense: NO ( (vi) Original source: '(A) Organism: Helicobacter pylori' (ix) Properties:

(A) Name / Key: misc_charakter (B) Location: 1 ... 1038 (xi) Description of Sequence: SEQ ID NO: 3:

ATGGTTAAAC ACTATCTTTT CATGGCGGTT TCGCAGGTCT TTTTCTCCTT CTTTTTAGTG 60 CTGTTTTTTA TCTCTTCCAT TGTGTTATTA ATCAGTATTG CAAGCGTAAC GCTCGTGATT 120 AAAGTGAGCT TTTTGGATCT GGTGCAACTC TTTTTGTATT CCTTGCCAGG AACCATTTTT 180 TTTATTTTGC CGATCACTTT TTTTGCGGCT TGCGCTTTGG GGCTTTCAAG GCTTAGCTAT 24 0 GACCATGAAT TGTTAGTGTT TTTCTCTTTA GGGGTTTCGC CTAAAAAAAT GACTAAAGCG 300 TTTGTGCCTT TAAGTTTGTT AGTGAGCGCG ATTTTATTAG CGTTTTCGCT CATCTTAATC 360 CCCACTTCTA AGAGCGCTTA TTACGGGTTT TTGCGTCAAA AAAAAGACAA GATTGACATT 420 AACATCAGAG CGGGTGAATT CGGGCAAAAA TTAGGCGATT GGCTCGTGTA TGTGGATAAG 480 ACTGAAAACA ATTCCTATGA TAATTTGGTG CTTTTTTCTA ATAAAAGTCT CTCTCAAGAA 540 AGCTTTATTT TGGCTCAAAA AGGCAATATC AACAATCAAA ACGGCGTGTT TGAATTGAAT 600 TTGTATAACG GGCATGCGTA TTTCACTCAA GGCGATAAAA TGCGTAAGGT TGATTTTGAA 660 GAATTGCATT TGCGCAACAA GCTCAAGTCT TTCAATTCTA ATGATGCGGC TTATTTGCAA 720 GGCACGGATT ATTTGGGTTA TTGGAAAAAA GCCTTTGGTA AAAACGCTAA TAAAAATCAA 780 AAACGCCGTT TTTCTCAAGC GATCTTAGTT TCCTTGTTCC CTTTAGCGAG CGTGTTTTTA 840 ATCCCCTTAT TTGGCATCG C CAACCCGCGA TTCAAAACGA ATTGGAGTTA TTTCTATGTC 900 CTTGGAGCGG TTGGGGTTTA TTTTTTAATG GTGCATGTGA. TTTCTACGGA TTTGTTTTTG 960 ATGACCTTTT TCTTCCCCTT TATTTGGGCG TTTATTTCTT ATTTATTGTT TAGAAAATTC 1020 ATTTTAAAGC GTTATTAA 1038

137

(2) Information for SEQ ID NO: 4:

(i) Sequence characteristics:

(A) Length: 831 base pairs (B) .Type:. Nucleic acid (C) String: double (D) Topology: circular (ii) Molecule type: DNA (genomic) (iii) Hypothetical: NO (iv) Antisense: NO (vi) Original source:

(A) Organism: Helicobacter pylori (ix)

(A) Name / Key: misc_charakter (B) Location: 1 ... 831 (xi) Description of Sequence: SEQ ID NO: 4:

ATGAAGAAAA AAGCAAAAGT CTTTTGGTGT TGTTTTAAAA TGATTCGTTG GTŤGTATTTG 60 GCGGTCTTTT TTTTGTTGAG CGTATCAGAC GCTAAAGAAA 'TCGCTATGCA. <ACGATTTGAC 120 AAACAAAACC ATAAGATTTT TGAAATCCTT GCGGATAAAG TGAGCGCCAA AGACAATGTG 180 ATAACCGCCT CAGGGAATGC GATCCTATTG AATTATGACG TGTATATTCT AGCGGATAAG 240 GTGCGTTATG ACACCAAGAC TAAAGAAGCG TTATTAGAAG GCAATATTAA GGTTTATAGG 300 GGCGAGGGCT TGCTCGTTAA AACCGATTAT GTGAAATTGA GTTTGAACGA AAAATATGAG 360 ATCATTTTCC CCTTTTATGT CCAAGACAGC GTGAGCGGGA TTTGGGTGAG CGCGGATATT 420 GCTAGCGGGA AGGATCAAAA ATATAAGATT AAAAACATGA GCGCTTCAGG GTGCAGCATT 480 GACAACCCCA TTTGGCATGT CAATGCGACT TCAGGCTCAT TTAACATGCA AAAATCGCAT 540 TTGTCAATGT GGAATCCTAA GATTTATGTC GGCGATATTC CTGTATTGTA TTTGCCCTAT 600 ATTTTCATGT CCACGAGCAA TAAAAGAACT ACCGGGTTTT TATACCCTGA GTTTGGCACT 660 TCCAACTTAG ACGGCTTTAT TTATTTGCAA CCCTTTTATT TAGCCCCCAA AAACTCATGG 720 GATATGACCT TTACCCCACA AATCCGTTAC AAAAGGGGTT TTGGCTTGAA TTTTGAAGCG 780 CGCTACATCA ACTCTAAGAC GCAGGTTTTT ATTCAATGCG CGCTATTTTA G 331 (2) Information for SEQ ID N O: 5:

(i) Sequence characteristics:

(A) Length: 675 bp (B) Type: nucleic acid (C) String: double (D) Topology: circular (ii) Molecule type: DNA (genomic) (iii) Hypothetical: NO (iv) Antisense: NO

· '·

138

(vi), Original Source:

- (A) Organism: Helicobacter pylori (ix) (Features:

. (A), Name / Key: misc_chařakter, 7 (B) Location: l. .675 (xi) -Description of sequence: SEQ ID NO: 5:

. ATGATTAGAT 'TAAAAGGTTT - GAATAAAACT TTAAAAACAA GCTTATTAGC TGGGGTTTTA CTAGGTGCTA-CTGCTCCCTT AATGGCAAAG CCTTTATTAA GCGATGAAGA CTTATTGAAA GGCTCTCAAT ACTTGAATAG TGGTTGGAAT TTATCTAAAGAATTTCCGCA AGAATATAGA GAAAAGATŤT TTGAATGCGT AGAAGAAGAA AAACATAAAC AAGCCCTTAA TTTAATCAAT AAAGAAGACA CTAAAGATAA AGAAGAACTT GCAAAAAAAA TCAAAGAAATTAAAGAAAAA GCTAAAGTTT taaggcaaaa atttatggct tttgaaatga aagaacactc taaagaattc CCAAATAAAA AGCAACTTCA AACCATGCTT GAGAACGCTT TTGATAATGG ..AGCTGAAAGT TTTATTGATG ATTGGCACGA ACGCTTTGGG GGTATAAGTA GAGAGAATAC TTATAAAGCA CTTGGCATTA AAGAATATAG TGATGAAGGA AAGATATTGC CTTTGGCGAA AGAAGTTATA TTAGACAATA TAAAAAAGAT TTTGAAGAAA GCACTTATGA TACTAGACAA CCCTTATCTG CTATGGCTAG Tatge

120 1.8 0 240 300 360 420 430 540 600 660 675 (2) Information for SEQ ID NO: 6:

(i) Sequence characteristics:

(A) Length: 1290 bp (B) Type: nucleic acid (C) String: double (D) Topology: circular (ii) Molecule type: DNA (genomic) (iii) Hypothetical: NO (iv) Antisense: NO ( (vi) Original source:

(A) Organism: Helicobacter pylori (ix)

(A) Name / Key: misc_charakter (B) Location: 1 ... 1290 (xi) Description of Sequence: SEQ ID NO: 6:

 ·· ···········

139

ATGCCATACG CCTTAAGAAA AAGATTTTTC AAACGCCTTT TATTGTTTTT TTTAATTGTT 60

TGTATGATAA ATTTGCATGC CAAAAGCTAT CTGTTTTCTC CTTTGCCCCC AGCGCACCAG 120

CAAATCATTA AGACAGAGCC TTGCTCTTTG GAGTGCTTGA AAGACTTGAT GCTGCAAAAT 180

CAAATCTTTT CTTTTGTATC CCAATACGAT GATAACAACC AAGATGAGAG CCTTAAAACT 240

TATTACAAGG ACATCTTAAA CAAACTCAAC CCCGTATTCA TCGCTTCTCA AACTCCAGCT 300

AAAGAAAGCT ATGAGCCTAA GATTGAATTA GCGATTTTAC TGCCTAAAAA GGTGGTGGGC 360

CGTTATGCGA .TTTTAGTGAT GAACACCCTT TTAGCGTATT TGAACACCAG AAACAACGAT 420: TTCAATATCC AAGTCTTTGA CAGCGATGAA-GAAAGCCCTG / AAAAATTAGA -AGAAACCTAT 480

AAAGAAATTG 'AAAAAGAAAA ATT.CCCTTTT ATCATCGCTT -TATTGACTAA AGAGGGCGTG 540

GAAAATTTGC. TCCAAAATAC GACTATCAAT ACCCCTACTT ATGTGCCTAC .'GGTGAATAAA 600

ACGCAATTAG 'AAAATCATAC CGAGCTTTCT TTAAGCGAGC GCTTGTATTTTGGGGGGATT 660 GATTATAAAG AGCAATTAGG CATGCTCGCA ACTTTCATTA .GCCCTAATTC - GCCCGTGATT 720'

GAATACGATG ATGATGGCCT3GATAGGTGAA CGCTTGAGGC AAATCACGGA-GTCTTTAAAC 780

GTTGAAGTCA AACACCAAGA AAACATTTCT · TACAAACAAG. CGACCAGTTT 'TTCTAAAAAT 840': TTTAGAAAAC, ATGATGCGTT TTTTAAAAAT TCTACCTTAA '.TTTTGAACAC CCCTACCACT 900

AAAAGCGGTC TGATCCTTTC TCAAATAGGG ČTTTTAGAGT''ATAAGCCTCT '.TAAAATCCTT 960

TCCACACAAA TCAATTTCAA CCCCTCTTTA CTCTTGCTCA CCCAGCCTAA AGACAGGAAA 1020 _AATTTATTCA TTGTCAATGC CTTGCAAAAC AGCGATGAAA CGCTGATAGA ATACGCTTCC 1080

TTATTAGAGA GCGATTTAAG GCATGATTGG GTGAATTATT CCAGCGCGAT AGGGTAGAG 1140

ATGTTTTTAA ACACGCTAGA TCCGCATTTT AAAAAGTCTT TTCAAGAGAG TTTGGAAGAC 1200

AATCAAGTCC GTTACCACAA TCAAATTTAT CAGGCTTTAG. .GGTATTCTTT TGAGCCGATA 1260

AAAAACGAAA GCGAAACAAA AAAAGAATAA ¹²⁹⁰ (2j Information for SEQ ID NO: 7:

(i) Sequence characteristics:

(A) Length: 1368 pairs (B) Type: nucleic acid (C) String: double (D) Topology: circular '(ii) Molecule type: DNA (genomic) (iii) Hypothetical: NO (iv) Antisense: NO (vi) Original source:

(A) Organism: Helicobacter pylori (ix)

(A) Name / Key: misc_charakter (B) Location: 1 ... 1368 (xi) Description of Sequence: SEQ ID NO: 7:

GTGTTAAAAT.

TTATTGGCTT

AACCATTCCA

ACGATCAAGC

AAAATAGGCG

GACCAAGCCA

GGGTTTTTAG

AATTATGTGC

TTAGGGCGTT

GATTATAAAA

TTCAAAAATT

TTGATTATAA

AACTCAATTC

TTCAAGTGGA

TTGGGGGGAT

CGCATCAAAT

GCAACGCTCC

TGTATAAŤTC atctctctaa

TCAATTCTAA

ACCCTTATTG

GTTTAGTGGG

CAAAGAAGGG

TTCCAATCTG

TTTAGGAGCG

CTATGGCTCA

TTGGAAAGAC

CTATCTGTTT

CATGGATTTT

AATAGCGTTA

TTTGTTTCCA

GTAGCGGAAT

ATTTTCCCTA

CTCCCTAAAA

CTCGCTTACG

GAACTTTTTT

TCCCTCATAG

TATTCTTATG

ATGAGTTCCT

AAATGGTTTA

TTCTTTATAA

CTGTTTCTAA

CAGCCACCTT

ACATTGAAAA

ATTCCACCAA

ACCTCATAGG

AATCTGACGC

GCGATAAATT

ACACACAGGG

GCTCTTTTGG

TCAAAGCCCT 60 AGTGGGGTTT 120 TGTAACCGCC 180 ACACAGCTTA 240 AACGCTCATA 300 GCGTTGGTGG 360 TCACACCCGT 420 CCACCTAAAA 480 TTTTGAACTG 540 GAGGGCGTTG 600

140

GCTTTTGGGC AATGGATACG GGATTGGTAT GCCCCTATTG TAACTGAAGA TGGCAGAAAA 660 GAAGTTTATG ATGGCATCCA TGCCGCGCAA CTCTATTTTT CTAGCAAGCA TGTTCAAGTC 720 ATGCCTTTTG CTTATTTTTC GCCTAAGATT TACGGAGCGC CCGGTGTTAA AATCCATATT 780 GATAGCAACC CGAAATTCAA AGGCTTAGGG TTAAGGGCTC AAACCACTAT TAATGTGATT 840 TTCCCTGTTT ATGCTAAAGA TTTATACGAT GTGTATTGGC GTAACTCTAA GATTGGCGAG 900 TGGGGCGCAT CGCTTTTGAT CCACCAACGC TTTGACTACA ACGAATŤTAA CTTTGGCTTT 960 GGTTATTACC AAAATTTTGG CAACGCTAAC GCAAGGATTG GCTGGTATGG TAACCCCATC 1020 CCTTTTAATT ATAGAAATAA CAGCGTTTAT GGTGGGGTCT'TCAGTAACGC TATTACCGCA 1080 GACGCCGTTT CTGGGTATGT CTTTGGTGGG GGGGTGTATA GAGGGTTTTT ATGGGGTATT 1140 TTAGGCAGAT ACACTTATGC CACTAGAGCG AGCGAAAGAT CCATCAACTT GAACTTGGGC 1200 TATAAATGGG GTTCTTTTGC TAGAGTTGAT GTGAATTTAG AATACTATGT GGTCAGCATG 1260 CACAAGGGGT ATAGATTAGA CTATCTCACC GGCCCTTTCA ÁCAAAGCCTT TAAGGCTGAC 1320 • GCACAAGATA GGAGTAACCT TATGGTTAGC ATGAAATTČT'ŤTTTTTAA ^136E (2) Information for SEQ ID NO: 8:

(i) Sequence characteristics:

(A) Length: 849 bp (B) Type: nucleic acid (C) String: double (D) Topology: circular (ii) Molecule type: DNA (genomic) '(iii) Hypothetical: NO (iv) Antisense: NO (vi) Original source:

(A) Organism: Helicobacter pylori (ix)

(A) Name / Key: misc_charakter (B) Location: 1 ... 849 (xi) Sequence Description: SEQ ID NO: 8:

ATGGGGTGTT CGTTTATCTT TAAAAAAGTT AGGGTTTATT CTAAAATGTT GGTTGCTTTG 60 GGGCTTTCAA GCGTGTTGAT CGGTTGCGCG ATGAATCCAA GCGCTGAGAC AAAAAAACCA 120 AATGACGCCA AAAACCAACA ACCAGTTCAA ACTCATGAAA GAATGACAAC AAGTTCTGAA 180 CATGTTACGC CACTAGATTT TAATTACCCG GTGCATATTG TTCAAGCCCC ACAAAACCAT 240 CATGTTGTAG GTATTTTAAT GCCACGCATT CAAGTGAGCG ATAATCTAAA ACCCTATATT 300 GATAAGTTTC AAGACGCTTT AATTAATCAA ATCCAAACTA TTTTTGAAAA AAGAGGCTAT 360 CAAGTGTTGC GTTTTCAAGA TGAAAAAGCT TTGAATGTGC AAGATAAGAA AAAGATTTTT 420 TCCGTTTTGG ATTTGAAAGG GTGGGTAGGA ATCTTAGAAG ATTTGAAAAT GAATTTAAAA 480 GATCCCAATA GTCCCAATTT AGACACGCTA GTGGATCAAA GCTCAGGCTC TGTATGGTTT 540 AATTTTTATG AACCAGAAAG CAATCGTGTC GTCCATGATT TTGCTGTAGA AGTAGGAACT 600 TTTCAGGCAA TAACATACAC ATACACCTCT ACTAATAACG CTTCAGGAGG GTTTAATTCT 660 TCAAAAAGCG TTATCCATGA AAATTTGGAT AAGAATAGAG AAGACGCGAT ACACAAGATT 720 TTAAACAGAA TGTATGCGGT TGTCATGAAA AAAGCTGTAA CAGAACTTAC AAAAGAAAAT 780 ATCGCCAAAT ACAGAGACGC TATTGATAGA ATGAAAGGCT TTAAAAGTTC TATGCCTCAA 840 AAAAAGTAG 849

141 · ·

449 · ··, '' · · ''^; · 1 · · · · · · · · (2) · Information for SEQ ID NO: 9:

(i) Sequence characteristics: (A) Length: 843 pairs (b) Type: nucleic acid (C) String: double • (D) Topology: circular (ii) Molecule type: DNA (genomic) (iii) Hypothetical : NO (iv) Antisense: NO (vi) Original Source:

(A) Organism: Helicobacter pylori (ix)

(A) Name / Key: misc_character (B) Location: 1 ... 843. (Xi) Sequence description: SEQ ID NO: ^ 9: '

ATGAAACTGA GAGCAAGTGT TTTAATCGGT GTGGCAÁTTC TGTGCTTAAT TTTAAGTGCG 60 TGCAGTAACT ATGCGAAAAA AGTGGTGAAA CAAAAGAACC ATGTTTATAC GCCTGTGTAT 120 AATGAACTGA TAGAGAAGTA TAGTGAGATC CCCTTAAATG ACAAACTCAA AGACACACCA 180 TTCATGGTGC AAGTGAAGTT GCCAAATTAC AAGGACTATT TGTTGGATAA TAAACAAGTT 24 0 GTACTAACTT TCAAACTTGT TCACCATTCT AAAAAGATTA CGCTCATAGG CGATGCCAAT 300 AAGATCCTCC AATACAAGAA TTACTTCCAA GCTAACGGGG CAAGATCTGA CATTGATTTT 360 TACTTGCAAC CCACTTTGAA TCAAAAGGGT GTGGTGATGA TAGCGAGTAA CTACAATGAT 420 AATCCCAACA ACAAAGAAAA ACCACAGACC TTTGATGTGT TGCAAGGAAG TCAGCCAATG 480 CTAGGAGCTA ACACAAAAAA CTTGCATGGC TATGATGTGA GTGGAGCAAA CAACAAGCAA 540 GTGATCAATG AAGTGGCAAG AGAAAAAGCT CAGCTAGAAA AAATCAATCA GTATTACAAG 600 ACTCTCTTGC AAGACAAGGA ACAAGAATAT ACCACTAGGA AAAATAACCA ACGAGAAATT 660 TTAGAAACAT TGAGTAATCG TGCAGGTTAT CAAATGAGGC AGAATGTGAT TAGTTCTGAG 720 ATTTTTAAGA ATGGCAACTT GAACATGCAA GCCAAAGAAG AAGAAGTTAG GGAGAAGCTA 780 CAAGAAGAAA GAGAGAATGA ATACTTGCGC AATCAAATCA GAAGTTTGCT CAGTGGTAAG 840 TGA 843 (2) Information ce for SEQ ID NO: 10:

(i) Sequence characteristics:

(A) Length: 1179 pairs of bases (B) Type: nucleic acid (C) String: double (D) Topology: circular ^; and*·

142

(ii) Molecule type (iii) Hypothetical (iv) Antisense

DNA (genomic)

NO (iv)

NO (vi) Original source:

(A) Organism: Helicobacter pylori. ...

>. 1 (ix) · Features:

(A) Name / key: misc_character.

(B) Location: 1 ... 1179 (xi) Sequence Description: SEQ ID NO: 10:

ATGAGAAAAC TATTCATCCC ACTTTTATTA TTCAGCGCTT .. TAGAAGCGAA CGAGAAAAAC 6 0 GGCTTTTTCA TAGAAGCCGG CTTTGAAACT GGGCTATTAG AAGGCACACA AACGCAAGAA 120 AAAAGACACA CCACCACAAA AAACACTTAC GCAACTTACA ATTATTTACC CACAGACACG 180 ATTTTAAAAA GAGCGGCTAA TTTATTCACC AATGCCGAAG CGATTTCAAA ATTAAAATTC 240 TCATCTTTAT CCCCTGTTAG AGTGTTGTAT ATGTATAATG GTCAATTAAC TATAGAAAAC 300 TTCTTGCCTT ATAATTTAAA TAATGTTAAG CTTAGTTTTA CAGACGCTCA AGGCAATGTG 360 ATCGATCTAG GCGTGATAGA GACTATCCCC AAACACTCTA AGATTGTTTT GCCCGGAGAG 420 GCATTTGATA GTCTAAAAAT TGACCCCTAT ACCTTTATTTC 'TTCTAAAAAT TGAAGCCACT 480 AGCACTTCTA TTTCTGACGC TAACACGCAG AGGGTGTTTG AAACGCTCAA TAAGATTAAG. 54 0 ACAAATTTGG TCGTAAATTA TAGGAATGAA AACAAATTTA AAGATCACGA AAATCATTGG 600 GAAGCCTTTA CCCCACAAAC CGCAGAAGAA TTCACTAATT TAATGTTGAA CATGATCGCT 660 GTTTTAGACT CCCAATCTTG GGGCGATGCG AŤCTTAAACG CTCCTTTTGA GTTCACTAAC 720 AGCCCAACAG ATTGCGATAA TGATCCTTCA AAATGCGTAA ATCCTGGGAC AAACGGGCTT 780 GTCAATTCTA AAGTCGATCA AAAATATGTG TTAAACAAAC AAGACATTGT CAATAAATTT 840 AAAAACAAAG CGGATCTTGA TGTAATTGTT TTAAAGGATT CAGGGGTTGT AGGGCTTGGG 900 AGTGATATTA CCCCTAGCAA CAATGATGAT GGCAAGCATT ATGGCCAGTT AGGGGTAGTA 960 GCTTCTGCTT TAGATCCTAA AAAACTCTTT GGCGATAACC TTAAGACTAT CAATTTAGAG 1020 GATTTAAGAA CCATCTTGCA TGAATTCAGC CACACTAAAG GCTATGGGCA TAACGGGAAT 1080 ATGACCTATC AAAGAGTGCC GGTAACGAAA GATGGTCAAG TGGAAAAGGA TAGTAATGGC 1140 AAGCCAAAAG ATTCTGATGG CCTCCCCTAT AATGTGTGT 1179 (2) Information for SEQ ID NO: 11:

(i) Sequence characteristics:

(A) Length: 813 pairs (b) Type: nucleic acid (C) String: double (D) Topology: circular (ii) Molecule type: DNA (genomic) (iii) Hypothetical: NO (iv) Antisense: NO

143 ··· · ···. · (Vi) Original source:

(A) Organism: Helicobacter pylori * (ix) Properties:

(A) Name / Key :, misc_character (B) Location: 1 ... 813 (xi) Sequence Description: SEQ ID NO: 11: '

ATGAAAAAGT TTGTAGC7TT AGGGCTTCTA TCCGCGGTTT-TAAGCTCTTC ^ GTTGTTAGCC GAAGGTGATG GTGTTTATAT AGGGACTAAT TATCAGCTTG 'GACAAGCCCG TTTGAATAGC AATATTTATA ATACAGGGGA TTGCACAGGG AGTGTTGTAG GTTGCCCCCC AGGTCTTACC GCTAATAAGC ~ ATAATGCAGG-AGGGAGCAAT-ATCAATTGGC-ACTCCAAATA_CG.CTAATGGG_ GCTTTGAATG GTTTTGGGTT GAATGTGGGT TATAAGAAAT TCTTCCAATT CAAGTCGCTA GATATGACAA GCAAGTGGTT TGGTTTTAGA GTGTATGGGC TTTTTGATTA CGGGCATGCC GATTTAGGTA AACAAGTTTA TGCACCTAAT AAAATCCAGT TGGATATGGT CTCTTGGGGT GTGGGGAGCG ATTTGTTAGC TGATATTATT GATAAAGACA ACGCTTCTTT TGGTATTTTT GGTGGGGTCG CTATCGGCGG TAACACTTGG AAAAGCTCTG CAGCAAACTA TTGGAAAGAG CAAATCATTG AAGCCAAAGG TCCTGATGTT TGTACCCCTA CTTATTGTAA CCCTAATGCC CCTTATAGCA CCAACACTTC AACCGTCGCT TTTCAAGTGT GGTTGAATTT TGGGGTGAGA GCCAATATCT ACAAGCATAA TGGCGTGGAA TTTGGCGTGA GAGTGCCGCT ACTCATCAAT AAATTTTTGA GCGCGGGTCC taacgctact aacctttatt accatttgaa ACGGGATTAT TCGCTTTATTTGGGGTATAA CTACACTTTT TAA (2) Information for SEQ ID NO: 12:

(i) Sequence characteristics:

(A) Length: 423 pairs (B) Type: nucleic acid (C) String: double (D) Topology: circular (ii) Molecule type: DNA (genomic) (iii) Hypothetical: NO (iv) Antisense: NO ( (vi) Original source:

(A) Organism: Helicobacter pylori (ix)

(A) Name / Key: misc_charakter (B) Location: 1 ... 423 (xi) Sequence Description: SEQ ID NO: 12:

120

180

240

300

360

420

480

540

600

660

720

780

813 '

144

SO

120

ISO

240

300

3S0

420

423 ·· 1? · «· ·· ··

I »· · · · · · · · · · · · · · · · · · · · ·

ATGCATCCTA

GGAACACTTT

GCAAAGAGTT

GAATTAATAG

GACATGAGAG

GAAATTGATT

ATAGAAAAAT

TAATGTTTGC CTATATCGCT AACGCGCTCG CTCAAGOTAG AAAGATCAAC GCATGGCGTT TCAAAAAATA TCTCAAGTCA AAGAATTAGG CATTGATAAA TGATAGGCAA CCTTTCTCAA GTGATTATCT ACCCCAGAAA AGATACTGAT AATGTGGCGT CCCATTAAGC GATAGTGAAA TCAATTTCTT ACACAACACG CCAGACAAGT GCTAGTAAAA AATATCGTTA CAAACGOTTC AGCTTTTATT TAAAAAAGAT TTGCAAGAAC TACTTTATAT TCTTGATAGC AATGCTGGTA CCTCAATGAT CTTAAAAAAG CAAACCAAGA AACTTATAAG GAAGAGTATT

TAA · (2) Information for SEQ ID NO: 13:

(and)

Sequence characteristics:

(A) Length: 771 bp (B) Type: nucleic acid (C) String: double

- (- Dj — Topology: Circular -------------- (n) Type of molecule: DNA (genomic) (iii) Hypothetical: NO (iv) Antisense: NO (vi) Original source:

(A) Organism: Helicobacter pylori (ix)

(A) Name / Key: misc_character (B) Location: 1 ... 771 '(xi) Sequence Description: SEQ ID NO: 13:

ATGTTGGGGA GCGTCAAAAA AGCGGTTTTT TGCGGGGGGT TAATGGCAGA GCAAGATCCT TACACGGATA AAAATTTCAC TAGAGCTAAG GATGCTGATG GCTGTGCAAT CTTAAGAGAG GAAAACGCAA GAGAGAGCAT TGAAAAAGCT AAATTAAACG ATGCTGAAAA ATGCAAGGAC CTTAAAAATG CTTTAGAATA TTACTCTAAA ATGCTGTCAG CAACTTTTTA TAACGATATG CTAGAATATT ATTCTAAAGC TTGCGAGTTA GGGGATTATT TTTTTGGTGA AGGCGTAACA GCCAAAGCTT GTGAGTTGAA CGATGCTAAA GAGGGTAAAG GCGTGGCAAA GGATGAAAAG AAGCTAGGAT TAAAAGAAGC ATGCGATATT

AGGGTTTTGT GTTTGGGGGC GTTGTGTTTA 50 AAAGAGCTTA TATTTTCAGG TATAACTATT 120 AAATATTTTG AAAAAGCTTG CAAATCAAAC 180 GTTTATTCTA GTGGTAAAGC CATAGCGAGA 240 CTTGAACACA CCGCTACTGC TAAAGTTTGT 3 00 TTAGCAGAGT TTTATTTTAA TGTAAACGAT 360 TCTTGTAAGT TAAATAATGT TGAAGGGTGT 420 ATAAAGGGTT TGAAAAAAGA TAAAAAAGAT 480 AATAACGGTG GAGGGTGTTC TAAATTAGGA 540 AAAGATTTCA AAAAAGCTTT TGAATATTCT S00 GGGTGTTACG CTCTAGCAGC GTTTTATAAT S60 CAAACGACAG AAAACCTTGA AAAGAGTTGC 720 CTCAAAGAAC AAAAACAATA A 771 (2) Information for SEQ ID NO: 14 (i) Sequence Characteristics:

(A) Length: 729 base pairs (B) Type: nucleic acid i

i i

145 (C) String: double · '' (D) Topology: circular '(ii) Molecule type: DNA (genomic),. , '' * '-''(iii)' Hypothetical: NO _; (iv) Antisense: NO. :

(vi) Original source:

(A) Organism: Helicobacter pylori.

~ fix) ^- FeaturesT:

(A) Name / Key: misc_character (B) Location: 1 ... 729 (xi) Sequence Description: SEQ ID NO: 14:

ATGAAAAAAT TTTTTTCTCA ATCTTTGTTA GCTCTTATTA TCTCTATGAA TGCGGTATCT 60 GGCATGGATG GTAATGGCGT TTTTTTAGGG GCGGGTTATT TGCAAGGACA GGCGCAAATG 120 CATGCGGATA TTAATTOTCA AAAACAAGCC ACCAACGCTA CGATCAAAGG CTTTGACGCG 180 CTCTTGGGGT ATCAATTTTT CTTTGAAAAA CACTTTGGCT / TÁCGCCTTTA TGGGTTTTTT 240 GACTACGCTC ATGCCAATTC TATTAAGCTT AÁAAACCČTA ACTATAATAG CGAAGCGGCG 300 CAAGTGGCTA GTCAAATTCT TGGGAAACAA GAAATCAATC GTTTAACAAA CATTGCCGAT 360 CCCAGAACTT TTGAGCCGAA CATGCTCACT 'TATGGGGGGG CTATGGACGT GATGGTTAAT 420 GTCATCAATA ACGGCATCAT GAGTTTGGGG GCTTTTGGCG GGATACAATT GGCCGGCAAT '480 TCATGGCTTA TGGCGACACC GAGCTTTGAG GGCATTTTAG TGGAACAAGC CCTTGTGÁGC 540 AAGAAAGCCA CTTCTTTCCA ATTTTTAŤTC AATGTGGGGG CTCGCTTAAG GATCTTAAAA 600 CATTCTAGCA TTGAAGCGGG CGTGAAATTC CCCATGCTAA AGAAAAACCC CTACATCACT 660 GCAAAAAATT TGGATATAGG GTTTAGGCGC GTGTATTCGT GGTATGTGAA TTACGTGTTC 720 ACTTTCTAG 729 (2) Information for SEQ ID NO: 15:

(i) Sequence characteristics:

(A) Length: 804 pairs. (B) Type: nucleic acid (C) String: double (D) Topology: circular (ii) Molecule type: DNA (genomic) (iii) Hypothetical: NO (iv) Antisense: NO (vi) Original source:

(A) Organism: Helicobacter pylori (ix)

ť ..

in

146

(A) Name / Key: misc_character (B). Location: 1 / .. 804 (xi) Sequence Description: SEQ ID NO: 15:

ATGAACTACC CTAATCTACC TAACAGCGCT TTAGAGATAA GCGAACAGCC AGAAGTGAAA 60. GAAATCACTA ACGÁGCTTTT AAAGCAATTA CAAAACGCTT, TAAGGAGCAA .CGCGCATTTT 120. AGCGAGCAAG TGGAATTAAG CCTTAAATGC ATCGTTAGG TTTTAGAAGT GCTTTTGAGT .18 0 .TTGGATTTTT. TTAAGAATGC GAATGAGATT. GATAGCAGTT.'TAAGAAATTC CATTGAGTGG · 240

CTGACTAACG CCGGCGAGAG CTTGAAATTA AAAATGAAAG. AATACGAGCG CTTTTTTAGC 300

GAGTTTAATA. CGAGCATGCA, TGCCAACGAG _: CAGGAAGTAA CCAATACCTT AAACGCTAAC 360

GCCGAGAACA TTAAAAGCGA AATTAAAAAG CTAGAAAATC AATTGATAGA AACCACGACA 420

AGACTTTTAA CGAGCTATCA AATCTTTTTA. AACCAAGCCA -GAGATAACGC TAACAACCAA-480ATCACAAAAA ACAAAACCCA AAGCCTTGAA GCGATTACAC AAGCTAAAAA CAACGCTAAT 540

AATGAAATAA GCAACAATCA AACGCAAGCG ATAACTAATA TCACCGAAGC GAAAACGAAC 600

GCTAATAATG AAATAAGCAA CAATCAAACG CAAGCGATAA CTAACATTAA CGAAGCCAAA 660

GAAAGCGCTA CAACGCAAAT AAACGCCAAT AAGCAAGAAG CAATAAATAA CATCACGCAA 720

GAAAAAACCC AAGCCACAAG CGAGATCACC GAAGCGAAAA AGACCGATCA TTATCAAAAC 780

ATTGATTTTT TTGAGTTTGA ATAA 804 (2) Information for SEQ ID NO: 16:

(i) Sequence characteristics:

(A) Length: 1632 pairs of cravings. (B) Type: nucleic acid, γ (C) String: double _; (D) Topology: circular (ii) Molecule type: DNA (genomic) (iii) Hypothetical: NO (iv) Antisense: NO (vi) Original source:

(A) Organism: Helicobacter pylori (ix)

(A) Name / Key: misc_charakter (B) Location: 1 ... 1632 (xi) Description of Sequence: SEQ ID NO: 16:

GTGATAGAGA CCATCCCCAA ACACTCTAAG ATTGTTTTAC CCGGGGAGGC GTTTGATAGT «a.

..., í · ··· ··

TTAAAAGAGG CGTTTGATAA AATTGACCCC TATACTTTCT TTTTŤČÍAJA. AťTŤGÁAGCC * · 12V ACTAGCACTT CTATTTCTGA TACTAACACG CAGAGGGTGT TTGAAACGCT CAATAAGATT 180 AAAACAAATC TTATAATGAA ATATAGTAAT GAAAATCCAA ACAATTTCAA CACTTGTCCT 240 TACAATAATA ATGGTAATAC AAAAAATGAT TGTTGGCAAA ATTTCACCCC ACAAACCGCA 300 GAAGAATTCA CCAATTTAAT GTTGAACATG ATCGCTGTCT. TAGACTCCCA ATCTTGGGGC 360 GATGCGATCT TAAACGCTCC TTTTGAATTC ACTAACAGCT CAACAGATTG CGATAGCGAT 420 CCTTCAAAAT GCGTAAATCC CGGAGTAAAT GGGCGTGTTG ATACTAAAGT CGATCAACAA 480 TATATACTCA ACAAACAAGG TATTATTAAT AATTTTAGAA AAAAAATAGA AATTGATGCG 54 0 GTTGTTTTAA AAAATTCAGG GGTTGTAGGG TTAGCCAATG GATATGGCAA TGATGGTGAA 600 TATGGCACAT TAGGGGTAGA AGCCTATGCT TTAGATCCTA AAAAACTCTT TGGCAACGAC 660 CTTAAGACTA TCAATTTAGA AGATTTAAGA ACCATCTTGC ATGAATTCAG CCACACTAAA 720 GGCTATGGGC ATAACGGGAA TATGACCTAT CAAAGAGTGC CGGTAACGAA AGATGGTCAA 780 GTGGAAAAGG ATAGTAATGG CAAGCCAAAA GATTCTGATG GCCTCCCCTA TAATGTGTGT 840 TCGCTTTATG GGGGATCCAA TCAGCCCGCT TTCCCTAGCA ACTACCCTAA TTCCATCTAT 900 CACAATTGTG CGGATGTCCCGGCTGGCTTT TTAGGGGTAA CAGCAGCGGT TTGGCAGCAG 960 CTCATCAATC AAAACGCCTT GCCGATCAAC TACGCTAACT TGGGGAGTCA AACAAACTAC 1020 AACCTAAAGG CTAGTTTAAA CACGCAAGAT TTAGCCAATT CCATGCTCAG CACCATCCAA 1080 AAAACCTTTG TAACTTCTAG CGTTACCAAC CACCATTTTT CAAACGCATC GCAAAGTTTT 1140 AGAAGCCCTA TTTTAGGGGT TAACGCTAAA ATAGGCTATC AAAACTACTT TAATGA TTTC 1200 ATAGGGTTGG CTTATTATGG CATCATCAAA TACAATTACG CTAAAGCTGT TAATCAAAAA 1260 GTCCAGCAAT TGAGCTATGG TGGGGGGATA GATTTGTTAT TGGATTTCAT CACCACTTAC 1320 TCCAATAAAA ATAGCCCTAC AGGCATTCAA ACCAAAAGGA ATTTTTCTTC ATCTTTTGGT 1380 ATCTTTGGGG GGTTAAGGGG CTTGTATAAC AGCTATTATG TGTTGAACAA AGTCAAAGGA 1440 AGCGGCAATT TAGATGTGGC TACCGGGTTG AACTACCGCT ATAAGCATTC TAAATATTCT 1500 GTAGGGATTA GCATCCCTTT AATCCAAAGA AAAGCTAGCG TCGTTTCTAG CGGTGGCGAT 1560 TATACGAACT CTTTTGTTTT CAATGAAGGG GCTAGCCACT TTAAGGTGTT TTTCAATTAC 1620 GGTGGGTGTT TT 1632 (2) Information for SEQ ID NO: 17:

(i) Sequence characteristics:

(A) Length: 1071 base pairs (B) Type: nucleic acid (C) String: double (D) Topology: circular (ii) Molecule type: DNA (genomic) (iii) Hypothetical: NO (iv) Antisense: NO ( (vi) Original source:

(A) Organism: Helicobacter pylori (ix)

(A) Name / Key: misc_charakter (B) Location: 1 ... 1071 (xi) Description of Sequence: SEQ ID NO: 17:

TTGATGAAAA GCATTTTGCT CTTTATGATT TTTGTAGTTT GTCAGTTAGA AGGCAAAAAA 60 TTTTCACAAG ATAATTTTAA GGTGGATTAT AACTACTATT TGCGCAAACA GGATTTGCAC 120 ATCATTAAAA CGCAAAACGA TTTGTCCAAT GCCTGGTATC TCCCTCCACA AAAAGCCCCC 180 AAAGAACATT CTTGGGTGGA TTTTGCTAAA AAATATTTAA ACATGATGGA TTATCTAGGC 240 • ·

148 · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · ·

ΑΟΤΤΑΤΓΤΓΤ TGCCTTTTTA TCATAGTTTC ACCCCCATTT. TTCAATGGTA CCACCCTAAT 300 ATČAACCCCT ACCAACGCAA TGAGTTTAAG TTCCAAATCA GTTTTAGAGT GCCTGTAŤTT 360 AGGCATATTC 'TTTGGACTAA AGGCACGCTT TATCTGGCTT ATACCCAAAC TAACTGGTTT 420 CAAATTTATA ÁTGACCCTCA ^of ATCCGCCCCC ATGCGAATGA TCAATTTCAT. GCCTGAACTC 480 ATCTATGTTT ATCCTATTAA 'TTTTAAACCT "TTTGGGGGTA AAATAGGGAA' TTTTTCTGAA 540 ATTTGGAtÁg.GTTGGCAGCA CATTTCTAAT GGTGTGGGGG GTGCGCAATG TTACCAGCCT 600 '^ TTTAATAAÁG AAGGTAATCC TGAAAACCAG TTTCCAGGAC AACCTGTAAT CGTTAAAGAT 660 TATAAČGGGC-AAÁAAGATGT GCGCTGGGGG GGGTGTCKTT CGGTGARCSC GGGCAACSCC 720 CTGTGTTTCG TTTTGGTGTG GGAAAAGGGA. GGCCTAAAAA TCATGGTCGC TTATTGGCCC 780 TATGTCCCTT ATGATCAATC CAACCCTCAA'TTGATTGATT ACATGGGGTA TGGTAACGCT 840 AAAATTGATT ACAGGAGAGG GCGCCÁCCAT TTTGAATTGC AACTTTATGA TATTTTCACG 900 CAAŤACTGGC GTTATGATCG CTGGCATGGA GCTTTCCGCT TAGGCTATAC CTACCGCATT 960 AACCCTTTTG TGGGGATTTA TGCGCAGTGG TTTAACGGCT ATGGCGATGG CTTGTATGAA 1020 TACGATGTTT TTTCCAATCG TATAGGGGTA GGAATACGOT TGAACCCTTA A 1071 (2) Information for SEQ ID NO: 18 (i) Sequence characteristics: · (A) Length: 2028 base pairs * (B) Type: nucleic acid '(C) String: double <' (D) Topology: circular ^{* 1} (ii) Molecule type: DNA (genomic) (iii) Hypothetical: NO (iv) Antisense: NO (vi) Original Source:

(A) Organism: Helicobacter pylori (ix)

(A) Name / Key: misc_charakter (B) Location: 1 ... 2028 (xi) Description of Sequence: SEQ ID NO: 18:

TTGTCTAAAG GTTTGAGTAT CGGTAATAAA GTGTGCGTGA GCATTTTAGG GGTGTCCTTA AGCGCTCTGC ATTCAATGCA AGATAGTTTG TTGGAAAACA CTTATACGAG CATGGGCATT AGAGAAATCA AAATCCAGTT GTTAAAAAAC GTGAGCATGT TTTTTAAAGA CAGAGAGGAT ACGATCAAGT TGATGGAAAA CCCGTCATTA AAAAATAAAG AAATTTCTAA AAGCTTGCCT GTTTATGGCG TGGATATTCTTTTACCACTA GTTCTGATGA TTTTCTTTTC 'CATTGACAGC

ATCATATTGT GCGTGGCGTT GATTGTGATC AACAGCAGGG TGAAAGAGAT TTTAAAAGAA CATTTCAAGG TTAAGGAAGT GCAAAGTGTT GTCAAAGAAA TGCTCCCTGA AGACACCAAA TTCATTTTAG CCAATTCGCA TGTCGCTGGG TTGAGATTGA CGCTTTTACG AGATAACGAT GGGAGTAACC CTTTAGCGCA AAAAGCGÁTG TATTACAGGA AAATGCCTAA CGGGGCGGAA TTCAAGGAAA ACACGCÁAGA AGTGGTGGGG TTCAGTAATG AAATCACTAA AAACAGGAGC

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480

540

500 '· 7Y

In · · · · · · · · ·

GATTTATTTT TAATTGGCGT GACAAATCCA TCACCGAAAT ATTTTAGAAA ATGGCTCTAA AATTTTTTAG CCGTTGAAAC AATTGGATGA TCGCTTTGAT 'CGTTTTGTGG TGGTTGCAGC CTTTTA

149

TAAAGGTAAA GTGCTTTTGA TTATAAAAGC GTGCCTAAAG AGCGACTTTA GAATACTTGG CTTTAAAATG CTAGGCAAAA CATTGAAAAA GACAAGGTCT GAGTGCTATC 'ATGGTGTTAG GAGCAATCG · · · · · · ·

GCGCGAATAA AAGCTTGCAA CCACTAATGA AGTGATGGCT ATCCCTTTAG CCATAAGGAG CAGAAAGTAA AGACAATCTT ATGAGCAAGT GGGATCGGTG CCTTAATCAT AGCGATCACT TTTCTAGCAC CTTGTCTCAT

TTCTTTAAAT TATTGAACAA TCAAGCCCAT TCTAATGACG AATTAGGGCG CATGCAAACA aaaaccatgc AAGAAGACAG gcaagccgtc AAAGCGGGGA ATTTTGCGGT GCGCATCACG TTGAGAGACG CGCTAAATGG GATCATGGAT CCAAGCATTT TCAAAATCTT TGAAAGCTAT AACGCTTCGG GTAGGGTGGA ATTGGTTACT CTAGAAACTT CGTCTAATTT; TGCCAAAGAT TGCGTGCAAA ATTTAGAAAA GGCTTCAAAC AAAACGATAG AAAATATCAC CACTTCCATT ATTGAACAAG GGAAAGACAT TAAAAGCATT. ACGAATCTAT TAGCCCTAAA CGCŤGGTAŤT GGCTTTGCGG TGGTGGCTGA TGAGGTGAGG 'AGTGAGATTG AAGCCAATAT TAATATTCTC ATTAAAAACC AGGTTAAAGA AGTAGAAGAG GTTACTGAGG GCAATCTAAA AATCGCTAGC

TCTAGCGACA TTAAATTGGT TGAAGCGCGA GCGATCAATA AAAATATCTT GCAAACCCAA CAAGACACCA TTAAAGTGGT- TTCAGACGTG gctgaacccg. caagccctga tttgaaagaa TATTTGCAAG AAAGCGTAGG · GACTCACATG TCTGGCTTGG ATTTTAGAGG GCGGATCCAA aacgctttag GGCAAGAAAT CCAAAAAATG ČTAGCGAACG ATAGCGCGAA TTTAAAAGAA TCCCAACACA AAAGCCTGAT GGAAACTTCC CAAGGCGTGA GCTOTCAÁAG TGAAGCCATG GTAGAAATCA TTAGAGATAT TGCČGATCAA GAAGCCGCACGAGCCGGCGAGCATGGCAGA AAGCTCGCTG AAAGGACGCA AAAATCCCTC GTTCAAAGCA TTTCAGACAC GAGCGAAAGC ATCAACGCTT CTATTGAAGC CTTAAGATCG GATTCTTTAG AAATCAGTCA AGAAATTGAC AATAAAAAGC AGTTTTAA • ·

560 720 730 340 900 960

1020 .1080

1140

1200

1260

1320

1380

1440

1500

1560

1620

1580

1740 ------- 1800

1860

1920's

1980

2028 (2) Information for SEQ ID NO: 19:

(i) Sequence characteristics:

(A) Length: 816 base pairs (B) Type: nucleic acid (C) String: double (D) Topology: circular (ii) Molecule type: DNA (genomic) (iii) Hypothetical: NO (iv) Antisense: NO ( (vi) Original source:

(A) Organism: Helicobacter pylori (ix)

(A) Name / Key: misc_charakter (B) Location: 1 ... 816 • ·

150 (xi) Sequence description: SEQ ID NO: 19:. ATGAACATAT TCAAGCGTAT TATTTGCGTA ACCGCTATTG TTTTAGGTTT TTTTAACCTT

TTAGACGCCA AACACCACAA AGAAAAAAAA GAAGACCACA AAATCACTCG TGAGCTTAAA GTGGGCGCTA ACCCTGTGCC GCATGCGCAA ATCTTGCAAT CAGTTGTGGA TGATTTGAAA GAGAAAGGGA TCAAATTAGT GATCGTGTCT TTTÁCGGATT ATGTGTTGCC TAATTTAGCG CTCAATGACG GCTCTTTAGA CGCGAATTAC 'TTCCAGCACC GCCCTTATTT GGATCGGTTT. AATTTGGACA GAAAAATGCA CCTTGTTGGT TTGGCCAATA TCCATGTGGA GCCTTTAAGA TTTTATTCTC AAAAAATCAC AGACATTAAA AACCTTAAAA- AAGGCTCAGT. 'GATTGCTGTG CCAAATGATC. CGGCCAATCA. AGGCAGGGCG. TTGATTTTAC, TCCATAAACAAGGCCTTATC GCTCTCAAAG ACCCAAGCAA TCTATACGCT ACGGAGTTTG ATATTGTCAA AAATCCTTAC AACATCAAAA TCAAACCCCT AGAAGCTGCG TTATTGCCTA AGGTTTTAGG GGATGTGGAT GGGGCTATCA TAACAGGGAA TTATGCCTTG CAAGCftAAAC TCACCGGAGC CTTATTTTCA -GAAGATAAGG "ACTCGCCTTA-TGCTAATGTT-GTAGGGTCTG-GTGAGGATAA-TGCGCAAGAT. GAAGCGATAA AAGCGTTGAT TGAAGCCTTA CAGAGCGAAA AGACCAGGAA ATTCATTTTG GATACCTATA AGGGGGGCGAT TATCCCGGCT TTTTAA (2) Information for SEQ ID NO: 20:

(i) Sequence characteristics:

(A) Length: 486 base pairs (B) Type: nucleic acid (C) String: double (D) Topology: circular (ii) Molecule type: DNA (genomic) (iii) Hypothetical: NO '(iv) Antisense: NO (vi) Original source:

(A) Organism: Helicobacter pylori (ix)

(A) Name / key: misc_charakter (B) Location: 1 ... 486 (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 20: atgtttttta aaacttatca aaaattactg ggcgcgagct gtttggcgct gtatttagtg GGCTGTGGGA ATGGTGGTGG CGGTGAATCG CCGGTTGAGA TGATTGCAAA TAGCGAGGGT ACGTTTCAAA TCGAOTCCAA agcagatagc attactattc aaggcgtgaa gcttaataga GGTAATTGTG CTGTCAATTT TGTTCCAGTA AGTGAGACGT TTCAAATGGG TGTTTTAAGT CAAGTTACTC CAATCTCTAT ACAGGATTTT AAAGATATGG CAAGCACTTA TAAGATATTT GATCAAAAGA AAGGGTTGGC AAACATAGCA AATAAAATTT CTCAATTAGA GCAAAAGGGT GTGATGATGG AACCTCAAAC CCTTAATTTT GGAGAAAGTT TAAAAGGCAT TTCTCAAGGG TGCAATATTA TAGAGGCAGA AATACAAACC GACAAAGGCG CTTGGACTTT TAACTTTGAT AAATAA (2) Information for SEQ ID NO: 21:

(i) Sequence characteristics: 60

120

180

240

300

360

420

480 '

540

600

660

7.2JD ..

780

816

120

180

240

300

360

420

480

486

151 ··· ··· (A) Length: 1014 base pairs (B) Type: nucleic acid (C) String: double (D) Topology: circular (ii) Molecule type: DNA (genomic) (iii) Hypothetical: NO (iv) Antisense: NO (vi) Original Source:

______ (A) —Organism: —Hel-icobaoter ^ pylori ---------------------- (ix) Features:

(A) Name / Key: misc_charakter (B) Location: 1 ... 1014 (xi) Sequence Description: SEQ ID NO: 21:

ATGATTAGAT TAAAAGGTTT GAATAAAACT TTAAAAACAA GCTTATTAGC TGGGGTTTTA SO 'CTAGGTGCTA CTGCTCCCTT AATGGCAAAG CCTTTATTAA GCGATGAAGA CTTATTGAAA 120

CGAGTAAAAC TACACAATAT CAAAGAAGAT ACGCTGACTA GCTGTAATGC TAAGGTGGAC 180

GGCTCTCAAT ACTTGAATAG TGGTTGGAAT TTATCTAAAG AATTTCCGCA AGAATATAGA 240

GAAAAGATTT TTGAATGCGT AGAAGAAGAA AAACATAAAC AAGCCCTTAA TTTAATCAAT 300

AAAGAAGACA CTGAAGATAA AGAAGAACTT GCAAAAAAAA TCAAAGAAAT TAAAGAAAAA 350

GCTAAAGTTT TAAGGCAAAA ATTTATGGCT TTTGAAATGA AAGAACACTC TAAAGAATTC 420

CCAAATAAAA AGCAACTTCA AACCATGCTT GAGAACGCTT TTGATAATGG AGCTGAAAGT 480

TTTATTGATG ATTGGCACGA ACGCTTTGGG GGTATAAGTA GAGAGAATAC TTATAAAGCA 540

CTTGGCATTA AAGAATATAG TGATGAAGGA AAGATATTAG CCTTTGGCGA AAGAAGTTAT 600

ATTAGACAAT ATAAAAAAGA TTTTGAAGAA AGCACTTATG ATACTAGACA AACCTTATCT 660

GCTATGGCTA ATATGAGTGG CGAAAACGAT TATAAAATTA CTTGGTTAAA ACCCAAATAT 720

CAGCTCCATA GTTCAAATAA TATTAAACCC TTAATGTCAA ACACAGAGTT GTTAAATATG 780

ATAGAGCTAA CCAATATCAA AAAAGAATAT GTTATGGGCT GTAATATGGA AATAGATGGT 840

TCTAAATATC CCATTCATAA AGATTGGGGA TTTTTTGGTA AGGCAAAAGT CCCAGAAACT 900

TGGAGAAATA AGATTTGGGA ATGTATTAAG AATAAAGTAA AGTCCTATGA CAACACTACC 960

GCTGAAATAG GAATAGTTTG GAAAAAAAAT ACTTATTCTA TCTCTCATCA CTAA 1014 (2) Information for SEQ ID NO: 22:

(i) Sequence characteristics:

(A) Length: 1251 base pairs (B) Type: nucleic acid (C) String: double (D) Topology: circular (ii) Molecule type: DNA (genomic) (iii) Hypothetical: NO ···· 99 99 • φ 9 9 9 9

152

999 999 (iv) Antisense: NO (vi) Original Source:

(A) Organism:

(ix) Features:

(A) Name / Key:

(B) Location: 1

Helicobacter pylori misc_character

..1251 (xi) Description of sequence: SEQ ID NO: 22:

ATGAAAAAAT TAGTTTTTAG CATGCTTTTA TGTTGTAAAA GCGTGTTTGC AGAGGGGGAA 60

ACTCCTTTGA-TTGTCAATGA-CCCAGAAACC-CATGTAAGTCAAGCCACTATCATAGGCAAA ----- 120 - ATGGTAGATA GTATCAAAAG ATACGAAGAG ATTATTTCTA AGGCTCAAGC TCAAGTCAAT 180 CAGTTACAAA AAGTCAATAA CATGATAAAT ACGACTAATT CTTTGATTAG TAGTAGTGCT 240 ATCACTTTAG CCAATCCTAT GCAAGTTTTA CAAAACGCTC AGTATCAAAT AGAGAGCATT 300 AGATACAACT ATGAGAATTT AAAGCAAAGC ATAGAAAATT GGAACGCACA AAATTTGTTA 360 AGAAACAAAT ACTTACAGCA ACAATGCCCT TGGCTTAATG TCAATGCTCT TACTAACAAT 420 AAGATTGTCA ATCTTAAAGA TCTCAATAAC CTAATCACCA AAAATGGCGA ACAAACCCAA 480 ACCGCAAGAG ATGTGCAAAA TCTCATTCAG TCCATTAGTG GCAGTGGCTA TGGAAACATG 540 CAATCACTTG CTGGGGAATT GAGTGGTAGA GCGTGGGGGG AAATGTTGTG TAAAATGGTA 600 AACGATAGTA ATTATGAAAG CGAGCAAGCT CTTTTAGCAA CAGGCAATAA CCCAGAAGAG 660 CAAAAACGAA GATTTTTGCT TAGAGTAAAG AAAAAGGTTA ATGATAATAA 'GCAGTTAAAA 720 GATAAACTTG ACCCATTTCT AAAAAGACTT GATGTCCTAC AAACTGAGTT TGGTGTAACT 780 GACCCTACAG CTAACCATAA TAAGCAAGGG .ATACATTATT GCACAGAAAA TAAAGAGACA 840 GGTAAATGCG ACCCTATTAA AAATGTATTT AGGACAACTC GCTTAGATAA CGAATTAGAA 900 CAAGAAATCC AAAC GCTCAC ACTTGATTTA ATCAAAGCCT CCAATAAAGA CGCTCAAAGC 960 CAAGCCTACG CAAATTTCAA TCAAAGGATT AAATTACTTA CTCTAAAATA TTTAAAAGAA 1020 ATTACCAATC AAATGCTCTT TTTAAATCAA ACAATGGCAA TGCAAAGCGA GATTATGACA 1080 GATGATTATT TTAGGCAAAA TAATGATGGC TTTGGGGAAA AAGAAAACCA TATAGACAAA 1140 CAATTAACGC AAAAAAGAAT AAACGAAAGA GAAAGAGCTA GAATATACTT TCAAAACCCT 1200 AATGTTAAAT TTGACCAATT TGGCTTTCCC ATTTTTAGTA TATGGGATTA A 1251 (2) Information for SEQ ID NO: 23:

(i) Sequence characteristics:

(A) Length: 1131 pairs (B) Type: nucleic acid (C) String: double (D) Topology: circular (ii) Molecule type: DNA (genomic) (iii) Hypothetical: NO (iv) Antisense: NO ( (vi) Original source:

(A) Organism: Helicobacter pylori

153

(ix) Features:

(A) Name / Key: misc_charakter (B) Location: 1 ... 1131 (xx) Description of Sequence: SEQ ID NO: 23:

GTGAATAAGT GGATTAAAGG. TTTTCTTTAA TCTACCACCA AATGACGATG AGGTGAAATA ACTAACACGG AAAGCTCCAA GCTTTAAAAG. CCCTAAACTC CCTCCCATGG ATCCAAAAAC TTACTGGCCT CTCGCATCAC 7ATTTTCCCTG TGGATAACCC ATCGCCACTA ATGAAAACAA TTTTTGATTA CGCCCATTTC GATATTTTTG CAAGCATGGG TATTACAGCA ACAATAACAA ATCACTCCCC ATGGCATTAA TATAACGGOT TAGTGGGGGA CTGCTTTCTA CGCTCACTAA GGCAATAAAG AAGAGGTGAC CAAAGCGGCA TGGGGATCAA GCCCCCATTG TGGTGATTAG TTCTTCCCTA TACCCAGAGA (2) Information prc

GGCGGTTGTT TTTGTAGGGG AAAGCCAAAA GCCCCCCTAA CCCCTTACAA GACTACACTT AGACGCTACC ATCAAAGCCT CAAAGAAATG AATTATTCCA AACCCCCCCT AAAAAAGACT CCCTTTCAAG CAAAGCCCTA TAATGGCATT GATAGTTTCA GCTTTTACGC ACCATTACAG TAGCCAGATC GCTGGTAAAG CAAAGCCGTC TTAATCCCCA AATGGGCGAA TACCGCTTGG TATCATGCTC ACTAACGCTA ATTGATTGAA AGGAATTTCC. CGGCCTATTG ATTGGGATCA Taatttcttt ggggattatc TCAAGTGGTC AATCAAATTT AGAGGGGAGT AGGGTCTTCA GAATGAAGTC ATCGCTGAGT

GTTTTGCAAC- GATTACAACC ATAACCAGCC TAGCCTTTTG TCACTCAAAA CCCACAGCCA TACAAGAACA .GCTCAAAGCC AAGAAGAGAC TTTTACTAGC TTTCTCCAAA ACAATTAGAT AAAATTACGA AGAAAACCTG CTAACCTTAA AGAAAAAGAC CTGACAAAAT GATACCCGCT TGATTGCGCA AGTGGAGAGC AAGGCTCTAA AGTCATAGGC ATATTGTATG GAGTCGAATC AAGGGGCGGA CATTAAAGGC AACGCTATGG CGTGCCGTTA CTTCGGCTTT AAACAACAGA TTTTATTGCA ATTGATGAGG TAAGAGACAA GAGCAAGATC TTTCGCCCAA TACTGACATC TTTTGAAGTG A

120

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540

600

660

720

780

340

900

960

1020

1080

1131 (i) Sequence characteristics:

(A) Length: 2751 bp (B) Type: nucleic acid (C) String: double (D) Topology: circular (ii) Molecule type: DNA (genomic) (iii) Hypothetical: NO (iv) Antisense: NO ( (vi) Original source:

(A) Organism: Helicobacter pylori (ix)

(A) Name / Key: misc_charakter (B) Location: 1 ... 2751 (xi) Description of Sequence: SEQ ID NO: 24:

GTGGATTTGA GGAŤCCAATC TAAAGAAGTC AGTCATAATT TAAAGGAATT ATCAAAAACG CTAATCAGCT ATCCTTTTGA AAAACATGTA GAAGCTTTAG GGGAACAATG CAGTAACTTC GTTTCTATTC CCATTAACAA TGACGACTAT TCAAATATTT GCACTTTTGT GAGTGATTTT ATAAATCTTA TAGCTTCTTA CAATTTATTA GAATCATTTT TAGATTTTTA TAAAGATAAA TTAAAATTGA GCGAGCTTGT AACTGAATAT GCCAACGTAA CCAATAATCT GCTTTTCAAA AAATTAATCA AACATTTAAG CGGCAACAAT caattggtta aaaattttta tcagtgtata AGAGAAATTA TAAAATACAA CGCCCCTÁAT AAAGAATACA AACCCAATCA ATTTTTTATA

120

180

240

300

360

420

t.

ATAGGGAAAG GCAAACAAAA GCAAGTGAAA TTAAACCACA AAAATTTTTA AAACTACCGA ATTAAAGAAA TAGACGAAAA TTTGAATCAA ATATTGAAAA TCGCTGATCC GAGAAATTGA GAGTATAAGA TTAATGATCT AGTCATGCCG TTAATGATGT AAACAGATAG ATTTATTAGT GAACCAATAC.AAAGATCTTT TATTTGTTCC CTAAAAATAT .TTCAAACAAA GCAAAAATGT ACAGCGTTTA ACTTTCATCT GTGCCAATCA TGAAAGAATA TCAACCAAAG AGACTGGTČT TTATTTAATA AAACAAACTT AGATCAAAAA TAAAGTTTGA AATATCTCTA AAAAATACTT TCAAAAGATT TTTTTTCAAT -CAACTTGAAT "TiTiTGAUAA ATTTTAGAAT ACAACATGCA CTTTTAGCGA TCGTTCAAGA CATAACAATA AGCTTCCTAG GATTGCAGAA AATCCCACGA TTCCAATGGG CGTTTAATTT TTTAACCATA ATATTATCTA agaaaggagt

154

ACAATTAGCA AAAATTTATT AGATATGGAA GACATCTTAA CTTTACAAAA TTCACACCAA ATACCCTATC AATGAAAATT ACATGATGAA ATAAAAAAGG AAATCACTGC AAAAATGAAT GCTCAAAAAT ATCCAACAAA GTCTAAAGAT ATTAAATCCA CAATTCAGAA ATTGTGCGAT ATGGGAGAGT ATAAAAATTT TGGTGAAATC AAGGATAAAT TTCTGAGTTC, GCAGAATATT AAATATAAAT AATGGTTTAT CAAAGAGCCA AAAATCACAG TGCTAGCCAA TTATCTGGGC TAATCCTAAT AAAATTTGGA TAAAGATTTA GAAATCTATT GCAAGAAATA GATCAAGAAT TCAAAAAATA GAGAGTAAGC TGATACAAGT TTTCTTTTTG ATTAAAAATA GATTCTTTAA TAGTCCCCAA GATAGTTACC AGAGAAATAT ACGGAACATG TCACAATGAG CCAATCATCT CATGTTTGGC TTTCTTTATA TGTCATGGAC GAGCCAGCCA TTTAAAAGAA TACGCTCATA ·· ····

• · · · · · · · · · · · ··· ···

CTCATTTAAA AGAACTTAGA AAAAGCTAGA GGAATTAGAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA GCCGAGAGTG TAACCCCTAT GTCATCAATT TGAAAAATTC ATAATGACCT.TGAAGCCATA ACTGGTTTTT TCAGCTTTCG ‘TTCCTTTAGA 'GTTCAATAAA TTGATAGTCA' TGAATCGTTC CACTAAAAAA GATCAAACAA. ATGATAATAA CGATATACTG CTAAAGGAAG TTTTGCAGAA ATACTAAAAAA ATTTAATAAG AATTAAAAAT TCGTGTCCGA AAATAAAACT TGAAGTTTAT TAAGCCAGCA AAGCACCGGC ATGTGGGATC

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's

1980

2040

TTAGCCACCC ATGACCCCTT TTTAGTGGAT ACGGATCATT TAGATGAAAT. AAGGATTGTG 2100 GAAAAGGAAA CAGAAGGCTC TGTAATTAAAG AATCACTTTA ACTATACCCCT. AAATAATGCA 2160 AGCAAAGAGT CCGACGCTTT GGACAAAATC AAACGCTCTT TAGGAGTGGG CCAGCATGTT 2220 TTTCATAACC CCCAAAAACA CCGAATCATT TTTGTAGAAG GCATCACGGA TTATTGTTAT. 2280 TTGAGCGCTT TTAAATTGTA TTTGCGTTACAAAGAATACA AGGACAACCC CATTCCTTTC 2340 ACTCTCTTAC CCATTTCAGG GCTTAAAAAC GATTCAAACG ATATGAAAGA AACCATTGAA. 2400 AAACTTTGCG AGTTAGACAA TCACCCTATT GTŤTTGACAG ACGATGACAC AAAATGCGTT 2460 TTTAACCAAC AAGCAACGAG CGAACGATTT AAAAGAGCTA ATGAAGAAAT GCATGÁTCCC 2520 ATCACCATCC TACAACTCTC AGACTGCGAT AGGCATTTCA AACAAATTGA AGATTGTTTC 2580 AGCGCAAACG ATAGAAACAA ATACGCTAAA AATAAGCAAA TGGAATTGAG CATGGCTTTT 2640 AAAACAAGGC TTTTGTATGG CGGAGAAGAT GCGATAGAAA AACAAACAAA AAGAAATTTT 2700 TTAAAATTAT TCAAATGGAT TGCATGGGCT ACAAACTTGA TCAAAAACTA A 2751 (2) Information for SEQ ID NO: 25:

(i) Sequence characteristics:

(A) Length: 531 bp (B) Type: nucleic acid (C) Chain: double (D) Topology: circular (ii) Molecule type: DNA (genomic) (iii) Hypothetical: NO

155 ·············································· 9 9 (9) 9 (9) (iv) Antisense: "NO" (vi) Original source. · (A) Organism: Helicobacter pylori (ix) Properties:

(A) Name / Key: misc_charakter (B) Location :. 1 ... 531 (xi) Description of sequence: SEQ ID NO: 25:

ATGACTGCAA TGATGCGTTA TTTTCACATC TATGČGACCA CTTTTITCTT CCiTTTGGCG CTTCTTTTTG CGGTTAGTGG GCTTTCATTG CTCTTTAAAG CGCGCCAAGA CACTGGCGCT AAGATCAAAG AATGGGTTTT AGAAAAATCC TTAAAAAAAG AAGAACGATT GGACTTTTTA AAAGGCTTTA TAAAAGAAAA CCATATCGCT ATGCCTAAAA AGATAGAGCC TAGAGAGTAT AGGGGAGCGT TAGTCATTGG CACGCCTTTG TATGAAATCA ACCTTGAAAC TAAAGGCACT CAAACGAAAA TCAAGACCAT TGAAAGGGGC TTTTTAGGCG CGCTCATCAT GCTGCATAAG GCTAAGGTGG GCATCGTGTT TCAGGCGCTT TTAGGGATTT TTTGCGTGTT TTTATTGTTG TTTTACTTGA GCGCGTTTTT AATGGTGGCT TTTAAAGACA CTAAACGCAT GTTTATAAGC GTTTTAATAG GGAGCGTGGT GTTCTTTGG GCGATCTATT GGTCTTTGTA G

120

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420

480

531 (2) Information for SEQ ID NO: 26:

(i) Sequence characteristics:

(A) Length: 669 base pairs (B) Type: nucleic acid (C) String: double (D) Topology: circular (ii) Molecule type: DNA (genomic) (iii) Hypothetical: NO (iv) Antisense: NO ( (vi) Original source:

(A) Organism: Helicobacter pylori (ix)

(A) Name / Key: misc_charakter (B) Location: 1 ... 669 (xi) Sequence Description: SEQ ID NO: 26:

ATGTTTAAAA ACGCTTTAAA TATACAAGAT TTTTCATTTA AAAATCATAC TAGTACAGCC 60

ATTATTGGCA CAAATGGTGC TGGAAAATCA ACGCTTATCA ACACTATTCT AGGCATTAGA 120

TCAGACTATA ATTTTAAAGC ACAAAACAAT AATATTCCAT ACCACGACAA TGTTATACCA 180

CAACGCAAGC AATTGGGAGT TGTCTCTAAC CTATTCAACT ACCCACCTGG ATTAAACGCA 240

AACGACCTTT TTAAATTCTA TCAATTTTTT CACAAAAACT GCACTCTAGA TTTGTTTGAA 300; .

AAAAATCTTT TAAATAAAAC CTACGAACAC CTAAGCGACG GACAAAAACA GCGCTTAAAA 360!

ATTGACTTAG CTCTTAGCCA TCAGCCACAA TTAGTTATTA TGGATGAACC AGAAACCAGT 420 j ₄

TTAGAGCAAA ACGCTCTTAT AAGACTATCA AATCTCATAA GCTTGCGCAA CACCCAACAA .480

CTTACAAGTA TCATCGCCAC TCATGATCCT ATTGTCTTAG ATAGTTGCGA ATGGGTATTG. 540

CTCCTTAAGA ATGGCAACAT TGCTCAATAC .AAACCTTTAA ’aTTCTATATT AAAATCTGTA 600’ ·· ... · 'GCTAAAACTT TTAACTTTAA AGAAAAACCA ACCACAAAAG · ACTTATTAGC GTTACTAAAG 660 GATATTTAA. . 669 i - i * · »| -'l’ ·

156 ftftftft ftft ftft ft ft <ftp ft ft ft ft ft ft ft ft

Ftftft ftftftftftftftftftftftftftft (2) Information for SEQ / ID NO: 27:

(and). Sequence characteristics:

(A) Length: 1221 base pairs (B) Type: nucleic acid (C) String: double (D) Topology: circular (ii) Molecule type: DNA (genomic) (iii) Hypothetical: NO (iv) Antisense: NO ( (vi) Original source:

(A) Organism: Helicobacter pylori (ix)

(A) Name / Key: misc_charakter (B) Location: 1 ... 1221 (xi) Description of Sequence: SEQ ID NO: 27:

ATGTATGCGG CTCATCCTAT TAAACCCATA AAAGCCCCTA AACTCAAATC TCAATTTTTA 60

AGGCGTGTGT TTGTGGGCGC GTCCATTAGG CGCTGGAATG ACCAAGCATG CCCTTTGGAA 120

TTTGTGGAAT TAGACAAGCA AGCCCATAAA GCGATGATTG CGTATCTGCT CGCTAAAGAT 18 0

TTAAAAGATA GGGGTAAAGA TTTAGATTTA GATCTTTTAA TCAAATATTT TTGCTTTGAG 24 0

TTTTTGGAGC GCTTGGTTTT AACCGATATT AAACCCCCTA TTTTTTACGC CCTCCAACAA 300

ACGCATAGTA AAGAGTTAGC TTCCTATGTT GCGCAAAGTT TGCAAGATGA AATCAGTGCG 360 TATTTTTCTT TAGAGGAACT CAAAGAGTAT TTAAGCCACA GGCCTCAAAT TTTAGAAACT 420 CAAATTTTAG AGAGCGCGCA TTTTTATGCG TCTAAGTGGG AGTTTGATAT TATCTATCAT 480 TTTAACCCCA ACATGTATGG CGTGAAAGAG ATTAAAGATA AAATTGACAA GCAACTCCAC 540 AATAACGATC ATTTGTTTGA AGGGCTTTTT GGGGAAAAAG AAGATTTGAA AAAATTGGTG 600 AGCATGTTTG GGCAGTTGCG TTTCCAAAAG CGCTGGAGCC AAACCCCAAG AGTGCCACAA 660 ACCAGTGTTC TAGGGCATAC TTTATGCGTG GCGATTATGG GGTATTTATT GAGTTTTGAC 720 TTGAAAGCTT GTAAAAGCAT GCGGATCAAT CATTTTTTGG GCGGGCTTTT CCATGATTTA 780 CCCGAAATTT TAACCCGAGA CATTATCACG CCCATCAAAC AAAGCGTTGC AGGGCTTGAT 84 0 CATTGCATTA AAGAGATTGA AAAAAAGGAA ATGCAAAACA AAGTCTATTC CTTTGTGTCT 900 TTGGGCGTTC AAGAAGATTT GAAATATTTC ACCGAAAACG AGTTTAAAAA CCGCTACAAA 960 GACAAGTCTC ATCAAATCGT TTTCACTAAA GACGCTGAAG AATTATTCAC GCTTTATAAT 1020 AGCGATGAAT ATCTTGGGGT TTGCGGGGAG CTTTTGAAGG TGTGCGATCA TTTGAGCGCG 1080 TTTTTAGAAG CCCAAATCTC ŤCTTTCTCAT GGCATTTCTA GCTACGATTT AATCCAAGGA 1140 GCTAAAAACC TTTT AGAATT / GCGATCCCAA ACGGAACTGC TTGATTTGGA TTTAGGGAAA 1200 TTGTTTAGAG ATTTTAAGTA A 1221 · t tt tt tt t tt · · · ·

-I ΖΣ 7 · · · ·

Λ O / · · · 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 (2) Information for SEQ ID NO: 28:

. (i) Sequence characteristics: —————---------. (A) Length: 1008 base pairs (B) Type: nucleic acid (C) String: double (D) Topology: circular (ii) Molecule type: DNA (genomic) (iii) Hypothetical: NO (iv) Antisense: NO ' __________________________ (vi) Original source:

(A) Organism: Helicobacter pylori (ix)

(A) Name / Key: misc_character (B) Location: 1 ... 1008 (xi) Sequence Description: SEQ ID NO: 28:

GTGTTGTGGG TGCTATATTT TTTAACCAGT TTATTTATTT GCTCTTTGAT TGTTTTGTGG 60 TCTAAAAAAT CCATGCTCTT TGTGGATAAC GCTAATAAAA, TCCAAGGCTT CCATCATGCA 120 AGAACCCCAC GAGCCGGGGG GCTTGGGATC TTTCTTTCTT TTGCGTTGGC TTGTTATCTT 180 GAACCTTTTG AGATGCCTTT TAAGGGGCCT TTTGTTTTCT TAGGGCTATC GCTAGTGTTT 240 TTGAGCGGTT TTTTAGAAGA CATTAACCTT TCATTAAGCC CCAAAATACG CCTTATTTTG 300 CAAGCTGTAG GGGTCGTTTG CATCATTTCA TCAACGCCTT TAGTGGTGAG CGATTTTTCG 360 CCCCTTTTTA GCTTGCCTTA TTTCATCGCT TTTTTATT.CG CTATTTTTAT GCTGGTGGGT 420 ATCAGTAACG CTATTAATAT CATTGACGGG TTTAACGGGC TTGCATCTGG GATTTGCGCG 480 ATCGCGCTTT TAGTCATTCA TTATATAGAC CCTAGCAGTT TGTCTTGTTT GCTCGCTTAC 540 ATGGTGCTTG GGTTTATGGT GTTAAATTTC CCTTCAGGAA AGATTTTTTT AGGCGATGGG 600 GGGGCGTATT TTTTGGGTTT GGTGTGCGGG ATTTCTCTCT TGCATTTGAG TTTGGAGCAA 660 AAAATCAGCG TGTTTTTTGG GCTCAATTTA ATGCTTTATC CGGTCATAGA GGTGCTTTTT 720 AGTATCCTTA GGCGCAAAAT AAAACGCCAG AAAGCCACCA TGCCGGATAA TTTGCATTTG 780 CACACCCTTT TATTTAAATT CTTGCAACAA CGCTCTTTCA ATTACCCTAA CCCTTTATGC 840 GCGTTTATCC TTATTCTA TG CAACCTGCCT TTTATTTTAA TAAGCGTTTT GTTTCGCTTG 900 GACGCTTATG CGCTCATTGT GATTAGCCTA GTCTTTATCG CATGCTATTT AATAGGCTAT 960 GCTTATTTGA ATAGGCAAGT TTGCGTTTA GAAAAGCGGTTTA GAAAAGCGG

(i) Sequence characteristics:

«· ·· · Β Β ·

Β ΒΒΒ

Β · Β Β · • Β Β

9ΒΒΒΒΒΒ ΒΒ

158 · · · · · · · · · · · · · · · · ·

A Β A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A

_______ (Β) Type: nucleic acid, ___ '____ (C) String: double (D) Topology: circular (ii) -Molecule type:' DNA (genomic) · * (iii) Hypothetical: NO (iv) Antisense ': NO (vi) Original source:

—- (A -) - Organism -: - Hel-Roterobyl-Ori ------------ (ix) Properties:

(A) Name / Key: misc_charakter (B) Location: 1 ... 291 (xi) Sequence Description: SEQ ID NO: 29:

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

(i) Sequence characteristics:

(A) Length: 471 bp (B) Type: nucleic acid (C) String: double (D) Topology: circular (ii) Molecule type: DNA (genomic) (iii) Hypothetical: NO (iv) Antisense: NO ( (vi) Original source:

(A) Organism: Helicobacter pylori (ix)

(A) Name / Key: misc_charakter (B) Location: 1 ... 471

··· »

159 «··« '# * • · •.

Sequence description: SEQ. NO ID: 30:

ATGCGAGATT TCAATAACAT TCAAATCACA CGCTTAAAAG. TGCGTCAAAA TGCCGTTTTT GAAAAACTGG ATCTGGAGTT TAAAGATGGC TTGAGCGCGA TTAGTGGGGC TAGTGGGGTG GGGAAAAGCG .TCCTTATTGC GAGCCTTTATA GGGGAGCGTTG

TCAAACATTG AAGTGGAATT GATCGCGCCT. TTTTTAGACA · CGGAAGAATA CGGCATTTTT AGAGAAGATG AGCATGAACC CTTAGTTATT AGCGTGATTA AAAÁAGAAAA, AACACGCTAT TTTTŤAAACC AAACAAGCCT ATCTAAAAAC ACGCTCAAAG CGTTATTAAA GGGGCTTATT AAACGCTTAT CTAACGACAG ATTCAGCCAG AATGAACTCA-ACGATAŤTTT / AATGCTCTCC TTATTAGATG GCTATATCCA AAATAAAAAT AGGCGTTTAG CCCCCTTTTA G _ (_ 2) _ Jnformace for SEQ ID NO: 31: _

SO

120

180

240

300

360

420

471 (i) Sequence characteristics:

(A) Length: 357 pairs (B) Type: nucleic acid (C) String: double (D) Topology: circular (ii) Molecule type: DNA (genomic) (iii) Hypothetical: NO (iv) Antisense: NO ( (vi) Original source:

(A) Organism: Helicobacter pylori (ix)

(A) Name / Key: misc_charakter (B) Location: 1 ... 357 (xi) Sequence Description: SEQ ID NO: 31:

GTGATGCTAA

ATGAGTTTAT

TTAAATGATT

AGCAGAAAGG

AAAGAACAAG

AAAAAATTTG

TGGCAATTTT

TCGCCAATAT

TTGTTTTTGG

CTATGGAAAA

TAGATATTAG

ATTTTGTTAT

TACCCCTTAT

GGGGTTGGAG

TATAGAAGTG

TCATCTTATC

AGAATTTGAG

TTTTAGCAAA

ATTCTTATTT

CAAATTTTTT

GGGCTTGATA

GGTCTTTTTG

GATTTACGCC

GAGAAAACTT

TGAAAATGAT

GCAACAGAGA

GCAATGCGAG

TCCAAGCTCA

AGGCTTTTGG

ATTTTCATAG

GAAAAAGTCT

CATTAAAGAT

AAAAAATCGT

ΑΤΓΑΑΑΤΤΤΤ

AAATGATACT

AAGCTAA

120

180

240

300

357 (2) Information for SEQ ID NO: 32:

(i) Sequence characteristics:

(A) Length: 1068 base pairs (B) Type: nucleic acid (C) Chain: double (D) Topology: circular

(Ii) Molecule type: DNA (genomic) (iii) Hypothetical: NO ——

- (iv) Antisense: NO '(vi) Original Source:

(A) Organism: Helicobacter pylori (ix)

Name / Key:. misc_charakter (B) Location: 1 ... 1068 (xi) Description of Sequence: SEQ ID NO: 32:

ATGAATATCA AAATTTTAAA AATATTAGTT GGAGGGTTAT TTTTTTTGAG CTTGAACGCC CATTTATGGG GGAAACAAGA CAATAGCTTT TTAGGGATTG GTGAAAGAGC CTATAAAAGC GGGAATTATT CTAAAGCGGC GTCTTATTTT AAAAAAGCAT GCAACGATGG GGTGAGTGAA GGCTGCACGC AATTAGGAAT CATTTATGAA AACGGGCAAG GCACTAGAAT AGATTATAAA AAAGCCCTAG AATATTATAA AACCGCATGC CAGGCTGATG ATAGGGAAGG GTGTTTTGGC TTAGGGGGGC TTTATGATGA GGGTTTAGGC ACGGCTCAAA ATTATCAAGA AGCCATTGAC GCTTACGCTA AGGCATGCGT TTTAAAACAC CCTGAGAGTT GCTACAATTT AGGCATCATT TATGATAGAA AAATCAAAGG CAATGCCGCT CAAGCGGTTA CTTACTATCA AAAAAGCTGT AATTTTGATA TGGCTAAGGG GTGTTATATT TTAGGCACTG CCTATGAAAA AGGCTTTTTA GAAGTCAAAC AGAGCAACCA TAAAGCCGTT ATCTATTATT TGAAAGCGTG GCGCTTTAAA CAATTCTGGT GGTTGCGCGA GTTTAGGCTC TATGTATATG TTGGGCÁGGT ATGTTAAAAA AGACCCCCAA AAGGCTTTTA ACTATTTCAA GCAAGCATGC GATATGGGGA GCGCGGTGAG TTGCTCTAGG ATGGGCTTTA TGTATTCGCA AGGGGACACT GTTTCAAAAG ACTTGAGGAA AGCCCTTGAT AATTATGAAA GAGGTTGCGA TATGGGCGAT GAAGTGGGTT GCTTCGCTCT AGCGGGCATG TATTACAACA TGAAAGATAA AGAAAACGCC ATAATGATTT ATGACAAGGG CTGTAAATTG GGCATGAAAC AGGCATGCGA AAATCTCACC AAACTCAGGG GGTATTAG (2) Information for SEQ ID NO: 33:

(i) Sequence characteristics:

(A) Length: 582 bp (B) Type: nucleic acid (C) String: double (D) Topology: circular (ii) Molecule type: DNA (genomic) (iii) Hypothetical: NO (iv) Antisense: NO ( (vi) Original source:

(A) Organism: Helicobacter pylori

120 íao

240

300

360

420

480

540

600

660

720

780

840

900

960

1020

1068

(ix) Features:

(A) Name / key: Mission character (B) Location: 1 ... 582 (xi) SEQUENCE DESCRIPTION: SEQ ID ATGAAAGAAA AAAACTTTTG GCCTTTAGGA ATCGTGGTGT TTTTAGTGGT GTTTGCCCTA .TTCAAGGGTC ATAACGAAGT GGATTTAAAC TTTAAATCCA ATTATCGTTT TTCAGTGGGT CCCATTTTGC CCTATTTTTC TAAAGGCACG TTAAACAACG CTTTGATTTT AGAAAAGTCC AAACCCGCTT TAGATTCGCC AAftTaTT \ \ CAGCCCAGAT TATTAGGAAC GCTTGATTGT TTGTTAGAGG GCGAŤAAAGT GGGGCGCTAT AAAGAAGAAT TGATTTTGGA GCAACTGGCT

NO: 33:

ATCATGAGCG TGCTTATTTT TGGGCTTGGG aaaaattcgc.ctaaaaatga TTTAGTGTAT TTTAACGCCA TGCTTAAAAC TTATGAAAAC TTAAAGCCTC. TTACCGAAAG CCCTAAAACC CATGGGGATAAAAAAATCCA AGAAAACCTT AACACGCTTT ATGCACAATT GCAACCGCTC GTGTATTTAG CGTTCTATCC CAGCCAATCC AAAAACGCAT

42Ό ^-

480

540

(2) Information for SEQ ID NO: 34:

(i) Sequence characteristics:

(A) Length: 870 pairs of bases (B) Type: nucleic acid (C) String: double,.

(D) Topology: circular <

(ii) Molecule type: DNA (genomic) (iii) Hypothetical: NO (iv) Antisense: NO (vi) Original source:

(A) Organism: Helicobacter pylori (ix)

(A) Name / Key: misc_charakter (B) Location: 1 ... 870 (xi) Sequence Description: SEQ ID NO: 34:

TTGGGTATCA ATATGTGTTC TTAAGCTTGT GCGCTGAAGA GAAGAAAACA CCCCTAAAGA GAGCTTAAAG AAGAAAATGA ATCCATAAGA AAAAACGCCA TCCATCTTAT TCCAACAAAT GGCGATATAG GGATTAACGCT GCTTCTCTCT

TAAAAAAATA AGAAATCTCA AAATATCACC AAAGAAAACA CGCTCCCATT CTTTTGGAAG AGTGGCAAAA AAGATTGATG GCTTTACATG CTCAAAGGGG GGCTAAAAAT AAGAGCGGCT TAATCCTTAT GAGAAGTTTG

TTTTATGCTT TGGTTTTATT TGACTGAAAC GAACACGACT AAAAACGCGC CCAAACTCTA AAAAAAGCCT GCTTGAAGAA AATTGCATGA AAAGAATGAA TTTTTATAGG CGTGATCCTT AACTTTTAAG CAATATTGC TATATGT

120

180

240

300

360

420

480

162 9 '9 · ·' '' '' '' '' '' '' '' '' '' '' '' '' '' ···· · About · ·· · «

AGCGCCTTAC GCTTTTATGG GGAATATTTA GGGGGGGCGA TCTTTAGCTT CTTATCAAAC CGCAAGCTTG AATATTGATC GACAAAGAAA AAAGGTTTGC GTTAGGGATA TTTGGAGGCG ATGTATCAAA ATTTAAAAGA GATTAGAGGG TATTCACAGC TTAAATTTAG GGGTGAGCAT GACGCTCAAC CTCAAACACC ATGCCTCCCT ... TAAAAGAAAC TTCGCAAACC ŤTTTTATATT TATTATATTA 'GTTACAACTA .TTTATTGTAA

TGAAAGGGTT TAAAAGCGAT 540 TGTTGATGGA TAAGCCTATT 600 TTGGAGTGGG GTGGAATGGG 660 CTAACGCCTT TGGGTTGGTG 720 GCTTTGAATT

370 (2) Information for SEQ ID NO: 35:

(i) Sequence characteristics:

(A) Length: 2007 pairs (B) Type: nucleic acid __ (C) String: double _______________________ (D) Topology: circular (ii) Molecule type: DNA (genomic) (iii) Hypothetical: NO (iv) Antisense: NO (vi) Original source:

(A) Organism: Helicobacter pylori (ix)

(A) Name / Key: misc_charakter (B) Location: 1 ... 2007 (xi) Description of Sequence: SEQ ID NO: 35:

ATGAGAAAAC TATTCATCCC ACTTTTATTA TTCAGCGCTT TAGAAGCGAA CGAGAAAAAC 60

GGCTTTTTCA TAGAAGCCGG CTTTGAAACT GGGCTATTAG AAGGCACACA AACGCAAGAA 120

AAAAGACACA CCACCACAAA AAACACTTAC GCAACTTACA ATTATTTACC CACAGACACG 180

ATTTTAAAAA GAGCGGCTAA TTTATTCACC AATGCCGAAG CGATTTCAAA ATTAAAATTC 240

TCATCTTTAT CCCCTGTTAG AGTGTTGTAT ATGTATAATG GTCAATTAAC TATAGAAAAC 300

TTCTTGCCTT ATAATTTAAA TAATGTTAAG CTTAGTTTTA CAGACGCTCA AGGCAACACG 360

ATTGATCTAG GCGTGATAGA GACCATCCCC AAACACTCTA AGATTGTTTT ACCCGGGGAG 420

GCGTTTGATA GTTTAAAAGA GGCGTTTGAT AAAATTGACC CCTATACTTT ATTTCTTCCA 480

AAATTTGAAG CCACTAGCAC TTCTATTTCT GATACTAACA CGCAGAGGGT GTTTGAAACG 540

CTCAATAACA TTAAAACAAA TCTTATAATG AAATATAGTA ATGAAAATCC AAACAATTTC 6 00

AACACTTGTC CTTACAATAA TAATGGTAAT ACAAAAAATG ATTGTTGGCA AAATTTCACC 660

CCACAAACCG CAGAAGAATT CACCAATTTA ATGTTGAACA TGATCGCTGT CTTAGACTCC 720

CAATCTTGGG GCGATGCGAT CTTAAACGCT CCTTTTGAAT TCACTAACAG CTCAACAGAT 780

TGCGATAGCG ATCCTTCAAA ATGCGTAAAT CCCGGAGTAA ATGGGCGTGT TGATACTAAA 840

GTCGATCAAC AATATATACT CAACAAACAA GGTATTATTA ATAATTTTAG AAAAAAAATA 900

GAAATTGATG CGGTTGTTTT AAAAAATTCA GGGGTTGTAG GGTTAGCCAA TGGATATGGC 960

AATGATGGTG AATATGGCAC ATTAGGGGTA GAAGCCTATG CTTTAGATCC TAAAAAACTC 1020

TTTGGCAACG ACCTTAAGAC TATCAATTTA GAAGATTTAA GAACCATCTT GCATGAATTC 1080

AGCCACACTA AAGGCTATGG GCATAACGGG AATATGACCT ATCAAAGAGT GCCGGTAACG 1140

AAAGATGGTC AAGTGGAAAA GGATAGTAAT GGCAAGCCAA AAGATTCTGA TGGCCTCCCC 1200

TATAATGTGT GTTCGCTTTA TGGGGGATCC AATCAGCCCG CTTTCCCTAG CAACTACCCT 1260

AATTCCATCT ATCACAATTG TGCGGATGTC CCGGCTGGCT TTTTAGGGGT AACAGCAGCG 1320

163 • · · φ '· ·

GTTTGGCAGC AGCTCATCftA TCAAAACGCC TTGCCGATCA ACTACGCTAA CTTGGGGAGT CAAACAAACT ACAACCTAAA CGCTAGTTTA AACACGCAAG ATTTAGCCAA TTCCATGCTC AGCACCATCC AAAAAACCTT TGTAACTTCT AGCGTTACCA ACCACCATTT TTCAAACGCA TCGCAAAGTT TTAGAAGCCC TATTTTAGGG GTTAACGCTA AAATAGGCTA TCAAAACTAC TTTAATGATT TCATAGGGTT GGCTTATTAT GGCATCATCA AATACAATTA CGCTAAAGCT GTTAATCAAA AAGTCCAGCA-ATTGAGCTAT GGTGGGGGGA TAGAŤTTGTT .. ATTGGATTTC 'ATCACCACTT ACTCCAATAA AAATAGCCCT. ACAGGCATTC.AAACCAAAAG GAATTTTTCT -TCATCTTTTG GTATCTTTGG GGGGTTAAGG GGCTTGTATA ACAGCTATTA TGTGTTGAAC: AAAGTCAAAG GAAGCGGCAATTTAGATGTG GCTACCGGGT TGAACTACC. CTATAAGCAT TCTAAATATT · CTGTAGGGAT. TAGCATCCCT TTAATCCAAA GAAAAGCTAG: CGTCGTTTCT »AGCGGTGGCG-ATTATftCGAA” CTCTTTTGTT TTCAATGAAG 'GGGCTAGCCA' CTTTAAGGTG. TTTTTCAATT ACGGGTGGGT GTTTTAG (2) Information for SEQ ID NO: 36:

(i) Sequence characteristics:

(A) Length: 192 pairs (B) Type: nucleic acid (C) String: double (D) Topology: circular (ii) Molecule type: DNA (genomic) (iii) Hypothetical: NE 7 '(iv) Antisense: NO '' (vi) Original source:

(A) Organism: Helicobacter pylori (ix)

(A) Name / Key: misc_charakter (B) Location: 1 ... 192 (xi) Sequence Description: SEQ ID NO: 36:

ATGAATACAG AAATTTTAAC CATCATGTTA GTTGTCTCCG TGCTTATGGG ATTGGTAGGC TTAATAGCGT TTTTATGGGG GGTTAAAAGC GGTCAGTTTG ACGATGAAAA ACGCATGCTT

1380

1440

1500

1560

1620

1680

1740

1800 '1860

1320

1980

2007

120

180

192 (2) Information for SEQ ID NO: 37:

(i) Sequence characteristics:

(A) Length: 1221 base pairs (B) Type: nucleic acid (C) String: double f-o4 (Č). String: double ', (D) Topology: circular.

(ii) Molecule type: DNA (genomic) (iii) Hypothetical: NO (iv). Antisense: NO (vi) (ix)

Original, source:

(A) Organism: Helicobacter pylori

Properties:

(A) Name / Key: misc_charakter (B) Location: 1 ... 1221 (xi) Description of Sequence: SEQ ID NO: 37:

ATGGTATTTT

TTATTCCATT

CTTTTAGTGG

AACCATATCC

GAAATCCAAA

GCCCTTATCC

TTTTTAGACT

CAAACTTCGC

TTGATGAACG

GCTATCGTTT

ATGGCGATGG

TATTACGATT

ACCCGCATTT

CCTCATTACG

GGCCGTGTGG

AATGAATTGC

TCGTTCGTTA

CCGCATTTGC

CGCACCGCTA

TATTCTAAGC

TATCTTTTAG

TTCATAAGAA

TATCCTATGG

GTGAAAGGCT

CCCAAAAACT

GCAATGTTAC

CTATTAGCCA

TTATCCCCAT

CCTATCAAGA

CGTATAAAAA

ATACAAGGGA

TTAGCTCTCG

CAAAAGCGCA

CTTCGCCTTT

GCGTGGATTA

GTTTTATAGG

GCTTGGTGTA

AAAAAGGGCA attttggcgt

AAAGCAAGCT

AAAAATTAGA

AGGGTTTTTA

AATTATTTTA

GGTTCTTTTA

TGTGTGGGAT

CTACTACAAT

CTACTACACT

GGATTTGCAA

TGTTTTCACT

TATTGTCAAA

AAGCGTGCCT

TTATCGTGTG

TTTGCACCAA

AGAAGTGGCA

TTCGTATGGG

TGCGGCTAAA

GGTTAAGGCG

TGCTCACATG

AATCATAGGA

GTATAAAAAC

GCATGGCAAA

AGAACTTTTT

AND

AATTTTATCT.

AAAGCCGATG

AAGCTCACGC

TTGAGCTCTC

TTAAGAGATG

ATCCATATTT

CGTAAAGAAA

GCCACCAATG

TTTAAACGCC

GGGCAAGCGT

TACTATCTTT

GGGTTTTTAC

AGGTTCCATC

CATGGCAGTT

GGTTATGGGA

AGCGCGTTCG

AGAGTGGGAA

TCCCGCCCCA

CAAAGAGAGG

AAAACCCATT

ATTCTTTAAT GGTTGCTTTT 60 GAATGGCTAA AAAGCAAACT 120 TGTTAGGGTT TTTAGAAAAA 180 AAGATAAAGA attgagtgct 240 CAAATÁACAC gctcattcaa 300 ACAAAAAAGG agaggattat 360 GAACCCTCCT TCTTTCCTTA 420 ACCCCCTTTT AGCCAACCAA 480 TAGTGAAAAA CGATAAAATC 540 TTGGCCAGCC GACCATCAAA 600 TTTCCCATTC AAACGGGCGT 660 TAGAAACCCC GGTGAAATAC 720 CTGTTTTAAA AGTTAAACGG 780 TGATCCATTC TGCTTCAGAC 840 AGGTGGTTGA aatccatttg 900 CTAACGGATT AAAAAAAGGC 960 GCACGGGTTT AAGCACCGGG 1020 TTAATCCTTT AGGCTATATC 1080 TTTTTTTAGA AAAAGCTCAG 1140 CTTTTGAAAA AAATTCATTT 1200 1221

(2) Information for SEQ ID NO: 38:

(i) Sequence characteristics:

(A) Length: 891 base pairs (B) Type: nucleic acid (C) String: double (D) Topology: circular (ii) Molecule type: DNA (genomic) ····

165 (iii) Hypothetical: NO (iv) Antisense: NO (vi) Original Source:

(A) Organism: Helicobacter pylori (ix)

(A) Name / Key: misc_charakter (B) Location: 1 ... 891 (xi) Sequence Description: SEQ ID NO: 38:

TTGTTTTTAG TCAAAAAAAT AGGCGTGGTA ATAATGATTT TAGTCTGCTT TTTAGCTTGC 60 TCGCAAGAGA-GCTTTATCAAVAATGCAAAAA AAAGCCCAAG AGCAAGAAAA

AAACGCCCCA GCTATGTGGA TTCGGATTAT GAAGTCTTTA GCGAAACGAT TTTTTTACAA 180 AACATGGTGT ATCAGCCTAT AGAGGAAAGA AACGCTTTTT TCCAACTGAC TAAAGATGAA 240 GACAATTCTT TTAACCCTGA AAATTCCGTG ATTTTACTGA ATGAGCCAAG CGATAATAGT 300 GAAAAAAACC TACTCTCATA CCCAAACGAT CCCAATAACA ATGAAGACAA CGCTAATAAT 360 AGTCAAAAAA ATCCGTTCCT TTACAAGCCC AAAAGAAAAA CAAAAAACCC AAAACTCATT 420 GAATATTCCC AACAAGATTT CTACCCCCTA AAAAATGGGG ATATTATCAT GAGTAAAGAA 480 GGGGATCAAT GGTTGATAGA AATCCAATCC AAAGCCTTGA AGCGTTTTTT AAAAGATCAA 540 AACGATAAAG ATCGCCAGAT CCAAACTTTC ACTTTTAATG ACACTAAAAC GCAAATCGCG 600 CAAATTAAGG GCAAAATTTC TTCGTATGTT TATACCACCA ATAACGGTAG CTTGAGTTTA 660 AGGCCTTTTT ATGAATCGTT TTTGTTAGAA AAAAAGAGCG ATAATGTTTA TACGATAGAG 720 AATAAGGCTT TAGATACTAT GGAGATTTCA AAGTGTCAAA TGGTGTTAAÁ AAAGCATTCA 780 ACCGATAAAT TAGACAGCCA GCATAAAGCC ATCAGTATTG ATTTGGATTT TAAAAAAGAG 840 CGCTTTAAGA GCGATACGGA ACTCTTTTTA GAATGTCTTA AGGAAAGTTA G 891 (2) Information for SEQ ID NO: 39:

(i) Sequence characteristics:

(A) Length: 747 bp (B) Type: nucleic acid (C) String: double (D) Topology: circular (ii) Molecule type: DNA (genomic) (iii) Hypothetical: NO (iv) Antisense: NO ( (vi) Original source:

(A) Organism: Helicobacter pylori (ix)

(A) Name / Key: misc_charakter (B) Location: 1 ... 747 (xi) Description of Sequence: SEQ ID NO: 39:

····

GTGAGCTATG ACAACACCGA TGATTATTAT TTCCCTAGAA ATGGGGTTAT CTTTAGTTCC

TATGCGACAA TGTCTGGTTT GCCAAGCTCT GGCACGCTCA AŤTCTTGGAA CGGGTTAGGC GGGAATGTCC GTAACACCAA AGTTTATGGT AAATTCGCCG CTTACCACCA TTTGCAAAAA TATTTATTGA TAGATTTGAT CGCTCGTTTT AAAACGCAAG GGGGCTATAT CTTTAGGTAT AACACCGATG ATTACTTGCC CTTAAACTCC ACTTTCTACA TGGGGGGCGT AACCACGGTG. .AGAGGCTTTA GGAACGGCTC AATCACACCT. AAAGATGAGT. TTGGCTTGTG GCTTGGAGGC: ~ GATGGGATTT TTACCGCTTC TACTGAATTG AGCTATGGGG TGTTAAAAGC GGCTAAAATG

... .CGTTTAGCGT .GGTTTTTTGA. CTTTGGTTTC. TTAACCTTTA; AAACCCCAAC. ..TAGGGGGAGT. .... '^ QTTCTATA'ACGCTCCCAC' CACGACGGCG ^? AATTTTAAAGIATTATGGCGT TGTAGGGGCT. GGGTTTGAAA GGGCGACTTG GAGGGCTTCT ACAGGCTTAC AGATTGAATG.GATTTCGCCC • ^; atggggcctt: tggtgttgat tttccctata GCGTTTTCAACCAATGGGG .cgatggcaat,; GGCAAAAAAT GTAAAGGGCT GTGGTTTAAC CCTAACATGA. ACGATTACAC 'GCAACATTTT' GAATTTTCTA TGGGAACAAG GTTTTAA (2) Information for. SEQ ID NO: 40:

120

180

240

300

360

420

480

540

600

660

720

747

- (- ij —history sequence ^ (A) Length: 1008 base pairs (B) Type: nucleic acid (C) String: double (D) Topology: circular (ii) Molecule type: DNA (genomic) (iii) Hypothetical: NO (iv) Antisense: NO (vi) Original Source: '(A) Organism: Helicobacter pylori (ix) Properties:

(A) Name / Key: misc_character (B) Location: 1 ... 1008 (xi) Sequence Description: SEQ ID NO: 40:

GTGCAACACT TCAATTTCCT CTATAAAGAT TCTTTATTTT CTATCGCTTT ATTCACTTTC ATTATCGCTC TTGTGATTTT ATTAGAACAG GCTAGAGCGT ATTTCACCCG AAAGAGAAAC AAAAAATTTT TGCAAAAATT CGCCCAAAAT CAAAACGCCT ATGCGAGCAG CGAGAATTTA GACGAGCTTT TAAAGCATGC TAAAATTTCC AGTTTGATGT TTTTAGCTAG GGCGTATTCT AAAGCGGATG TGGAAATGAG CATTGAAATC TTAAAAGGGC TTTTGAATCG CCCCTTAAAA GATGAAGAAA AAATCGCTGT TTTAGATTTA TTGGCTAAAA ATTATTTTAG CGTGGGGTAT TTGCAGAAAA CAAAAGACAC CGTGAAAGAA ATTTTGCGCT TTTCCCCAAG GAATGTGGAA GCGTTGTTGA AGCTTTTGCA TGCGTATGAA TTAGAAAAAG ATTATTCAAA GGCTTTAGAA ACTTTGGAAT GTTTGGAAGA ATTAGAGGTG CCTAAAATTG AAACGATTAA AAATTACCTC TATTTAATGC ATTTAATAGA GAATAAGGAA GATGCGGCTA AAATCTTGCA TGTTTCAAAA GCGTCGTTAG ATTTGAAAAA AATCGCTCTG AATCACTTAA AATCGCATGA TGAAAATCTT TTTTGGCAAG AAATTGATAC AACCGAACGG CTAGAAAATG TGATCGATCT TTTATGGGAT ATGAATATCC CTGCTTTTAT TTTAGAAAAA CATGCCCTTT TGCAGGACAT CGCGCGATCT CAAGGGTTGC TTTTGGATCA CAAACCTTGC CAAATTTTTG AATTAGAGGT TTTACGCGCT CTATTGCATA GCCCTATAAA AGCGAGTCTG ACTTTTGAAT ACCGCTGCAA GCATTGCAAA CAAATCTTTC CTTTTGAAAG CCATAGGTGT CCTGTGTGTT ACCAGTTAGC GTTTATGGAT ATGGTGCTTA AAATCTCTAA AAAAACGCAT GCTATGGGAG TGGATTAA

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720

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840

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960

1008 • i

167 ·· 9

(2) Information for SEQ ID NO: 41:

(i) Sequence characteristics:

(A) Length: 1242 bp (B) Type: nucleic acid (C) String: double (D) Topology: circular (ii) Molecule type: DNA (genomic) (iii) Hypothetical: NO

--- (iv) —Only -: - NO— ^J ------------------ (vi) Original source:

(A) Organism: Helicobacter pylori (ix)

(A) Name / Key: misc_character (B) Location: 1 ... 1242 (xi) Sequence Description: SEQ ID NO: 41:

ATGAGGAAAA TTTTTTCTTA TATTTCTAAG GTTCTATTAT TTATTGGGGT GGTTTATGCA GAGCCTGATT CTAAAGTGGA AGCCTTAGAA GGGAGGAAGC AAGAGTCTTC TTTGGATAAA AAAATCCGCC AAGAATTGAA GAGTAAGGAA TTGAAGAATA AGGAATTAAA GAATAAGGAT TTGAAAAATA AAGAAGAAAA GAAAGAAACA AAAGCCAAGA GAAAACCCAG AGCAGAAGTC CATCATGGGG ACGCCAAAAA TCCCACTCCA AAGATCACGC CTCCTAAAAT CAAAGGGAGT AGTAAGGGCG TTCAAAATCA AGGCGTŤCAA AACAACGCGC CAAAACCTGA AGAAAAAGAT ACAACCCCTC AAGCTACTGA AAAAAATAAG GAAACAAGCC CTAGCTCTCA ATTCAATTCC ATTTTTGGTA ATCCTAATAA CGCTACCAAC AACACCCTTG AAGATAAGGT CGTAGGGGGC ATTTCATTGC TTGTTAATGG TTCGCCTATC ACGOTGTATC AAATCCAAGA AGAGCAAGAA AAATCTAAAG TGAGTAAGGC TCAAGCTAGG GATCGTTTGA TCGCTGAACG CATTAAAAAC CAAGAAATTG AGCGCTTAAA AATCCATGTA GATGATGACA AGCTAGACCA AGAAATGGCG ATGATGGCGC AACAACAAGG CATGGATTTA GACCATTTCA AACAGATGCT TATGGCTGAG GGGCATTATA AACTCTATAG AGATCAACTT AAAGAGCATT TAGAAATGCA AGAATTGTTG CGTAATATTT TGCTCACGAA TGTGGATACC AGCTCTGAAA CCAAAATGCG CGAATATTAC AACAAACACA AGGAGCAATT CAGTATCCCC ACAGAAATAG AAACCGTGCG CTACACTTCC ACCAATCAA G AGGATTTAGA AAGGGCTATG GCAGACCCTA ATTTGGAAGT CCCAGGGGTG AGTAAGGCCA ATGAAAAAAT AGAGATGAAA ACCCTAAACC CTCAAATCGC CCAAGTCTTT

ATTTCGCATG AGCAAGGCTC TTTCACGCCC GTTATGAATG GGGGTGGGGG GCAGTTCATC ACCTTTTATA tcaaggaaaa aaggggtaaa aatgaagtga gcttcagtca ggccaagcaa TTCATCGCCC AAAAATTAGT GGAAGAATCT AAGGATAAGA TTTTAGAAGA GCATTTTGAA AAATTGCGCG TTAAGTCTAG GATTGTGATG ATCAGAGAGT GA (2) Information for SEQ ID NO: 42:

(i) Sequence characteristics:

(A) Length: 561 pairs of cravings

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1020

1080

1140

1200

1242

168 φ φ Typ Typ Typ Typ Typ Typ Β Β Β Β Β Β Β Β Β Typ · · · · · · · · · · · Β Β Β Β Β Β Β Β Β Β Β Β Β Β Β (iii) Hypothetical: NO (iv) Antisense: NO '(vi) Original Source:

(A) Organism: Helicobacter pylori ______ (ix) Properties: ____________________ (A) Name / Key: misc_character (B) Location: 1 ... 561 (xi) Sequence Description: SEQ ID NO: 42:

ATGATTAAAA GAATTGCTTG TATTTTAAGC TTGAGCGCGA GTTTAGCGTT AGCTGGCGAA SO GTGAATGGGT TTTTCATGGG TGCGGGTTAT CAACAAGGTC GTTATGGCCC TTATAACAGC 120 AATTACTCTG ATTGGCGTCA TGGCAATGAC CTTTATGGTT TGAATTTCAA ATTAGGTTTT 180 GTAGGCTTTG CCAATAAATG GTTTGGGGCT AGGGTGTATG GCTTTTTAGAVTTGGTTTAAC 240 ACTTCAGGGA CTGAACACAC CAAAACCAAT TTGCTCACCT ATGGCGGCGG: 300 TGGCGATTTG ATTGTCAATC TCATTCCTTT GGATAAATTC GCTCTAGGTC TCATTGGTGG- CGTTCAATTA 360 GCCGGAAACA CTTGGATGTT CCCTTATGAT GTCAATCAAA CCAGATTCCA GTTCTTATGG 420 AATTTAGGCG GAAGAATGCG TGTTGGGGAT CGCAGTGCGT TTGAAGCGGG CGTGAAATTC 480 CCTATGGTTA ATCAGGGTAG CAAAGATGTA GGGCTTATCC GCTACTATTC TTGGTATGTG 540 GATTATGTCT GATTTGTCT TCACTTTTTCTTTCTGTCT 56

(i) Sequence characteristics:

(A) Length: 729 bp (B) Type: nucleic acid (C) String: double (D) Topology: circular (ii) Molecule type: DNA (genomic) (iii) Hypothetical: NO (iv) Antisense: NO ( (vi) Original source:

(A) Organism: Helicobacter pylori (ix)

(A) Name / Key: misc_charakter (B) Location: 1 ... 729

• ·

169 (xi) Description of sequence: SEQ ID NO: 43:

ATGAAAAAAT TTTTTTCTCA ATCTTTGTTA 'GCTCTTATTAT.CTCTATGAA'. 'TGCGGTATCT 60 GGCATGGATG GTAATGGCGT TTTTTTAGGG GCGGGTTATT r

......- -CATGCGGATA TTAATTCTCA.AAAACAAGCC; ACCAACGCTA CGATCAAAGG. CTTTGACGCG 18 0 • CTCTTGGGGT 'ATACAATTTTT CTTTGAAAAA, CACTTTGGCT, TACGCCTTTA TGGGTTTTTT ·. 24 0 * GACTACGCTC. ATGCCAATTC TATTAAGCTT. AAAAACCCTA ACTATAATAG CGAAGCGGCG 300

CAAGTGGCTA GTCAAATTCT TGGGAAACAA GAAATCAATC GTTTAACAAA.CATTGCCGAT 360 CCCAGAACTT TTGAGCCGAA CATGCTCACT -TATGGGGGGG CTATGGACGT GATGGTTAAT 420 • GTCATCAATA TCATGGCTTÁ TGGCGACACC GAGCTTTGAG GGCATTTTAG. TGGAACAAGCCCTTGTGAGC 540

AAGAAAGCCA CTTCTTTCTC ATTTTTATTC AATGTGGGGG CTCGCTTAAG GATCTTAAAA 600

CATTCTAGCA TTGAAGCGGG CGTGAAATTC CCCATGCTAA AGAAAAACCC CTACATCACT 660

GCAAAAAATT TGGATATAGG GTTTAGGCGC GTGTATTCGT GGTATGTGAA TTACGTGTTC 720

ACTTTCTAG 729 (2) Information for SEQ ID NO: 44:

(i) Sequence characteristics:

(A) Length: 771 pairs (B) Type: nucleic acid (C) String: double (D) Topology: circular (ii) Molecule type: DNA (genomic) (iii) Hypothetical: NO. _t '/ (iv) Antisense: NO' (vi) Original Source:

(A) Organism: Helicobacter pylori (ix)

(A) Name / Key: misc_charakter (B) Location: 1 ... 771 (xi) Sequence Description: SEQ ID NO: 44:

ATGGGATACG CAAGCAAATT AGCTTTAAAG ATTTGTTTGG TAGGTTTATG TTTATTTAGC 60 acccttggtg cagaacacct tgagcaaaaa GGGAATTATA TTTATAAGGG AGAGGAGGCT 120 TATAATAATA AGGAATATGA GCGAGCGGCT TCTTTTTATA AGAGCGCTAT TAAAAATGGT 180 GAGTCGCTTG CTTATATTCT TTTAGGGATC ATGTATGAAA ATGGTAGGGG TGTACCTAAA 24 0 GATTACAAGA AAGCGGTTGA ATATTTCCAA AAAGCTGTTG ATAACGATAT ACCTAGAGGG 300 TATAACAATT TGGGCGTGAT GTATAAAGAG GGTAAGGGAG TTCCTAAAGA TGAAAAGAAA 360 GCGGTGGAAT ATTTTAGAAT AGCTACAGAG AAAGGTTATA CTAACGCTTA TATCAACTTA 420 GGCATCATGT ATATGGAGGG CAGGGGAGTT CCAAGTAACT ATGCGAAAGC GACAGAATGT 480 TTTAGAAAAG CGATGCATAA GGGCAATGTG GAAGCTTATA TTCTCCTAGG GGATATTTAT 540

170 • 444 • 4 * · 4 · 4 · 4 4 «4 4 · f

4444443 · 4 4

TATAGCGGGA

AAAATGGCGG

TATGGGTTAG

GATTTTGACA

ATGATCAATT

CTGATGTGAG

GCGTGGAAAA

TTGATAAAAA

GGGTATTGAG

TTCTTCTAGA

AGATAAAAAA

TTGTAAGAAA

CCGGACAAAG

GCTTATGAAG

AAGGCTGAAG

AAGAACACTT

ATAAGGCTGT

GGTTGTCAGA

AATACATGCA

CAAGCCGATA

TGTCTATTAT

GTCTTATCGG

AAAAGCATGC

AND

600

660

720

(2) Information for SEQ ID NO: 45:

(i) Sequence characteristics:

(A) Length: 1974 pairs (B) Type: nucleic acid (C) String: double (D) Topology: circular (ii) Molecule type: DNA (genomic) (iii) Hypothetical: NO (iv) Antisense: NO ( (vi) Original source:

(A) Organism: Helicobacter pylori (ix)

(A) Name / Key: misc_character (B) Location: 1 ... 1974 (xi) Sequence Description: SEQ ID NO: 45:

ATGAGAAAAC TATTCATCCC ACTTTTATTA GGCTTTTTCA TAGAAGCCGG CTTTGAAACT AAAAGACACA CCACCACAAA AAACACTTAC ΑΤΤΤΓΑΑΑΑΑ GAGCGGCTAA TTTATTCACC TCATCTTTAT CCCCTGTTAG AGTGTTGTAT TTCTTGCCTT ATAATTTAAA TAATGTTAAG ATCGATCTAG GCGTGATAGA GACTATCCCC GCATTTGATA GTCTAAAAAT TGACCCCIAT AGCACTTCTA TTTCTGACGC TAACACGCAG ACAAATTTGG TCGTAAATTA TAGGAATGAA GAAGCCTTTA CCCCACAAAC CGCAGAAGAA GTTTTAGACT CCCAATCTTG GGGCGATGCG AGCCCAACAG ATTGCGATAA TGATCCTTCA GTCAATTCTA AAGTCGATCA AAAATATGTG AAAAACAAAG CGGATCTTGA TGTAATTGTT AGTGATATTA CCCCTAGCAA CAATGATGAT GCTTCTGCTT TAGATCCTAA AAAACTCTTT GATTTAAGAA CCATCTTGCA TGAATTČAGC ATGACCTATC AAAGAGTGCC GGTAACGAAA AAGCCAAAAG ATTCTGATGG CCTCCCCTAT CAGCCCGCTT TCCCTAGCAA CTACCCTAAT GCTGGCTTTT TAGGGGTAAC AGCAGCGGTT CCGATCAACT ACGCTAACTT GGGGAGTCAA ACGCAAGATT TAGCCAATTC CATGCTCAGC GTTACCAACC ACCATTTTTC AAACGCATCG AACGCTAAAA TAGGCTATCA AAACTACTTT ATCATCAAAT ACAATTACGC TAAAGCTGTT

TTCAGCGCTT TAGAAGCGAA CGAGAAAAAC 60 GGGCTATTAG AAGGCACACA AACGCAAGAA 120 GCAACTTACA ATTATTTACC CACAGACACG 180 AATGCCGAAG CGATTTCAAA ATTAAAATTC 240 ATGTATAATG GTCAATTAAC TATAGAAAAC 300 CTTAGTTTTA CAGACGCTCA AGGCAATGTG 360 AAACACTCTA AGATTGTTTT GCCCGGAGAG 420 ACTTTATTTC TTCCAAAAAT TGAAGCCACT 480 AGGCTGTTTG AAACGCTCAA TAAGATTAAG 540 AACAAATTTA AAGATCACGA AAATCATTGG 600 TTCACTAATT TAATGTTGAA CATGATCGCT 660 ATCTTAAACG CTCCTTTTGA GTTCACTAAC 720 AAATGCGTAA ATCCTGGGAC AAACGGGCTT 780 TTAAACAAAC AAGACATTGT CAATAAATTT 840 TTAAAGGATT CAGGGGTTGT AGGGCTTGGG 900 GGCAAGCATT ATGGCCAGTT AGGGGTAGTA 960 GGCGATAACC TTAAGACTAT CAATTTAGAG 1020 CACACTAAAG GCTATGGGCA TAACGGGAAT 1080 GATGGTCAAG TGGAAAAGGA TAGTAATGGC 1140 AATGTGTGTT CGCTTTATGG GGGATCCAAT 1200 TCCATCTATC ACAATTGTGC GGATGTCCCG 1260 TGGCAGCAGC TCATCAATCA AAACGCCTTG 1320 ACAAACTACA ACCTAAACGC TAGTTTAAAC 1380 ACCATČCAAA AAACCTTTCT AACTTCTAGC 1440 CAAAGTTTTA GAAGCCCTAT TTTAGGGGTT 1500 AATGATTTCA TAGGGTTGGC TTATTATGGC, 1560 AATCAAAAAG «CCAGCAATT GAGC TATGGT 1620

171

* 0 · ♦ ·· · ♦ ♦: '·> 9 ·· · · ···

GGGGGGATAG ATTTGTTATT GGATTTCATC ACCACTTACT CCAATAAAAA TAGCCCTACA 1680 GGCATTCAAA CCAAAAGGAA, TTTTTCTTCA TCTTTTGGTA TCTTTGGGGG GTTAAGGGGGCC 1740 TTGTATGA GC 1740 TTGTATG ACCGGGTTGA.‘ACTACCGCTA .TAAGCATTCT AAATATTCTG TAGGGATTAG CATCCCTTTA 1860 .ATCCAAAGAA AAGCTAGCGT CGTTTCTAGC GGTGGCGATT / ATACGAACTC .TTTTGTTTTC 1920; 'AATGAAGGGG CTAGCCACTT ..TAAGGTGTTT TTCAATTACG.GGTGGGTGTT TTAG' 1974 (2) Information for SEQ ID NO: 46:

(i) Sequence characteristics:

(A) Length: 504 bp (B) Type: nucleic acid (C) String: double (D) Topology: circular (ii) Molecule type: DNA (genomic) (iii) Hypothetical: NO.

(iv) Antisense: NO '(vi) Original Source:

(A) Organism: Helicobacter pylori · (ix) Properties:

(A) Name / Key: misc_character (B) Location: 1 ... 504 (xi) Sequence Description: SEQ ID NO: 46:

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

(i) Sequence characteristics:

(A) Length: 885 base pairs (B) Type: nucleic acid (C) String: double (D) Topology: circular

172

(ii) Type of molecule:

(iii) Hypothetical:

(iv) Antisense:

DNA (genomic)

NO (iv)

NO (vi) Original source: '(A) Organism:' Helicobacter pylori (ix) Properties:

(A) Name / Key: misc_charakter. (B) Location: 1 ... 885_______________________ (xi) Description of sequence: SEQ ID NO: 47:

ATGAGTAATC AAGCGAGCCA TTTGGATAAT TTTATGAACG CTAAAAATCC CAAAAGTTTT 60

TTTGATAATA AGGGGAATAC CAAATTCATC GCTATCACAA GCGGTAAGGG GGGCGTGGGG 120

AAATCCAACA TTAGCGCTAA TTTAGCTTAC TCTTTATACA AGAAAGGTTA TAAGGTAGGG 180

GTATTTGATG CGGATATTGG TTTAGCGAAT TTAGATGTCA TTTTTGGGGT GAAAACCCAT 240

AAAAATATCT TGCATGCCTT AAAAGGCGAA GCCAAATTGC AAGAAATCAT 'TTGCGAGATT 300

GAACCCGGGC TTTGCTTAAT CCCTGGGGAT AGCGGCGAAG AAATTTTAAA ATACATCAGC 360

GGCGCGGAAG CTTTGGATCG ATTCGTAGAT GAAGAGGGGG TTTTAAGCTC, TTTAGATTAT 420

ATTGTGATTG ATACGGGTGC TGGGATTGGG GCCACTACGC AAGCGTŤTTT 'GAATGCGAGC 480 GATTGCGTGG TGATTGTTAC CACACCCGAT CCTTCAGGGA TTACCGATGC GTATGCATGC 540 ATTAAAATCA ACTCCAAGAA TAAAGATGAA TTGTTCCTTA TCGCTAACAT GGTAGCCCAA 600 CCTAAAGAAG GCAGGGCGAC TTATGAAAGG CTATTCAAGG TGGCTAAAAA CAATATCGCT 660 TCATTAGAAT TGCACTATTT AGGGGCGATT GAAAACAGCT CCTTATTGAA ACGCTATGTG 720 AGGGAGCGAA AGATTTTGAG GAAAATAGCC CCTAACGATT TGTTTTCGCA ATCCATTGAC 780 CAGATAGCGA GCCTTTTAGT TTCTAAACTA GAAACCGGCA CTTTAGAAAT ACCAAAAGAA 840 GGTTTAAAAA GCTTTTTTAA AAGGCTTTTG AAGTATTTGG GGTAG 385 (2) Information for SEQ ID NO: 48:

(i) Sequence characteristics:

(A) Length: 1119 pairs (Β) Type: nucleic acid (C) String: double (D) Topology: circular (ii) Molecule type: DNA (genomic) (iii) Hypothetical: NO (iv) Antisense: NO ( (vi) Original source:

(A) Organism: Helicobacter pylori

173

• ·· 99 9 ·· 9 9 9 9 9999 98 99 9 9 • • 9 9 9 9 9 99 999 99 9 • 9 9  9 9 9 • • 99 · 999 • 9 9 '' 9 '· 9 Sep

(ix) Features:

(A) Name / Key: misc_charakter (B) Location: I ... 1119 (xi) Sequence Description: SEQ ID NO: 48:

TTGGAACCTT CAAGAAATCG CCTAAAACAT GCCGCCTTTT TTGTGGGGCT TTTTATCGTT 60

TTGTTTTTAA TTATAATGAA GCACCAAACC TCCCCCTATG 'CTTTCACGCA TAATCAAGCC 120

CTTGTCACTC AAACCCCCCC CTATTTCACG CAACTCACTA TCCCTAAACC AAATGACGCT 180

TTAAGCGCGC ATGCGAGCTC TTTAATCAGC TTGCCTAACG ACAATCTTTT'GAGCGCTTAT 240

TTTAGCGGCA CTAAAGAAGG GGCAAGGGAT GTGAAAATCA GCGCGAATCT TTTTGACAGC 3 00

AAGACTAATC GCTGGAGCGA AGCCTTCATT CTTTTAACCA AAGAAGAGCT TTCTCATCAT 360

TCGCATGAAT ACATCAAAAA ATTAGGTAAC CCCTTGCTTT TTTTGCATGA TAATAAAATT 420 ~ TTGTTGTTTG ~ TCGTAGGGGT GAGCATGGGC GGGTGGGCCA CTTCTAAAAT CTATCAATTT 480 GAAAGCGCTT TAGAGCCGAT TCATTTTAAG TTTGCGCGAA AACTCTCTTT AAGCCCTTTT 540

TTAAATTTGA GCCATTTAGT AAGGAATAAG CCTTTAAACA CCACTGATGG. .CGGGTTTATG 600

CTACCACTCT ATCACGAATT AGCCACCCAA TACCCCTTGT TGTTGAAATT TGACCAACAA 660

AATAACCCAA GAGAGCTTTT.AAGGCCTAAT ACCTTAAACC ACCAGCTCCA ACCAAGCTTA 72 0 ACCCCCTTTA AAGACTGCGC TGTCATGGCG TTTAGAAACC ATTCTTTTAA AGATAGCCTC 780

ATGCTAGAAA CCTGTAAAAC CCCCACTGAT TGGCAAAAAC CCATTTCTAC AAATCTTAAA 840

AACTTAGATG ATTCTTTAAA TTTACTCAAT TTAAATGGAA TATTGTATTT GATCCACAAC '900 CCTAG.CGATT TATCACTGCG TCGTAAAGAA CTTTGGCTTT CTAAATTAGA AAACTCCAAC 960 TCGTTTAAAA CCTTAAAAGT TTTGGATAAA GCGAATGAAG TGAGTTACCC AAGCTATAGC 1020 CTTAATCCGC ATTTTATAGA TATTGTCTAT ACTTACAACC GCTCTCATAT CAAACACATC .1080 CGTTTCAATA TGGCTTATTT AAATTCCCTT CTCAAGTGA 1119 (2) Information for SEQ ID NO: 49:

(i) Sequence characteristics:

(A) Length: 2937 pairs (B) Type: nucleic acid (C) String: double (D) Topology: circular (ii) Molecule type: DNA (genomic) (iii) Hypothetical: NO (iv) Antisense: NO ( (vi) Original source:

(A) Organism: Helicobacter pylori (ix)

(A) Name / Key: misc_charakter (B) Location: 1 ... 2937 (xi) · Sequence Description: SEQ ID NO: 49:

174 ⁽ 9 · · 0 0 0 ··· 9 9 ^{, f} 9 0 '· · 0 · 0 0; ··' · · - '· 10 9 .9. (0 0 0 0 0 00 0 0 000 '0 · · ·'<··>'··· ·· 0 ·· 00

ATGAAGAAAA GAAAACATGT ATCCAAGAAA GTGTTTAATG TCATTATCTT GTTTGTGGCA 60

GTATTCACTC TTTTAGTCGT CATTCACAAA ACCCTTTCAA ACGGCATTCA CATACAAAAT 120

TTAAAAATTG GAAAACTTGG CATTTCTGAA TTATACTTAA AACTCAATAA CAAGCTTTCT 180

TTGGAAGTTG AGCGGGTTGA TCTCTCTTCT TTCTTCCATC AAAAACCCAC TAAAAAGCGT 240

TTAGAAGTTT CTGATTTGAT TAAAAATATC CGTTATGGCA TTTGGGCGGT GTCTTATTTT 3 00

GAAAAACTTA AAGTCAAAGA AATCATTTTA GACGATAAAA ATAAAGCCAA TATCTTTTTT 360

GATGGGAATA AATACGAGTT AGAATTTCCA GGATATAAAG GGGAATTTTC CCTAGAAGAC 420 .GATAAAAATA TCAAGCTTAA AATCATCAAT. TTGCTTTTTA AAGATGTTAA AGTCCAAGTG 480 • GATGGCAACG ČCCACTATTC ACCCAAAGCC AGGAAAATGG 'CGTTCAATTŤ: GATTGTCAAG. 540. CCCTTAGTTG AACCCAGCGC TGCAATTTAT TTGCAAGGGC TAACCGATTT AAAAACCATA 600 / GAATTAAAAA TTAACACTTC TCCAATGAAA AGCCTAGCGT TTTTAAAGCC TCTTTTCCAA 660 “CGCCAATCGT AACAAAAATTT AAGATTGATA ACGCTTTAAT CAAGGCTAAT. TTCACTCCTA -GCGAGTTTAT CCCATCGCTT '780

TTGGAAAATT .CTGTAGTTAA, AGCCACTTTG ATTAGAGCTT .CAGTCGTTTT .TAATGATGGC 840 'TTATCGCCCA TTAAAATGGA TAAAACCGAA TTGATTTTCA AAAACAAACA GCTCCTCATA 900

CAGCCCCAAA AAATCACTTA 'TGAAACCATG GAATTAACCG GCTCTTACGC' CACTTTTTCC 960

AATTTGTTAG AAGCCCCTAA GTTGGAGGTT TTTTTAAAAA; CGACČCCTAA‘TTATTATGGC 1020 GATAGCATTA AGGATTTATT GAGCG.CTTAT AAAGTCGTTT TACCTTTGGA TAAAATCAGC 1080 ATGCCATCTA GCGCGGATTT GAAGCTCACT

CTTTACACGC AAAGCGCTCA AATCAATTTG GACATCGCCC AAGAATACCA ATACATCTAC 1250 ATAGACACGA TCCACACGCG CTATGCAAAC ATGCTGGATT TAGACGCTAA. AATCGCTTTA 1320 GATTTAGGTC AAAAAAACCT TTCTTTGGAT TCTTTAGTCC ATAAAATCCA AGTCflATACC 1380 AATAACAATA TCAACATGCG CTCTTATGAT CCCAATAACA CTCAAGAAGA TCCGCAAACT 1440 AACTTTACTT TGGATCTAAA AAGCTTGCAT TCTATCATTC AAGAGGGTGA AAATTCAGAA 1500 GTTTTTAGAA GAAAAATCAT AGACACCATT AAAGCCCAAA GCGAAGATAA ATTCACTAAA 1560 GATGTTTTTT ACGCCACAGG AGACACTCTC AAAAGCCTGT CGTTGAGTTT TGATTTTTCC 1620 AACCCCGATC ACATACAATG GAGCGTGCCA CAACTCTTAT ŤAGAAGGCGA ATTTAAAGAT 1680 AACGCCTATA CTTTTAAGAT CAAAGATTTG AAAAAGATCA AGCCCTATTC CCCCATTATG 1740 GACTATATTG CCCTAAAAGA CGGCTCTTTA gAggTŤTCTA CGAGCGATTT TGTCAATATT 1800 GATTTTTTTG CTAAAGATTT GAAAATGAAC CTCČCCATTT ATAGGAGCGA TGGATCGCAT 1860 TTTGATTCTT TTTCTTTATT TGGCTCTATC AATAAAGATG AAATTTCTGT CTATACTCCA 1920 AGCAAAAGCA TATCCATAAA AGTTAAGGGG GATCAAAAGG ATATTACCCT TAATAACATT 1980 GATTTGAGTA TTGATGATTT CTTGGATAGT AAAATGCCAG CTATTGCGGG ATTATTCTCA 2040 AAAGAACGAA AAGAAAAGCC TAGCTCTAAA GAAATCCAAG ATGAAGATGT TTTCATTAGC 2100 GCCAAACAAC GCTATGAAAA AGCCCACAAA ATTATCCCCA TCTCTACACG CA TCCATGCT 2160 AAAGATGTCG TGCTGATCTA TAAAAAAATG CCTTTTCCTT TAGAAAATCT TGATATTGTC 2220 GCTCAAGACG ATAGGGTGAA AATTGATGGC AATTATAAAA ACGCCATGAT CATGGCGGAT 2280 TTAGTGCATG GGGCTTTGTA TCTTAAGGCT CATAATTTTA GCGGGGATTA TATCAACACC 2340 ATTCTTCAAA AAGATTTCGT AGAAGGAGGC TTATTCACGC TTATTGGGGC TCTTGAAGAT 2400 CAGGTTTTCA ATGGCGAATT GAAATTCCAA AACACAAGCT TAAAGAATTT CGCCCTCATG 2460 CAAAACATGG TCAATCTCAT CAACACCATT CCCTCCCTCA TTGTCTTTAG AAACCCTCAT 2520 TTAGGGGCTA ATGGCTATCA AATCAAAACC GGCTCCGTTG TGTTTGGGAT CACTAAAGAA 2580 TATTTAGGGT TAGAAAAAAT TGATCTTGTC GGCAAAACGC TTGATATTGC TGGCAATGGA 2640 ATCATTGAAT TAGACAAAAA CAAATTAGAT TTAAACTTAG AAGTTTCCAC TATCAAGGCT 2700 TTGAGTAATG TCTTAAATAA AATCCCTATC GTGGGCTATC TCGTTTTAGG AAAAGGAGGT 2750 AAAATCACCA CTAACGTGAA TGTCAAAGGC ACGTTGGATA AGCCTAAAAC CCAAGTAACT 2820 TTAGCGTCAG ATATTATCCA AGCGCCTTTT AAAATCTTAC GCCGTATTTT CACGCCTATT 2880 GACATCATCG TGGATGAAGT CAAGAAAAAC ATTGATTCAA AAAGGAAATT AAAATGA 2937 ₍ «. <·. · »·

175> · ♦ * (2), Information for SEQ ID NO: 50:

(i) Sequence characteristics:

(A) Length: 1434 pairs of cravings; (B) Type: nucleic acid (C) String: double (D) Topology: circular (ii) Molecule type: DNA (genomic) (iii) Hypothetical: NO, (iv) Antisense: NO (vi) Original 'source :

(A) Organism: Helicobacter pylori (ix)

(A) Name / Key: misc_charakter (B) Location: 1 ... 1434 (xi) Description of Sequence: SEQ ID NO: 50:

ATGAATACTA TTATAAGATA TGCGAGTTTA TGGGGCTTGT GTATTACTCT .AACTCTWSCG CAAACCCCCT CTAAAACCCC TGATGAAATC AAGCAAATCC TTAACAATTA / TAGCCATAAG AATTTAAAGC TCATTGATCC GCCGACAAGT TCTTTAGAAG CGACACCGGG 'TTTTTTACCC TCGCCTAAAG AAACAGCGAC CACGATCAAT CAAGAGATCG CTAAATACCA TGAAAAAAGC GATAAAGCCG CTTTGGGGCT TTATGAATTG CTAAAGGGGG CTACCACCAA TCTCAGTTTG CAAGCGCAAG AACTCAGTGT CAAGCAAGCG ATGAAGAACC ACACCATCGC CAAAGCGATG TTTTTGCCTA CTTTGAACGC GAGTTATAAT TTTAAAAATG AAGCTAGGGA TACTCCAGAA TATAAGCATT ATAACACCCA ACAACTCCAA GCTCAAGTCA CATTGAATGT GTTTAATGGC TTTAGCAATG TGAATAATGT CAAAGAAAAG TCTGCGACTT ACCGATCCAC TGTGGCTAAT TTAGAATATA GCCGCCAAAG CGTGTATTTG CAAGTGGTGC AACAATACTA CGAGTATTTT AACAATCTCG CTCGCATGAT CGCTTTGCAA AAGAAATTAG AGCAAATCCA AACGGACATT AAAAGGGTTA CTAAGCTCTA TGACAAAGGG CTGACCACGA TTGATGATTT ACAAAGCTTA AAAGCGCAAG GGAATTTGAG CGAATACGAT ATTTTGGACA TGCAATTTGC TTTGGAGCAA AACCGCTTGA CTTTAGAATA CCTCACTAAC CTCAGTGTGA AAAATTTGAA AAAGACCACG ATTGATGCGC CTAATTTGCA ATTAAGAGAA AGGCAGGATT TGGTTTCTTT AAGGGAGCAG ATTTCTGC AC tcagatacca aaacaagcaa ctcaattatt accccaagat agatgtgttt GACTCATGGC TTTTTTGGAT CCAAAAACCC GCTTATGCCA CAGGGCGTTT TGGGAATTTC TACCCAGGTC AGCAAAATAC GGCTGGGGTT ACTGCGACTT TGAATATTTT TGATGATATA GGGTTGAGCT TGCAAAAACA ATCCATCATG CTAGGCCAAT TAGCGAATGA AAAGAATTTA GCGTATAAAA AATTGGAGCA AGAAAAAGAC GAACAGCTTT ACAGAAAGTC GCTTGATATT GCCAGAGCTA AGATTGAATC TTCAAAGGCT AGTTTGGATG CGGCCAATCT TTCTTTTGCC AATATTAAAA GGAAATACGA CGCTAATTTA GTGGATTTCA CTACCTATTT AAGGGGCTTA ACCACGCGCT TTGATGCAGA AGTGGCTTAC AATTTAGCGC TCAACAATTA CGAAGTGCAA AAAGCCAATT ACATTTTTAA CAGCGGGCAT AAAATAGACG ACTATGTGCA TTAA (2) Information for SEQ ID NO: 51:

(i) Sequence Characteristics:

»<*

176 '· 9 9 * 9 9 '99 9 9 .99 9 9

ÍB 9 ^f 9 Ů · ·. ·· ·. : 9> · · <9 '· 9 (.9 · * ι ·' · 9 9 * 9 '' 9 9 29 9 <Β · Β · ΒΒΒ · · · Β · · 9

V9 9 9 9999 99 - · · · (A) Length: 1239 base pairs (Β) Type: nucleic acid, (C) String: double (Dj Topology: circular (ii) Molecule type: DNA (genomic) (iii) Hypothetical : NO (iv) Antisense: NO (vi) Original Source:

----- (A) —Organism: —Helicobacter pylori ---------- (ix)

(A) Name / Key: misc_charakter (B) Location: 1 ... 1239 (xi) Description of Sequence: SEQ ID NO: 51:

ÉATGCTATCTT TTATAAGCGC GTTTGATAAA AGGGGCGTTT CAATACGCCT TCTAACAGCC 60 TTGTTACTGC TTTTTAGTTT GGGTTTGGCT AAAGATTTAG AAATCCAAAC TTTTGTGGCT 120 AAATACCTTT CTAAAAATCA AAAAATACAA GCCCTACAGG AGCAAATTGA CGCTTTAGAT 180 TCTCAAGAAA AAGTCGTTAG CAAATGGGAT AACCCTATTT TGTATTTAGG CTATAACAAC. 240 GCTAACGTGA GCGATTTTTT CAGGCTGGAT · AGCACCTTAA 'TGCAAAACAT GAGCTTGGGT 300 TTGTCTCAAA AAGTGGATTT AAATGGTAAA AAACTCACGCAGTCTAAAAT GATCAATTTA' 360 GAAAAACAAA AAAAAATATT AGAGCTTAAA AAAACCAAGC AGCAATTGGT GATTAATTTA 420 ATGATAAACG GCATTGAAAA CTATAAAAAC CAACAAGAAA TAGAGCTTTT AAACACAGCG 480 ATTAAAAATT TAGAAAACAC CCTCTATCAA GCČAACCATT CCAGTTCGCC CGATTTAATA 540 GCGATCGCCA AGTTAGAAAT TTTAAAATCG CTATTAGAAA TCCAAAAAAA CGATTTAGAA 600 GTAGCGCTCT CTAGCAGCCA TTATTCCATG GGCGAATTGA CTTTTAAAGA AAACGAGATT 660 TTAAGCATTG CCCCTAAAAA TTTTGAATTC AATAACGAGC AAGAGCTGCA TAACATTAGC 720 GCCACTAATT ACGATATTGC GATCGCCAGG CTTGATGAAG AAAAAGCACA AAAAGACATC 780 ACTCTGGCTA AAAAAAGCTT TTTAGAAGAC ATAAACGTTA CCGGGGTGTA TTATTTCCGC 840 TCCAAACAAT ACTATAACTA CGACATGTTT AGCGTCGCTT TGTCTATCCC TTTACCTCTT 900 TATGGCAAGC AGGCTAAATT AGTGGAGCAA AAGAAAAAAG AAAGCTTGGC GTTTAAAAGC 960 GAAGTGGAAA ACGCCAAAAA CAAAACGCGC CACCTGGCCC TAAAACTCCT TAAAAAATTA 1020 GAAACCTTGC AAAAAAACCT GGAATCGATC AATAAAATCA TCAAACAGAA. TGAAAAAATC 1080 GCGCAAATTT ATGCGCTTGA TTTGAAAACT AATGGCGATT ACAACGCTTA TTACAACGCC 1140 TTGAATGACA AAATCACTAT TCAAATCACC CAGCTTGAAA CCTTAAGCGC TCTAAATAGT 1200

(i) Sequence characteristics:

(A) Length: 414 pairs of basses (B) Type: nucleic acid (C) String: double (D) Topology: circular · · »'········· · · tt' · tt 'tt' tt Itt í · Tt tt · tt tttt · · · · · · · tt ·

177 (ii) Type of molecule: DNA (genomic) (iii) Hypothetical: NO (iv) Antisense: NO (vi) Original source:

(A) Organism: Helicobacter pylori (ix)

(A) Name / Key: misc_charakter

---------- (B) -Location -: - 1 — 7r414 --- (xi) Description of sequence: SEQ ID NO: 52:

ATGCGTATAG

GCGGATTTAG

CATAAAAACC

AAAAATAGCG

AAAAGCGATA

ATGCCGATTG

AGCAAAAAAA

TTAGAAATTT ATTTCTTGTA TCGTTTGTGG CGTATAGTAG TGCGTTCGCA AAACCGGAAC CAAAAACGAC AAAAAGAGCG GTAAAAAATT TTACAAACTC ATGGCTCAGA AACCGAGACT AAAAACGATA AAAAGCTTTA TGATTTCACT GATTAGAAGG CGTGGATTTA GAAAAAAGCC CTAACCTTAA AAGCCATAAA AAAAGTTTTA TAAACAACTC GCTAAAAACA ATATCGCTGA AGGGGTGAGC TGAATTTCAA TAAAGCCCTA TCTTTTGGGC CTTATTTTGA AAGGACTAAA CCCAATACAT GGACGGCGGG TTGATGATGC ACATCCGTTT TTAA

120

180

240

300

360

(2) Information for SEQ ID NO: 53:

(i) Sequence characteristics:

(A) Length: 930 pairs (B) Type: nucleic acid (C) String: double (D) Topology: circular (ii) Molecule type: DNA (genomic) (iii) Hypothetical: NO (iv) Antisense: NO ( (vi) Original source:

(A) Organism: Helicobacter pylori (ix)

(A) Name / Key: misc_charakter (B) Location: 1 ... 930 (xi) Sequence Description: SEQ ID NO: 53:

178 (9 · 9 ·) ·

TTGATGCCAC AAAACCAGCT TGTGATCACC AAATTTTCTA AAAATTTAAA ACGCAACCTC GTGGGGCTTG GCGTGGGGTT TTTAAAATTT GAGAGGAATG CGGTTTTAAG GGATTTTAGG AAAGAGATT GAAAACAAGCG; AAAGGGGGG GATTTAGAAA ATTTGAGCTT, AAATCAAAAA: ATGCCCCTAA; AAACTTATAG CGCTATCAAA; AAGATTAAGG.GCGTTGAATC CGGGATCGAT

-GCGAGCGCTG ATGGGATTGT GGATTTTGTG 'TTGGTGCGCA -TTGAACATGC GTTTGGTTTC

- AATGTGCAGC CTAAAAGCTT CATCCAAAAA GGTAATAGCG GCGGCGAAAA ATTGCATTAT GCAGAAAAAT TCCTAGCATG GGATTTGGAT

- TTTATTGAAT GGAAGAATCT GTTTTGGGTT GTGGATAAAG ACACCTTAAA AGGTCAGTAG

ATCATTGATG AATCAGGCTC TAAGCAACTC atcatttctg TTGTCATTCT TTTATTGATC TTAATCGCTA AAATGGATAC GATGACAAGC CGCCCTAGCG TTTATTGTGG GGCAAAAGAT. CCGTGGGCTA AATGGGGGAG'GGCATCTCTA TGATGAAGTG CATTTAGCAC TCATGCTCAT: TCCTAATGGC CCCACTAAAG 'AAAGGAACCA CCCCATTAAA TTTATCGCGC CATTGAACAC - GCCTGTGTAT AAGACTCGCAT. GTATGGGAAC AGCTCCATTT ATACGCACTT 'GATCATGTC GGGCAGTTGA / TTGGCTATAG CGGGAAGAGC GAAGTGCGGT. TTTTGGGTAA AATTTTAGAC cattttcaaa GCGCTTTAGA - AGAAAATAAA TTAGAAGACA TCGTCCAGCT CCAAGAGCAT

120 190 240 300 3 60 420 480 540 600 660 720 780 840 900 930 (2) Information for SEQ ID NO: 54:

(i) Sequence characteristics:

(A) Length: 999 bp (B) Type: nucleic acid (C) String: double (D) Topology: circular (ii) Molecule type: DNA (genomic) (iii) Hypothetical: NO (iv) Antisense: NO ( (vi) Original source:

(A) Organism: Helicobacter pylori (ix)

(A) Name / Key: misc_charakter (B) Location: 1 ... 999 (xi) Sequence Description: SEQ ID NO: 54:

GTGCTATATT TTTTAACCAG TTTATTTATT TGCTCTTTGA TTGTTTTGTG GTCTAAAAAA 60 TCTCATGCTCT TTGTGGATAA CGCTAATAAA ATCCAAGGCT TCCATCATGC AAGAACCCCA 120 CGAGCCTGTGTG GGCTTTTT

GAGATGCCTT TTAAGGGGCC TTTTGTTTTC TTAGGGCTAT CGCTAGTGTT TTTGAGCGGT 240 TTTTTAGAAG ACATTAACCT TTCATTAAGC CCCAAAATAC GCCTTATTTT GCAAGCTGTA 300 GGGGTCGTTT GCATCATTTC ATCAACGCCT TTAGTGGTGA GCGATTTTTC GCCCCTTTTT 360 AGCTTGCCTT ATTTCATCGC TTTTTTATTC GCTATTTTTA TGCTGGTGGG TATCAGTAAC 420 GCTATTAATA TCATTGACGG GTTTAACGGG CTTGCATCTG GGATTTGCGC GATCGCGCTT 480 TTAGTCATTC ATTATATAGA CCCTAGCAGT TTGTCTTGTT TGCTCGCTTA CATGGTGCTT 540 GGGTTTATGG TGTTAAATTT CCCTTCAGGA AAGATTTTTT TAGGCGATGG GGGGGCGTAT 600 TTTTTGGGTT TGGTGTGCGG GATTTCTCTC TTGCATTTGA GTTTGGAGCA AAAAATCAGC 660

179 ·· ···· · ·. · «• '· ·. ·' ·· <

·.....::::::::::::

GTGTTTCTTG ggctcaattt AATGCTTTAT CCGGTCATAG AGGTGCTTTT TAGTATGCTT 720 aggcgcaaaa 'taaaacgcca GAAAGCCACC atgccggata atttgcattt gcacaccctt 780 TTATTTAAAT TCTTGCAACA ACGCTCTTTC AATTACCCTA ACCCTTTATG CGCGTTTATC 840 CTTATTCTAT gcaacctgcc ttttatttta ataagcgttt tgtttcgctt GGACGCTTAT 900 GCGČTCATTG TGATTAGCCT AGTCTTTATČ GCATGCTATT TAATAGGCTA TGCTTATTTG 960 AATAGGCAAG TTTGCGCTTT AGAAAAGCGG GCGTTTTAA ^999' (2) Information for SEQ ID NO : 55:.

. (I) Sequence characteristics:

(A), Length: 816 bp (B) Type: nucleic acid (Č) String: double (D) ^- TopolOgler ^ circular ----— (ii) Molecule type: DNA (genomic) (iii) Hypothetical: NO (iv) Antisense: NO (vi) Original Source:, (A) Organism: Helicobacter pylori '(ix) Features:' (A) Name / Key: misccharacter '(B) Location: 1 ... 816 (xi) Sequence Description: SEQ ID NO: 55:

ATGAACATAT TCAAGCGTAT TATTTGCGTA ACCGCTATTG TTTrAGGTTT TTTTAACCTT 60 TTAGACGCCA AACACCACAA AGAAAAAAAA GAAGACCACA AAATCACTCG TGAGCTTAAA 120 GTGGGCGCTA ACCCTGTGCC GCATGCGCAA ATCTTGCAAT CAGTTGTGGA TGATTTGAAA 180 GAGAAAGGGA TCAAATTAGT GATCGTGTCT TTTACGGATT ATGTGTTGCC TAATTTAGCG 240 CTCAATGACG GCTCTTTAGA CGCGAATTAC TTCCAGCACC GCCCTTATTT GGATCGGTTT 300 AATTTGGACA GAAAAATGCA CCTTGTTGGT TTGGCCAATA TCCATGTGGA GCCTTTAAGA 360 TTTTATTCTC AAAAAATCAC AGACATTAAA AACCTTAAAA AAGGCTCAGT GATTGCTGTG 420 CCAAATGATC CGGCCAATCA AGGCAGGGCG TTGATTTTAC TCCATAAACA AGGCCTTATC 480 GCTCTCAAAG ACCCAAGCAA TCTATACGCT ACGGAGTTTG ATATTGTCAA AAATCCTTAC 540 AACATCAAAA TCAAACCCCT AGAAGCTGCG TTATTGCCTA AGGTTTTAGG GGATGTGGAT 600 GGGGCTATCA TAACAGGGAA TTATGCCTTG CAAGCAAAAC TCACCGGAGC CTTATTTTCA 660 GAAGATAAGG ACTCGCCTTA TGCTAATCTT GTAGCCTCTC GTGAGGATAA TGCGCAAGAT 720 GAAGCGATAA AAGCGTTGAT TGAAGCCTTA CAGAGCGAAA AGACCAGGAA ATTCATTTTG 780 GATACCTATA AGGGGGCGAT TATCCCGGCT TTTTAA ³¹⁶ (2) Information for SEQ ID NO: 56:

(i) Sequence characteristics:

'i

• 9 • 9

9

9 9

180

9 · I »··

9 9

9 ·

9 9

9 9

9 9 · * (A) Length: 951 pairs of flanks.

Type: nucleic acid (C) String: double (D) Topology: circular (ii) Molecule type: DNA (genomic) (iii). Hypothetical: NO (iv) Antisense: NO (vi) Original Source:

(A) Organism: Helicobacter pylori______ (ix) Features: ´ (A) Name / Key: misc_charakter (B) Location: 1 ... 951 (xi) Sequence Description: SEQ ID NO: 56:

ATGCAAGAAT TCAGTTTGTG GTGCGATTTT ATAGAAAGGG ATTTTTTAGAAAACGATTTT 60 TTAAAGCTCA TCAATAAGGG GGCTATTTGC GGGGCGACGA GTAACCCTAG .TTTGTTTTGC 120 GAAGCGATCA CAAAAAGCGC GTTTTATCAA GATGAAATCG CTAAACTCAA / AGGCAAAAAA 180 GCTAAAGAAA TTTATGAAAC TCTGGCACTA AAGGATATTT. TACAAGCCTC / TAGCGCGTTA 24 0

ATGCCTTTGT ATGAAAAAGA CCCTAACAAC GGCTACATCA GCCTAGAAAT TGACCCCTTT 300

TTAGAAGACG ATGCGATTAA AAGCATTGAT GAAGCCAAGC GGTTATTCAA AACATTAAAC 360

CGCCCCAATG TGATGATTAA AGTCCCGGCG AGTGAAAGCG CTTTTGAAGT CATTAGCGCT ’420

CTGGCTCAAG CCTCTATCCC CATTAATGTA ACTTTAGTCT TTTCGCCTAA AATTGCCGGT 480

GAAATCGCTC AAATCTTAGC CAAAGAAGCA CGAAAAAGAG. CGGTCATTAG CGTGTTTGTC 540

TCACGATTTG ACAAAGAAAT AGACCCACTA GTGCCACAAA ATTTGCAAGC TCAAAGTGGG 600

ATCATGAACG CTACCGAGTG TTATTATCAA ATCAACCAGC ATGCTAATAA GCTAATAAGC 660

ACCCTTTTTG CATCCACCGG CGTTAAATCT AATTCTTTAG CTAAAGATTA CTACATTAAA 720

GCGCTGTGTT TTAAAAACTC TATCAACACA GCCCCCCTAG ACGCCCTAAA CGCTTATTTG 780

CTTGACCCAA ACACCGAGTG TCAAACCCCT TTAAAAATCA CAGAAATTGA AGCGTTCAAA 840

AAAGAATTAA AAACGCACAA TATTGATTTA GAAAACACCG CCCAAAAACT CCTTAAAGAA 900

GGCTTGATAG CGTTCAAACA ATCCTTTGAA AAGCTTTTAA GCAGTTTTTG A 951 (2) Information for SEQ ID NO: 57:

(i) Sequence characteristics:

(A) Length: 783 base pairs (B) Type: nucleic acid (C) String: double (D) Topology: circular (ii) Molecule type: DNA (genomic) (iii) Hypothetical: NO (iv) Antisense: NO · · ·· ····

181 «vi vi vi vi vi vi vi vi vi vi vi vi vi vi vi (vi)

(A) Organism:

(ix) Features:

(A), 'Name / Key:

(B). Location: 1

Helicobacter pylori misc_character., 783 (x)

Sequence Description: SEQ ID NO: 57:

ATGAAAACAA

GTGGTGGCTT

AAATTGAATT

TTAAGGCCAG

AATCAAACCA

GTGGATAGCA

GTCGCTATGA

TCAGAACCCG

GCTGGGTTTG

ACGATGGATT

CATAGCGGAG

AAGAGCGCTT

CAAAGGAATT

TAA atggtcattt.

TATTAGTGGG

ACCATCCAGC

CTTTCCAATA

CGCTTAAAGT

GCGATAAAGA

ATGGCGAAAT

GGTTATTATT

TCAAGGTTAC

TGAGCGAGTT

GGTTAGTTAG

TGAATAAGAT

TAGAATCTTA

TAAGGATTTT. GCATGGAAAA GTGTAGCCCG CATATTATTG TAGCGAGAAA GTTCAAGCGT aatgcttttt aggcgcgagc AAACCAATGA

120

ISO

CAGCGATAAT

TGAAGAGATC

CGATTTTTCT

TGTTTTACGC

CTCCACTGGT

CATACTAGAG

GGACATCCAA

CACTATGGTT

TTTTGCAAGT

TCAAAAAGAC

ATTGCTAAAG ”AGTATGAAAA ~ CAAATTCAAG - 240

TTGCAAAATC AGGGCTATAA GGTTATTAAT 300

TTTGCGCAAA AAAAAGAAGG GTATTTGGCT 360

CCCGATCCTA AAAGGACCAT ACAGAAAAAA 420

TTGGATAAAA TGGAAAGGGT TTTAATCCCG 480

CCTATGAGTG GGGAATCTTT GGATTCTTTT 540

GAAAAATTCT TAAAAACCAC.CCATTCAAGC 600 AAGGGGACGG ATAATTCTAA TGACGCAATT 660

ATCATGCAAG AAATGGATAA GAAACTCACT 720

GCCAAGGAAT TAAAAAACAA GAGAAACCGA 780

(2) Information for SEQ ID NO: 58:

(i) Sequence characteristics :.

(A) Length: 4149 pairs (B) Type: nucleic acid (C) String: double (D) Topology: circular (ii) Molecule type: DNA (genomic) (iii) Hypothetical: NO (iv) Antisense: NO ( (vi) Original source:

(A) Organism: Helicobacter pylori (ix)

(A) Name / Key: misc_character (B) Location: 1 ... 4149 (xi) Description of Sequence: SEQ ID NO: 58:

TTGAATTTTA ATAACCTTAC GGCTAATGGG GCGTTAAATT TTAATGGTTA TGCGCCCTCT 60 TTAACTAAGG CTTTAATGAA TGTCAGCGGG CAGTTTGTTT TAGGGAATAA TGGGGATATT 120 AATTTATCTG ACATCAATAT CTTTGACAAC ATCACAAAAT CTGTAACTTA CAACATCTTA 180 AACGCTCAAA AAGGGATTAC TGGCATTAGT GGGGCTAATG GCTATGAAAA AATCCTTTTT 240 TATGGCATGA AAATCCAAAA CGCTACCTAT AGCGATAATA ACAACATCCA AACTTGGTCG 300TTTATAAACC CTCTCAATTC TTCTCAAATC ATTCAAGAGA GCATTAAAAA TGGGGATCTA 360 ACCATAGAAG TTTTAAATAA CCCTAACTCG GCTTCCAACA CTATTTTTAA TATCGCTCCT 420 GAGCTTTATA ATTACCAAGA . TTCTAAGCAA AATCCTACCG GCTATAGCTA TGATTATAGC 480 GACAÁTCAAG CAGGCACTTA TEACTTGACA 'AGCAACATTA AAGGTCTTTT CACCCCTAAA 540 GGCTCTCAAA CGCCTCAAAC CCCAGGCACT TATAGCCCAT TTAACCAGCC TTTGAATAGT S00 TTGAATATCT ACAATAAGGG TTTTTCTAGC GAGAATTTAA AAACGCTTTT AGGGATCCTT' ⁶⁵⁰ • · · · · ·· ···· · ··· • ····

1Q2 · A · A · A * * A A *

ATTGAATCCA ACCAACTAGA CAATATCACT AAGATTAAAA TCACCCAAGC GCAAAAGCAA GACAACATCA ATCAAACCTT TAATAACGGG GTTACAAACT CTACTAGCTC TATATGGTTT CTAGATAGCG CCACTTGTTC TTCTTTTAGA ACTTCCCCTT ATTTAGGCTA CATTAACGCT • GGGACAATTGGAAGTAGTAACGCTTTTGAA AGČGCTAATÁ · ACTTAGTGTT ί GAATAAAGCT TTTAATCTTT TGGGTCAAGA-AGGGATTGAT / GTTCTTAGTC, aaatggctat., Ggaaaaaatc GAAAACGCTC TAAGCCCTTT GAGTAAGGAA GGCCAACTTA TAGGTCAAAA, TAACTTAGAT>^'GAAATCCAAA: ACATTATCAG -TCAAAAACTA ; atcatagaaa actaccttgc taagcagtct 'TTGAATTTTA ITCGGTGGGTA TATAGACGCT TTAAAGGATA TTACTAACCC CCCTACAAGC GACTTGTTGA ACGAGTTTTT AGGACAAGAT GTGAGTAATA TCATCAATAA TGTTATTTCT GGTTTAGGGA GCGTGTTGCC GCCCTCTTTA ACTCTTTTAT CGCCTAGAGG CTTGCATGAT AGCAATGGCT ATGTTTTTGT CAATAACAGC AATTTTGTCG CCAACAAGTC .TATTATCTTT TATCAAGGCG CATTGATTTT TGCTTCTAAT AACGCCACTA ATGGCTTAAG CCTTAATGCG GAAATTTGTA TCAATTTAGC. CAATTGCCCT AGCGTAACCC CCACTAATGA GTCTTTAAGC ACAATCATCT CTAATGGGGC TATTGATTTG ACGCTCAATC TCAATGAAAA TGCGACCTTG TTTAACAACG CCTCTAACTC TACGGCTAAT GCGACTTTAA GCACTAACGC TAGTGGTTTG GATTTGGTGT TTAACCTCAG TCATTCAGTT GCGACGATCA TGGCCAATAA TAACCCTTTG GGTACTTACA CGCTGATTGA TAGCGCTAAA ACAGGAGGCA GTAGCCTGGA TAATTACCTT AAGCACATGG TGATGACTGA CAACGGCTTA GATGGCGGTT TAGTTGTAGG CTTTAAGGAC CTTTATAATA AAGTGAAAAT CGCTGTTTCT ACTTTAAAAC AATATATCGC TCAAATTCAG GCTGGGGGAA ATCAAGCGAT TAATTGGCTC TTATTCGCTC CCTATTATCT AGAGAGCCAC GATATTGCTA ACACTTTAGA AGTCATCGCT ATTTTACAGA TCAACACCTA CACGCAGCAA TCAACTTTCG CCCGTTCTGA TTTCTTAGAA GCTGATGCGA TCCCTAACGC TATGGATGTG AAAAATAATG TGTGGGCGAC AGGAGTTGGA ACTTTATATG GTATCAATGT AGGGTATGAT TATGCCGCTT ATGGGTATAG CGGGTTCCAT GTCAATGTGG GCGTTTATAG CCGAGCGTTT AATGAGACTT GGGGATACAA TAAAACTTTC ATCAATCAGT CTTACAGATA CGACACTTGG GATTTCATGT TTAAAGATAA AAGCGTTATT TACATTGGTT TGTCTGGTTT AAGGGGCATT GCCAATGCTG ACCCTAATAA AAAATCCGTT CATTATTTCA ATAAAAACTC TTATTATTTT ATTAATTCTA TGGGGGATAA AATGGTGCGT

TCTCAAAATT CCGCCACCTT AAAAGAAATG AACATTAATG AAGTGTTGCA ACTCTTAGAT GCGCTCCTAG AAACGATCAA CCATTTGACT AATCTCGTTA TAGGCGCTAC CCAAGATAAT GGGGGCAATG GCTATAGCAG CCCTTGCGCG AACACTTACT TGGGGCAATT ATTAGGCTCA 'GATTTTAAAG CTAAAAGCAT TTATATTACC AGCGGAGGGA GCGCGGATGT' AACCTTTCAA AACATAGAAG CTCAAGCCAC 'AGACAATATC AAAATCTTTA ATCAGGGGAA' .TTTAGCGAAT AAGCAAGCCG · GCGGTTTAGG. GAACTTTATA TTACCCGCTA GCTTGCAAGA TGAAACCTTA GATTTATTGA ATAATAGTGG, AGTCATGAAT -AGCATTTTTG GCAATTTTGT -TACCCCATCC TTAAAAAGCA TGCTAGACGATAAAGGGCTT TCTGAATTAA GCTCTAŤTTT AGGCGTGATT CTGCAAAAAG ACATTGGTGT GGTAGCGAAC GTTGTCAAAA AGCTAGAAAG TCAAGGCTTG CAAGGCGGGT TGAGCGGCGT TTATAATCAA CAAAACGCGC TCAAAGAAAA CGATTTAGGC TTTTGGCAAA AAGGGTATTT TAACTTTTTA TCTTTTAGTA ACGCTACTGG GGGTAGTTTG AATGGCGATA ATACGATTGA CTTTAGCAAG GGTGTTTCTA ATATCAATAT CACCACCCTA GGTTTGAATA ATGTGAGCGT TCAAAAAGGA ACAACCAAAA ACAGCTCTCC TGCAAACTCT GTGCACGCTA ATAATTTCAC TTTCTTAGGC TCTCAAGTAA CAAATAATAG CGTTATAGGC CAAGCTAATA ATTTAACGAT CACCAACGCT ATTGATGGTA ATTTCACCTT AAACCAACAA AATGTCATGG GGAATTTTAA TAGCTATGGC AGTCATGCTA TTATCAATAC TCAAGGCACA ATCCAATTCA ACGCTTCTTC AAAAGAAGTG GCCATTTATT ACGGGTATAA CAACCAAATC AAGCTTTATG CGCTCATTGA TATTAATGGC ACCTATAACG GGCAAGCCGT GAGCGTTAAA TCTCAAAATC AATACATTTA CACTTCCATT AATGATCCTA TCAATAACCC ACAAGCCCCC GGCGTTCAAA GCGTGGATAG CATCGATCAA AATAAAATCT TTGAAACTAA AGGAAGCCCT TCCACAAAAG ATTTAACCAC GATCGCT GGA AACCCTAATT TTAAAAATGA CGCCACTAAT ATGAGTCGTT TAGCCAAGCT CTCTGACACT CGCTTAGAAG CCCTTAAAAA CAAGCGATTC ΑΤΤΓΤΑΑΑΑΤ ACTCTCAAAG GAATAGAGTT GGGGCTAGTT TCATTAGTGG AGGTACŤGGA AGGTTTATTA AGGGCGTGAT TGTGGGAGGT GCAAACATCA CTCAATCAGG CTCTAGCAAT ATCAAAAGAA GCGAGCTAAC CATGAGCTTG ATCAACTCCT ATGACCCCCT ACTCTCAATC ACGACTGACG CTAAAATCAA TTATGGCTAT TTTAAACCCC AAGTAGGCTT AAGCTATTAT ATGGATGATC CTATTTACAA CCAATTCAGA CTAACGATCA ATTTTGCCCT AGAAAGTCGG GTGATTGCGG ATGTGGGCAG AGACTTATTC

720

780

840

900

960

1020 .1080

1140

1200

1260

1320

1380

1440

1500

1560

1620

1680

1740

1800

1860

1920's

1980

2040

2100

2150

2220

2280

2340

2400

2460

2520

2580

2640

2700

2760

2820

2880

2940

3000

3060

3120

3180

3240

3300

3360

3420

3480

3540

3600

3660

3720

3780

3840

3900

3960

183

· · • · • · · · • · · · • · · · • • · • · · • • • · • · • · · • · · · · • • · * • · • • • · · · · · · · ·· • ·· ♦ ·

TTCATCGGTA ATAACACCCT AAGCTATAGA GATGGTGGCA GATACAACAC TTTTGCTAGC 4020 ATTATCACAG GCGGGGAGAT AAGATTGTTC AAAACCTTTT GGCTTGATTA TAAAGATATT AATATTACCG GAAATATTGG TATGCGCTAT 4140 GCTTTTTAA · 4149 (2) Information for-SEQ ID NO: 59:

(i) Sequence characteristics:

(A) Length: 789 base pairs (B) Type: nucleic acid —String: double ------------ (D) Topology: circular (ii) Molecule type: DNA (genomic) (iii) Hypothetical: NO (iv) Antisense: NO (vi) Original Source:

(A) Organism: Helicobacter pylori (ix)

(A) Name / Key: misc_charakter (B) Location: 1 ... 789 (xi) Sequence Description: SEQ ID NO: 59:

ATGAAAAAAA TTGGTTTGAG CTTGTGTTTG GTTTTGAGTT TGGGTTTTTT AAAAGCCCAT 60

GAAGTGAGCG CTGAAGAGAT TGCGGATATT TTCTACAAAC TCAACGCCAA AGAGCCTAAA 120

ATGAAAATCA ACCACACGAA GGGGTTTTGC GCTAAAGGCG TGTTCCTCCC TAACCCGCAA 180

GCAAGAGAGG ATTTAGAGGT GCCACTACTC AATGAAAAAG AAATCCCTGC GTCTGTAAGG 240

TATTCTTTAG GGGGCGTGGC GATGGACGAT AAAAGCAAGG TTAGGGGAAT GGCGTTAAAA 300

CTAGAAAATC AAAACGCTAG TTGGACAATG GTGATGCTCA ATACAGAAAT CAATTTTGCC 360

AAAAACCCTG AAGAATTCGC CCAATTTTTT GAAATGAGAC TTCCTAAAAA TGGCAAGGTA 420

GATGAAGCAA GAATCAAAAA GCTTTACGAA GAAGTCCCCT CTTATAGGAA TTTTGCCGCC 480

TATATGAAAA CGATAGGGAT TAGCTCAAGC GTGGCTAATA CGCCTTATTA TAGCGTGCAT 540

GCGTTCAAGT TTAAAGATAA GAAAGAAAAA TTATTGCCTG CGAGGTGGAA ATTTGTGCCT 600

AAAGAGGGCG TTAAATACTT AAATCCTCAA GAATTAAAGC AAAAAGATTC AAATTATCTG S60

CTCTCTTCAT TCCAACAACA CCTTAAAAAT AAACCCATAG AATACCAAAT GTATTTGGTG 720

TTTGCGAATC AAAATGATGC CACCAACGAC ACGACCGCGC TTTGGAAAGG CAGCATAAGG 780

AATTATTAG 789 (2) Information for SEQ ID NO: 60:

(i) Sequence characteristics:

(A) Length: 741 bp (B) Type: nucleic acid (C) String: double • ·

184 (D) Topology: circular (ii) Molecule type: DNA (genomic) (iii) Hypothetical: NO (iv) Antisense: NO (vi) Original Source:

(A) OrganismusHelicobacter pylori (ix) Features: ___________ (A) Name / key: misc_charakter (B) Location: 1 ... 741 (xi) SEQUENCE DESCRIPTION: ATGAAACAAT TTAAAAAGAA ACCAAAAAAG ATCTTAAAGC GTCCTTTATG GCTTATGCCT TATGCGGATG GAACAGACAT TTTGGGGCTT GTGCATCGTC CATGGTATGC TATATGGAGT TTTACAGGAA ACCAACTCAT CACAAAAACT CACTCTCAAA ACAACCAAGA CATCACAGCC TTAAGCGGTC TGTATAACTA CACCGGAGGG TTAGGCAGTA ACGCTACTTT TAATCTAGGT TATCCTAATG GGCATACTGA TGTTACTTTT GTAGAAGTGG GCAATCGTGT GGGATCGGGA AACTTGAACG CTAATAAGGT TACTATCAAT GTGAATGTAG GCAATGCTAA CAGCGTTATT TACTTGCAGT TCTTTAGCTA G (2) Information for SEQ I

3EQ ID NO: 50:

ATAAAACGAT CGCATCAAAA TCAAAAAACA TTACTGATTG GCGGGTTTGC TAGTGGGGTG AGTTGGGGGG AAAAAAGCCA AAAGGTATGC TGCGATAAAT, GGGAGGAAAA AACACAACAA TGGGCC. TAACTACTAC AATTTAAAAA ATGATAACGG CACTTATTTT GAATATAATG GGGGGAATTT.AGACATTGAA GCGAGTAGTG GGAATAGCTT CACTTCTTGG AGCGCTGGGA CTATCAA

NO: 61:

120

180

240

300

360

420

480

540

600

660

720

741 (i) Sequence characteristics:

(A) Length: 738 pairs (B) Type: nucleic acid (C) String: double (D) Topology: circular (ii) Molecule type: DNA (genomic) (iii) Hypothetical: NO (iv) Antisense: NO ( (vi) Original source:

(A) Organism: Helicobacter pylori (ix)

(A) Name / Key: misc_charakter (B) Location: 1 ... 738

185

(xi) Sequence description: SEQ ID NO: 61:

. ATGATAAAAA AGACCCTTGC ATCGGTTTT TTAGGATTGA GTTTGATGAG - TGTGTTAAAT

GCCAAAGAAT GCGTTTCGCC CATAACAAGA AGCGTTAAGT ATCATCAGCA ► AAGTGCTGAG,: ATCAGAGCCT TGCAATTACA AAGTTACAAA ATGGCGAAAA TGGCGCTAGA CAATAACCTT. AAGCTCGTTA'AAGACAAAAA GCCAGCCGTC ATCTTGGATT TAGATGAAAC 'CGTTTTGAAC

ACTTTTGATT ATGCGGGCTA TTTAGTCAAA AACTGCATTA AATACACCCC · AGAAACTTGG

GATAAATTTG AAAAAGAAGG CTCTCTTACG CTCATTCCTG GAGCGCTAGA 'CTTTTTAGAA

AC GCATTCACTT TAAAAACGCT. CAAAAGCTTT AAGCTCCCCC AAGTGAGTGAIAGAATCCGTT

TTGTTAAAGG AAAAAGGCAA GCCTAAAGCC GTTAGGCGGG AGTTAGTCGC TAAGGATTAT _GCGATTGTTT TACAAGTGGG CGACACTTTG CATGATTTTG ACGCCATTTT TGCTAAAGAC

GCTAAAAACA GCCAAGAACA ACAAGCCAAA GTCTTGCAAA ACGCTCAAAA ATTCGGCACA

GAATGGATCA TTTTACCCAA CTCTCTTTAT GGCACATGGG AAGATGGGCC TATAAAAGCA

TGGCAAAATA AAAAATAA

SO .120

180

240

300

3S0

420

480

540

600

650

720

(2) Information for SEQ ID NO: 62:

(i) Sequence characteristics:

(A) Length: 867 base pairs (B) Type: nucleic acid (C) String: double (D) Topology: circular (ii) Molecule type: DNA (genomic) (iii) Hypothetical: NO (iv) Antisense: NO ( (vi) Original source:

(A) Organism: Helicobacter pylori (ix)

(A) Name / Key: misc_charakter (B) Location: 1 ... 867 (xi) Description of Sequence: SEQ ID NO: 62:

TTGTGGTGTT TAAAAACCCC TATCATAGGG CATGGCATGA AGAAAAAAGC AAAAGTCTTT TGGTGTTGTT TTAAAATGAT TCGTTGGTTG TATTTGGCGG TCTTTTTTTT GTTGAGCGTA TCAGACGCTA AAGAAATCGC TATGCAACGA TTTGACAAAC AAAACCATAA GATTTTTGAA ATCCTTGCGG ATAAAGTGAG CGCCAAAGAC AATGTGATAA CCGCCTCAGG GAATGCGATC CTATTGAATT ATGACGTGTA TATTCTAGCG GATAAGGTGC GTTATGACAC CAAGACTAAA GAAGCGTTAT TAGAAGGCAA TATTAAGGTT TATAGGGGCG AGGGCTTGCT CGTTAAAACC GATTATGTGA AATTGAGTTT GAACGAAAAA TATGAGATCA TTTTCCCCTT TTATGTCCAA GACAGCGTGA GCGGGATTTG GGTGAGCGCG GATATTGCTA GCGGGAAGGA TCAAAAATAT AAGATTAAAA ACATGAGCGC TTCAGGGTGC AGCATTGACA ACCCCATTTG GCATGTCAAT GCGACTTCAG GCTCATTTAA CATGCAAAAA TCGCATTTGT CAATGTGGAA TCCTAAGATT TATGTCGGCG ATATTCCTGT ATTGTATTTG CCCTATATTT TCATGTCCAC GAGCAATAAA AGAACTACCG GGTTTTTATA CCCTGAGTTT GGCACTTCCA ACTTAGACGG CTTTATTTAT TTGCAACCCT TTTATTTAGC CCCCAAAAAC TCATGGGATA TGACCTTTAC CCCACAAATC CGTTACAAAA GGGGTTTTGG CTTGAATTTT GAAGCGCGCT ACATCAACTC TAAGACGCAG GTTTTTATTC AATGCGCGCT ATTTTAG

120

180

240

300

360

420

480

540

600

660 ‘720

780

840

867 • * 9

186 (2) Information for SEQ ID NO: 63:

(i) Sequence characteristics:

(A) Length: 387 base pairs (B) Type: nucleic acid _J (C) String: double ~ (D) Topology: circular (ii) Molecule type: DNA (genomic) (iii) Hypothetical: NO (iv) Antisense: NO (vi) Original source:

(A) Organism: Helicobacter pylori (ix) Properties: (A) Name / Key: misc_character (B) Location: 1 ... 387 (xi) Sequence Description: SEQ ID NO: 63:

TTGATGTTTA AAAAAATGTG TTTGAGCCTG CTAATGATAA GCGGTGTTTG TGTGGGGGCA AAGGATTTGG ATTTCAAGCT GGATTATCGC GCGACTGGGG GGAAATTCAT GGGGAAAATG ACGGACTCTA GTCTTTTAAG TATCACTTCT ATGAACGATG AACCGGTGGT GATTAAAAAC CTTATTGTCA ATAGGGGAAA TTCATGCGAA GCGACTAAAA AAGTAGAACC CAAATTTGGC GATAAGTTTA AAAAAGAAAA ACTCTTTGAT CATGAATTAA AATACTCGCA ACAGATATTT TACCGCCTGG ATTGCAAGCC TAACCAATTG TTAGAAGTTA AAATCATCAC GGACAAGGGC GAATATTACC ATAAATTTTC CAAATAG (2) Information for SEQ ID NO: 64:

(i) Sequence characteristics:

(A) Length: 510 bp (B) Type: nucleic acid (C) String: double (D) Topology: circular (ii) Molecule type: DNA (genomic) (iii) Hypothetical: NO

120

180

240

300

360

387 ·· · ·

187 (iv) Antisense: NO (vi) Original Source:

(A) Organism: Helicobacter. pylori (ix) Features:

- · ,. (A) Name / Key: misc_character (B) Location: 1 ... 510 '.

(xi) Sequence description: SEQ ID NO: 64:>

; . i

ATGCAAGCGT TAAAATCATT GCTTGAAGG ATTACAAAAC TCCAGAATCT AGGCGGCTAT 60

TTGATGCATA 'TAGCTATTTT-CATCATTTTT' ATTTGGATTG GAGGGCTTAA GTTTGTGCCT__120

TACGAAGCTG AAGGGATCGC CCCTTTTGTG GCCAACTCCC CTTTCTTTTC TTTCATGTAT ~ X8O 'AAATTTGAAA AACCTGCATA CAAACAACAC AAAATGTCTG AATCCCAATC CATGCAAGAA 240 GAAATGCAAG ATAACCCTAA AATCGTTGAA AACAAAGAAT GGCATAAAGA' AAACCGCACT 300 TATTTAGTGG CTGAAGGTTT AGGGATTACG ATCATGATCC TAGGCATTTT GGTGCTTTTG 360 GGGCTTTGGA TGCCTTTAAT GGGCGTAGTT GGGGGCTTGC TTGTCGCTGG AATGACGATC 420 ACCACCCTAT TCTTTTTTAT TCACAACGCC AGAAGTGTTT GTCAATCAGC ATTTCCCATC 480 GCTTTCTGGG GCTGGAAGGC TAGTGGTTAA, 510 (2) Information for SEQ ID NO: 65:

(i) Sequence characteristics: '(A) Length: 1464 bp / 7 (B) Type: nucleic acid 7 J (C) String: double. (D) Topology: circular (ii) Molecule type: DNA (genomic) (iii) Hypothetical: NO (iv) Antisense: NO (vi) Original Source:

(A) Organism: Helicobacter pylori (ix)

(A) Name / Key: misc_charakter (B) Location: 1 ... 1464 (xi) Description of Sequence: SEQ ID NO: 65:

ATGATTGAAT GGATGCAAAA TCATAGAAAG TATTTAGTGG TTACGATATG GATAAGCACG 60 ATCGCTTTTA TTGCCGCCGG AATGATAGGT TGGGGGCAAT ACAGCTTTTC TTTAGATAGC 120 GATAGCGCTG CCAAAGTGGG ACAGATTAAG ATTTCTCAAG AAGAATTAGC CCAAGAATAC 180 CGCCGCCTTA AAGACGCCTA ŤGCTGAGTČT ATCCCTGATT TTAAAGAACT CACCGAAGAT 240 CAAATCAAAG CCATGCATTT AGAAAAAAGC. GCGCTAGATT CGCTCATCAA TCAAGCTTTA 300

and.

188 • ·

TTGAGGAATT TCGCTTTAGA TTTAGGGCTT GGTGCTACCA AGCAAGAAGT GGCCAAAGAG 360

ATCAGAAAAA CGAACGTTTT TCAAAAAGAT GGCGTTTTTG ATGAAGAATT GTATAAAAAT 420

ATCTTAAAAC AAAGCCATTA CCGCCCCAAG CATTTTGAAG AAAGCGTTGA AAGGCTTTTA 480

ATCCTTCAAA AAATCAGCGC TCTATTCCCC AAAACCACCA CCCCTTTGGA GCAATCCAGT 54 0

CTATCGCTTT. GGGCAAAATT GCAAGACAAA TTAGACATTC TTATCCTAAA TCCTAATGAT '600

GTTAAAATCT CTCTCAATGA AGAAGAGATG AAAAAATATT ATGAAAACCA TAGAAAGGAT 660

TTTAAAAAGC CCACAAGCTT TAAAACACGC TCTTTATATT TTGACGCTAG TTTAGAAAAA .720

ACTGATTTGA AAGAGTTGGA GGAATACTAC CATAAAAACA'AGGTGTCTTA 'TTTGGACAAA 780

GAGGGGAAA‘TACAGGATTT TAAAAGCGTT-CAAGAGCAAG.TCAAGCATGA TTTAAACATG 840.

CAAAAGGCGA, ATGAAAAAGC CTTAAGGAGC TATATCGCTC .TAAAAAAGGG GAACGCACAA 900 .

AACTACACCA CGCAAGATTT TGAAAAAAAC AACTCCCCCT ATACTGCTGA AATCACGCAA 960 ..

AAACTCACCG. CTCTCAAGCC CGTTGAAGTC CTAAAACCAG AGCCTTTTAAAGATGGTTTT, 1020 ATCGTGGTGC AGCTTGTCTC 'TCAAATTAAA GACGAATTGC AAAATTTTCA TGAAGCCAAA 1080 AGCGCTCTT AACACCGGTCT GACT

AAAGAAAAGC .. TTAAGGATTT TAAAGGGAAA'AGCGTGGGTT ATGTAAGCCC TAATTTTGGA 1200,

GGCACTATA 'GTGAACTTAA CCAAGAAGAG AGCGCGAAGT TTAATACAC CCTTTTTAAC, 1260 CGCCAGGAAA AAAAAGGGTT TGTAACCATA · GGTAATAAAG TGGTGCTTTA TCAAATCACA 1320 CTTTAGGG GAAGAAAACC AATACATGCA GCGTTTAGTC 1380

AATAACACTA AAACGGATTT TTTTGATAAA GCGTTGATAG AAGAATTGAA AAAACGCTAT — 1440 ----------- AAGATAGTCA AATACATTCA ATAA. . · ¹⁴⁶⁴ (2) Information for SEQ ID NO: 66:

(i) Sequence characteristics:

(A) Length: 429 base pairs ( ^β ) Type: nucleic acid '(C) String: double .-. ;

(D) Topology: circular.

(ii) Molecule type: DNA (genomic) (iii) Hypothetical: NO (iv) Antisense: NO (vi) Original source:

(A) Organism: Helicobacter pylori (ix)

(A) Name / Key: misc_charakter (B) Location: 1 ... 429 (xi) Sequence Description: SEQ ID NO: 66:

ATGAAAACGA ACTTTTATAA AATTAAATTA CTATTTGCTT GGTGTCTTAT CATTGGCATG 60 TTTAACGCTC CGCTTAACGC TGACCAAAAC ACGGATATAA AAGATATTAG TCCTGAAGAT 120 ATGGCGCTAA ATAGCGTGGG GCTTGTTTCT AGAGATCAGC TAAAAATAGA GATCCCTAAA 180 GAAACCCTAG AGCAAAAAGT GGCCATACTC AATGACTATA ATGATAAGAA TGTTAATATC 240 AAGTTTGACG ACATAAGTTT AGGGAGTTTC CAACCTAATG ATAATCTAGG TATCAATGCG 300 ATGTGGGGCA TTCAAAATCT TCTCATGAGC CAAATGATGA GCAATTACGG TCCAAACAAT 360 TCTTTCATGT ATGGCTATGC GCCAAČATAC TCAGATTCAT CGTTTTTACC ACCGATCTTA 420 GGGTATTAA (2) Information for SEQ ID NO: 67:

(and). .Characteristics of sequence:

_f ·, (A) Length: 627 (pairs of baffles (B) Type:. · nucleic acid '- (O String: -double (D) Topology: circular / ((ii) Molecule type: DNA' (genomic)

(Iii) Hypothetical: NO '. q

(iv) Anti-sense -: - NO -------------—--- γ ----- (vi) Original Source: í;

(A) Organism: Helicobacter pylori

J. (ix) Features: -y (A) Name / Key: misc_character of (B) Location: 1 ... 627 (xi) Sequence Description: SHEQ ID NO: 67:

TTGATCAACA ATAATAATAA CAATAAAAAA CTGAGAGGCT TTTTTTTGAA * AGTTCTCTTA, 60 AGTCTCGTTG. TTTTCAGTTC GTATGGGTCA GCAAATGACG ATAAAGAAGC CAAAAAAGAA GCGCTAGAAA 120 AAGAAAAAAA CACTCCCAAT GGGCTTGTTT ATACGAATTT 'AGATTTTGAT 1:80 AGTTTTAAAG CGACTATCAA AAATTTGAAA GACAAGAAAG TAACTTTCAA AGAAGTCAAT 240 CCCGATATTA TCAAAGATGA AGTTTTTGAC TTCGTGATTG TCAATAGAGT CCTTAAAAAA 3.00 ATAAAGGATT TGAAGCATTA CGATCCAGTT ATTGAAAAAA TCTTTGATGA AAAGGGTAAA 360 GAAATGGGAT TGAATGTAGA ATTACAGATC AATCCTGAAG TGAAAGACTT TTTTACTTTC 420 AAAAGCATCA GCACGACCAA CAAACAACGC TGCTTTCTAT CATTGCACGG AGAAACAAGA 480 GAAATTTTAT GCGATGATAA GCTATATAAT GTTTTATTGG CCGTATTCAA TTCTTATGAT 540 CCTAATGATC TTTTGAAACA CATTAGCACC ATAGAGTTCC

(i) Sequence characteristics:

(A) Length: 738 base pairs (B) Type: nucleic acid (C) String: double (D) Topology: circular (ii) Molecule type: DNA (genomic) i

(iii) Hypothetical: NO ' (iv) Antisense: (vi) Original Source:

NO

190 • 0 0000 (A)

(ix) Features:

(A) Name / Key:

(B) Location: 1

Helicobacter pylori mi with c_charakt er. .738 (xi) Sequence Description: SEQ, ID NO: 68:

ATGGCAGGCA '

TCAATCATCT

ÁTGACAGCAG

ATGACCCAAT

CAACAATACA

ATCTTAAATÁ

CAAATTAGTG

AATCCTAGCG

ACGGTTGAAA

CTAGCTCTAC

GATTCCCTTG

AGTTGCATGC

ACCAGCGGTT

CACAAGCTAT ATATGAATCA'TCTTCTGCAG GATTCTTATC GCAAGTCTCC CAAGCACAAG. TGGTGTCGCA GGGCCATTTG CAGGAATAGT AGCGGGCGCT · CGATTATTCC TATTGTTGTG. GGATTTACTA ·· ATCCGCAAAT GACCGCTATC ACAATCAAAG CATCGCTGAA GCTGTAAGCG TGCCTATGAA AGCCGCTAAC ACCAATTGTA TCAAGGTTTT AACGATCAAA GCATGGCTGT GGGGAACAAT

TCAGCAAATT AACAGGGGAA TTTAACGCGC AAGGCAACAC GCAAAGCGCG CTGTCAATAG TCAGATTGCA AGCATTTTAG CGAGTAACAC TACCCCTAAA CTATTGAAGC TTATGCGACG AATCAAATCG CTGTTCCTAG CGTGCCAACA TGATGAGCGG TATATTAGGC AATATTACAA GCGCAGCACC AAAATACGCC AAGAGCAACT GCGTTCTCAA GCAAGCAACA GCTCAATGAA -TGATACAGCC ATAGCTGTAC CGCTTTAGGC GCACTTGTTG GCTCATCAAA-ÁGTGTTTTTC AAATTTCTAT GACTCCTATG AGTGTTTCTA TGCCCACTGT TATGCCAAAT GCCACTAA 120 and

180

240

300

360

420

480

540

600

660

720

(2) Information for SEQ ID NO: 69:

(i) Sequence characteristics:

(A) Length: 1104 base pairs (B) Type: nucleic acid (C) String: double (D) Topology: circular (ii) Molecule type: DNA (genomic) (iii) Hypothetical: NO (iv) Antisense: NO ( (vi) Original source:

(A) Organism: Helicobacter pylori (ix)

(A) Name / Key: misc_charakter (B) Location: 1 ... 1104 (xi) Description of Sequence: SEQ ID NO: 69:

9999

191

ATGATTAAAA GCGTAGAGAT TGAAAATTAC TTTAAACTCA TCAACTTTTT TACCGGTCAA GCTCTTTATA CCAACACAGG CCTTTGTGAT GAACATGCCG TGAATATTAG TGAATTCAGA TATGACAAAC. .CTCCAATTTT 'CCTACAATCC ATCCCTTTCC 7 CAAAACCTAG' GTTTAATCCA.-TTCTAATTTA • 3 GCGATGTTTA -TTCCTATAGA ATTATCTATT

- CAATTAGCAA 'GCAAAGAAAA AGAATTGATT' TTAAATGCTA ATACAA7AAG 'AAAGTCTGTC

- ', CTAGAAGAAA .GTCCCAAAAG? GCTTTTAAAT 'attátggtga GCATTCTTAT. AGACAATCGT / AGCGGTTTGC ACCATACAAA AATGCHAAGAG • 'AAATTACAGA ^: TTCAAATTTT ^! TGCCACCACG '' AACACGATAT CCGATAATGA AAGGGGAGTT

AAAGAAAGCG cttctggctt TATCAGACAC AGGGGTATGG AGGTTAGAGG CTGA

AAAAATTTTG AGCACCTTAA AATGGAAAAT AACGATGCGG GTAAAACCAA TCTTTTAGAA CCTACTGCCA ATCAAGTCAG TCTTCCTCCT 'AAAATCAAAC TCGATGCCGA CAACOTAAAA CCCATTAGTA TCCGCACTGA' ATTTGAACAT ACACAAACCA 'GTTACAGCAA AGACATCAAT CTTATAAACA ¹ CAACÁATAAC GAAGCCACAG CCCATG ACAA' TGACTTATGÁ 'ATTTGAAAGG GATAAAATCG' CTCAAACCTA. TAAAGAAAAT GTTAATTCTC TTAAAGCATT-GGAAAATTTA GAAATCCTAC '>. AATGTTTCAA .CCCTAATATT TATA7CCAAA TCAAAGATGAAAACACACCG TTGTTTGGTT · GGGGTTTTAT CAAATTCTTT GTCAAGTATC TTTTTATTGA TGAAATAGAA TTTTTTAAAAG AAACGCCATC TTTAAAGACA TAGCCTTGTT TGAGCTTGAA AGCTATTCTA TGCTAGAAAA AGCGCTTTAT

120 180 240 300 360 420 480 -540 '600 .660' 720 '• .780 .840 900 960 1020 1080

-1104— (2) Information for SEQ ID NO: 70:

(i) Sequence characteristics:

(A) Length: 1230 bp (B) Type: nucleic acid (C) String: double '(D) Topology: circular (ii.) Molecule type: DNA (genomic) * \ * ·' (iii) Hypothetical: NO Iv (iv) Antisense: NO (vi) Original Source:

(A) Organism: Helicobacter pylori (ix)

(A) Name / Key: misc_charakter (B) Location: 1 ... 1230 (xi) Description of Sequence: SEQ ID NO: 70:

ATGTCCTTGA TTAGAGTGAA TGGGGAAGCT TTTAAACTCT CTTTGGAAAG TTTAGAAGAA 61

GATCCTTTTG AAACTAAAGA AACGCTAGAA ACGCTAGAAA CGCTTATCAA ACAAACGAGC 120 GTTGTTTTAT TGGCCGCTGG GGAGTCTAAG CGTTTTTCTC GTGCGATTAA AAAGCAGTGG 180 CTACGCTCTC ACCACACCCC CTTATGGCTC AGCGTGTATG AAAGCTTTAA AGAAGCCCTA 240 GACTTTAAGG AAGTCATTCT AGTTGTAAGC GAATTGGATT ATGTTTATAT CCAACGCCAT 300 TACCCCAAAA TCAAGCTTGT AAAAGGCGGG GCATCAAGGC AAGAATCCGT GCGTAACGCT 360 TTGAAAGTAA TTGATAGCAC TTACACGATC ACCAGCGATG TGGCTAGGGG TTTAGCGAAT 420 ATGGAAGCGC TTAAAAGCTT GTTTTTAAČC CTCCAACAAA CGAGCCATTA TTGCATCGCC 480 CCTTACTTGC CTTGCTATGA CACAGCGATC, TATTATAACG AGGCTTTAGA TAGAGAAGCG 540 ATCAAACTCA TTCAAACCCC GCAATTAAGC CACACCAAAA CGCTCCAATC AGCCCTAAAC 600 CAAGGGGGTT TTAAAGATGA AAGCAGCGCG; ATTTTACAAG CTTTCCCTAA CTCTGTGAGC 660

192 • · ···

TATATTGAAG GCAGTAAGGA TTTGCACAAA CTCACCACAA GCGGCGATTT AAAGTTTTTT, 720 ACGCCTTTTT TTAACCCAGC AAAGGACACT TTTATAGGCA TGGGTTTGTGTGTGTGTGTGTGTGT 840 AAGGCTCATA GCGATGGCGA TGCTTTATTG CATGCGGTTA TTGATGCGAT TTTAGGAGCG 900 ATTAAAGGGG GGGATATTGG CGAATGGTTC CCTGATAATG ACCCCAAATA CAAAAACGCC 960 TCTTCTAAAG'AGCTTTTAAA'AATCGTGTTG'GATTTTTCTC AAAGCATTGG''GTTTGAATTG of 1020 CTTGAAATGG -GAGCGACCAT CTTTAGCGAA 'ATCCCTAAAA TCACTCCTTA CAAACCGGCG 108 0' ATTTTAGAGÁ-) ÁTTIGAGCCA-'ACTrTTGGGT / 'TTAGAAAAAT; CTCAAATCAGI ^, .CTTGAAAGCC 1140 ACTACAATGG 'AAAAAATGGG-GTTCATTGGC AAACAAGAAG GGCTGTTAGT CCAAGCGCAT 1200 GAGAGCATGC GTTATAAACA AAAACTTTAA · 1230 (2) Information for SEQ ID NO: 71:

“Ti”) Sequence characteristics ^- : - --- (A) Length: 813 pairs of bass (B) Type: nucleic acid (C) String: double (D) Topology: circular (ii) Molecule type: DNA (genomic) (iii) Hypothetical: NO (iv) Antisense: NO (vi) Original Source: / (A) Organism: Helicobacter pylori (ix) Properties:

(A) Name / Key: misc_charakter (B) Location: 1 ... 813 (xi) Sequence Description: SEQ ID NO: 71:

ATGAAAAAGT TTGTAGCTTT AGGGCTTCTA TCCGCGGTTT TAAGCTCTTC GTTGTTAGCC 60 GAAGGTGATG GTGTTTATAT AGGGACŤAAT TATCAGCTTG GACAAGCCCG TTTGAATAGC 120 AATATTTATA ATACAGGGGA TTGCACAGGG AGTGTTGTAG GTTGCCCCCC AGGTCTTACC 180 GCTAATAAGC ATAATCCAGG AGGCACCAAT ATCAATTGGC ACTCCAAATA CGCTAATGGG 240 GCTTTGAATG GTTTTGGGTT GAATGTGGGT TATAAGAAAT TCTTCCAATT CAAGTCGCTA 300 GATATGACAA GCAAGTGGTT TGGTTTTAGA GTGTATGGGC TTTTTGATTA CGGGCATGCC 360 GATTTAGGTA AACAAGTTTA TGCACCTAAT AAAATCCAGT TGGATATGGT CTCTTGGGGT 420 GTGGGGAGCG ATTTGTTAGC TGATATTATT GATAAAGACA ACGCTTCTTT TGGTATTTTT 480 GGTGGGGTCG CTATCGGCGG TAACACTTGG AAAAGCTCTG CAGCAAACTA TTGGAAAGAG 540 CAAATCATTG AAGCCAAAGG TCCTGATGTT TGTACCCCTA CTTATTGTAA CCCTAATGCC 600 CCTTATAGCA CCAACACTTC AACCGTCGCT TTTCAAGTGT GGTTGAATTT TGGGGTGAGA 660 GCCAATATCT ACAAGCATAA TGGCGTGGAA TTTGGCGTGA GAGTGCCGCT ACTCATCAAT 720 AAATTTTTGA GCGCGGGTCC TAACGCTACT AACCTTTATT ACCATTTGAA ACGGGATTAT 780 TCGCTTTATT TGGGGTATAA CTACACTTTT TAA ⁸¹³ (2) Information for SEQ ID NO: 72:

\> » ^; • '/' ·? * *. ' 1 '

ΒΒ ····

193 '

(i) Sequence characteristics:

(A) Length: 1317 pairs (b) Type: · nucleic acid (C) String: double (D) Topology: circular (ii) Molecule type: DNA (genomic) (iii) Hypothetical: NO (iv) Antisense: NO ___ (vi) _Original_Source _: _______________________ (A) Organism: Helicobacter pylori (ix) Features:

(A) Name / Key: misc_charakter (B) Location: 1 ... 1317 (xi) Description of Sequence: SEO ID NO: 72:

ATGGCTTACA AACCTAACAA AAAGAAGTTA AAAGAATTAA GAGAGCAACC GAATTTATTT AGCATCTTAG ATAAGGGCGA TGTTGCAACA AACAATCCTG TTGAAGAGTC AGACAAGGCC AATAAAATAC AAGAGCCACT CCCTTATGTC GTGAAAACGC AAATCAATAA AGCAAGCATG ATTTCTAGAG ATCCTATTGA ATGGGCAAAG TATTTAAGCT TTGAAAAACG AGTCTATAAG GATAATAGTA AAGAAGATGT CAATTTCTTT GCCAATGGTG AGATAAAAGA AAGTTCTCGT GTTTATGAAG CGAATAAAGA AGGGTTTGAA AGGCGCATCA CTAAAAGATA CGATCTGATT GATAGAAATA TTGATAGAAA TAGAGAATTT TTTATAAAAG AAATTGAAAT TCTAACCCAC ACAAACAGCT TAAAAGAATT GAAAGAGCAA GGGTTAGAAA TCCAATTGAC CCACCATAAT GAAACGCATA AGAAAGCCTT AGAAAATGGC AATGAAATCG TTAAAGAATA CGACCATCTT AAAGATATTT ACCAAGAAGT AGAAAGAACA AAAGATGGTG GATTGGTAAG AGAAATAATC CCCAGTATTT CTAGCGCTGA GTATTTCAAG CTTTACAACA AACTGCCTTT TGAATCAATA AACAATGAAA ATACCAAACT GAATACTAAC GACAATGAAG AAGTTAAAAA ACTAGAATTT GAATTAGCTA AAGAAGTGCA TATTTTAATC CTAGAGCAAC AATTGCTTTC AGCAACAAAT TATTATTCTT GGATAGATAA AGATGATAAT GCGAATTTTG CTTGGAAAAT GCATAGGCTT atcaatgaaa ataaactcaa agaaaaccat ctcagcgcca ataacgctaa taagattaag CAATTTTTCT TTAATAATGG TTCTATTTTA GGCTGGACTA AAGAAGAACA AAGCGCTATA CAAGAAAACA GAGATTATTC TTTAAGAAGC GCTCTTTTAA GTTTAGAAGA AATCGCTCAA GCAAAAATTG AATTGCAAAA ATACTATGAA AGCGTTTATG TTAATGGTGA TGGGAATAAA AGAGAAATCA AGCCTTTTAA AGAAATTTTA AGAGACACCA ACAATTTTGA AAAAGCTTAT AAGGAGCGTT ATGACAAATT GGTAAGCTTG AGTGCAGCAA TCATTCAAGC TAAAGAGGGT GGTAATGAGC GACCAAATTC TAGTGCAAAT AACAATAACC CTATTAAAAA TACAATAGAG ACTAATACTT CTAACAATAT TATTCAAAAT AATGATAATA TAATCATCCA AATTTAA (2) Information for SEQ ID NO: . 73:

(i) Sequence characteristics:

(A) Length: 648 base pairs (B) Type: nucleic acid (C) String: double (D) Topology: circular

120

180

240

300

360

420

480

540

600

560

720

780

840

900

960

1020

1080

1140

1200

1260

1317

194 (ii) · Molecule type: DNA (genomic). , (iii) Hypothetical: NO (iv), Antisense: NO (vi) Original Source:. ..

(A) Organism: Helicobacter pylori (ix)

(A) Name / Key: misc_charakter

-, - (- B -) - Local -: - 1.-.-; 648 ---- (xi) Description of sequence: SEQ ID NO: 73:

ATGCAAGCGT TAAAATCATT GCTTGAAGTG ATTACAAAAC TCCAGAATCT ’AGGCGGCTAT TTGATGCATA TAGCTATTTT ATCTTGGATTG GAGGGCTTAA GTTTGTGCCT

TACGAAGCTG AAGGGATCGC CCCTTTTGTG AAATTTGAAA AACCTGCATA CAAACAACAC GAAATGCAAG ATAACCCTAA AATCGTTGAA TATTTAGTGG CTGAAGGTTT ÁGGGATTACG-ATCATGATCC TAGGCATTTT GGTGCTTTTG GGGCTTTGGA TGCCTTTAAT GGGCGTAGTT / GGGGGCTTGC TTGTCGCTGG AATGACGATC ACCACCCTAT CTTTTTTATT CACAACGCCA GAAGTGTTTG TCAATCAGCA TTTCCCATGG CTTTCTGGGG CTGGAAGGCT AGTGGTTAAA 'GACTTGGCGT' TATTTGCTGG AGGCTTGTTT GTGGCCGGAT TTGATGCGAA ACGCTATTTG GAGGGTAAAG GGTTTTGCTT GATGGACCGC TCATCGGTAG GGATTAAAAC TAAATGCTCT AGCGGGTGTT, GCTCTTAA ( 2) Information for SEQ ID NO: 74:

(i) Sequence characteristics:

(A) Length: 186 amino acids (B) Type: amino acid (D) Topology: linear (ii) Molecule type: protein (iii) Hypothetical: YES (vi) Original source:

(A) Organism: Helicobacter pylori (ix)

(A) Name / Key: misc_charakter (B) Location: 1 ... 186 (xi) Sequence Description: SEQ ID NO: 74:

Met Ile Lys Arg Ile Ala Cys Ile Leu Ser Leu Ser Ala Ser Leu Ala ^{1 5} '2nd 15 °

Leu Ala Gly Glu Val Gn Gly Phe Met Gly Ala Gly Tyr Gin Gin i 20, 25 30

Gly Arg Tyr Gly For Tyr Asn 'Ser Asa Tyr Ser Asp Trp Arg w-La Gly

S0

120

180

240

300

360

420

480

540

600

648

I ’

195 ·· ·· ···· • '. · · · ·

9999 ·· 9

.. 9 9 ·· ♦ · · · · · · · · · ·

9 · 99 \

35 40 45 Asn. Asp Leu Tyr Gly Leu Asn Phe Lys Leu Gly Phe Val Gly 50 55 60. Asn Lys Trp Phe Gly Ala Arg Wall Tyr Gly Phe Leu Asp Trp Phe Asn .65 70 75 80 • Thr- : Ser'Gly .Thr Glu His 'Thr: Lys Thr Asn Leu 'Leu' Thr TyrGly Gly 85 90 95 Gly. Glý / AAsp Leu Ilé, Wall: Asn Leu. Ile- For Leu Asp. Lys JPhe. Ala .'Leu 100 ALIGN! 105 ‘110 'Gly Leu.Ile Gly Gly 'Wall Gin Leu Ala Gly Asn Thr · '.Trp Met Phe. For .. 115 . * 120 .125 Tyr Asp Val ' Asn Gin Thr Arg Phe Gin Phe Leu Trp · ‘Asn :. Leu. 'Gly. Gly 130 ' 135 > 140 Arg Met Arg Wall Gly Asp Arg Ser Ala Phe Glu Gly Val. Lys. Phe 145 150 155 160 For Meť Val Asn ' Gin , Gly Ser Lys Asp Wall Gly Leu Ile Arg Tyr Tyr 165 170 175 Ser Trp Tyr Wall Asp Tyr Val Phe Thr Phe

180 185 (2) Information for SEQ ID NO: 75:

(i) Sequence characteristics:

(A) Length: * 116 amino acids (B) Type: amino acid (D) Topology: linear (ii) Molecule type: protein (iii) Hypothetical: YES (vi) Original source:

(A) Organism: Helicobacter pylori (ix)

(A) Name / Key: misc_charakter (B) Location: 1 ... 116

(xi) Sequence description: SEQ. ID NO: 75: Leu Met Arg Ile Ile Ile Arg Leu Leu Ser Phe Lys Met Asn Ala Phe 1 ' 5 10 1S Leu Lys Leu Ala Leu Ala Ser Leu Met Gly Gly Leu Trp Tyr Ala Phe 20 May 25 30 Asn Gly Glu Gly Ser Glu Ile Wall Ala Ile Gly Ile Phe Wall Leu Ile 35 40 45 Leu Phe Wall Phe Phe Ile Arg For Wall Ser Phe Gin Asp For Glu Lys 50 55 60 Arg Glu Glu Tyr Ile Glu Arg Leu Lys Lys Asn His Glu Arg Lys Met 65 70 75 80 Ile Leu Gin Asp Lys Gin Lys Glu Glu Gin Met Arg Leu Tyr Gin Ala 85 90 95 Lys Lys Glu Arg Glu Ser Arg Gin Lys Gin Asp Leu Lys Glu Gin Met 100 ALIGN! 105 110

Lys Lys Tyr Ser. _; ** ·· ····

196.

• · · ·

(2) Information for SEQ ID NO: 76:

(.i) 'Sequence characteristics:

(A) Length: 345 amino acids (B) Type: amino acid

--- (D -) - Tdpol-og-ie -: -— 1-i-neural ------------- (ii) Type, molecules: protein (iii) Hypothetical: YES ( (vi) Original source:

(A) Organism: Helicobacter pylori (ix)

(A) Name / Key: misc_charakter (B) Location: 1 ...- 345

(xi) Description sequence: SEQ ID NO: 76: Met 1 Val Lys His Tyr Leu Phe Met 5 Ala Wall 10 Ser Gin Phe Phe Ser 15 Dec Phe Phe Leu 20 May Leu Phe Phe Ile Ser 25 Ser Ile Val Leu Ile Ser 30 XI e Ala Ser 35 Thr Leu Val Ile 40 Lys Wall Ser Phe Leu Gin Phu Leu 50 Tyr Ser Leu Pro 56 Gly Thr Ile Phe Ile Leu Pro 60 Ile 65 Thr Phe Ala Ala Cys Ala Leu Gly Leu Ser Arg Asp His Glu Leu Leu Val Phe Phe Ser Leu 90 Gly Val Ser Lys Lys 95 Met Thr Lys Ala Phe Val Leu Ser 105 Leu Leu Val Ser Ala Ile Leu Leu Ala Phe Ser 115 Leu Ile 120 For Thr Ser Lys Ser Ala Tyr Tyr ¹²⁸ Gly Phe Leu Arg 130 Gin Lys Lys Asp Lys Ile Asp Ile Asn Ile Arg Ala 140 Gly 145 Glu Phe Gly Gin Lys Leu Gly ISO Asp Trp Leu Val Tyr Val Lys 155 160 Thr Glu Asn Asn Ser Tyr, Asp Asn ¹⁶⁵ '' Leu Wall 170 Leu Phe Ser Asn Lys Ser ¹⁷⁵ Leu Ser Gin Glu 180 Ile Leu '· · ‘‘ l Ala 185 Gin Lys Gly Asn Gin Asn Gly Val 195 Phe Glu Leu Asn '200 Leu Tyr Asn Gly His Ala Tyr Phe  :, 205; Thr Gin Gly Asp 210; Lys Met, Arg Lys' / 215 Wall Asp Phe. Glu Glu Leu His Leu i 220 Arg 225 Asn Lys Leu Lys Ser Phe Ash 230 ' Ser Asn Asp Ala Ala Tyr Leu Gin 235 in 240

• 0 0 • • 0 0 '0' · 0 0 0 · '· 1 00. »'· 0 • · • 0 0 * · ·· 0 • 0 -.0 0 0 '0 0 0 0 0 0 0 9 0

197

Gly Thr Asp Tyr Leu Gly Tyr Trp Lys ²⁴⁵

Asn Lys Asn Gin Arg Arg Phe Ser

250 -255

Gin Ala Ile Leu

260, 265, 270

Phe For Leu Ala Ser Wall Phe Leu Ile For Leu-Phe Gly Ile Ala Asn 275 · 280 285 For Arg Phe Lys Thr Asn Trp Ser Tyr Phe Leu Gly Ala Wall. 290 295 300 '.Gly > Val ’ Tyr'Phe Leu Met. Wall His Wall· Ile Ser * .Thr .. ' .Asp Leu Phe .Leu • 305 310 315 '320 Met Thr Phe Phe For Phe, Ile- Trp .'Ala..řPhe, 'Ila. iSer '.Tyr. .Leu • .Leu ' ³²⁵ 330 ' . , 335 , Phe Arg Lys Phe Ile Leu Lys Arg Tyr

340 345 (2) Information for SEQ ID NO: 77:

(i) Sequence characteristics:

(A) Length: 276 amino acids (B) Type: amino acid (D) Topology: linear (ii) Molecule type: protein (iii) Hypothetical: YES ..

(vi) Original source:. · '-' (A) Organism: Helicobacter pylori (ix) Properties:

(A) Name / Key: misc_charakter (B) Location: 1 ... 276 (xi) Sequence Description: SEQ ID NO: 77:

Met Lys Lys Lys Ala Lys Wall Phe Trp Cys Cys Phe Lys Met Ile Arg 1 5 10 15 Dec Trp Leu Tyr Leu Ala Wall Phe- Phe Leu Leu Ser Wall Ser Asp Ala Lys 20 May 25 3 0 Glu Ile Ala Met Gin Arg Phe Asp Lys Gin Asn His Lys Ile Phe Glu 35 40 45 Ile Leu Ala Asp Lys Wall Ser Ala Lys Asp Asn Wall Ile Thr Ala Ser 50 55 60 Gly Asn Ala Ile Leu Leu Asn Tyr Asp Wall Tyr Ile Leu Ala Asp Lys 65 70 75 80 Wall Arg Tyr Asp Thr Lys Thr Lys Glu Ala Leu Leu Glu Gly Asn Ile 85 90 95 Lys Wall Tyr Arg Gly Glu Gly Leu Leu Wall Lys Thr Asp Tyr Wall Lys 100 ALIGN! 105 110 Leu Ser Leu Asn Glu Lys Tyr Glu Ile Ile Phe For Phe Tyr Wall Gin 115 - 120 125 Asp Ser Wall Ser Gly Ile Trp Wall Ser Ala Asp • Ile Ala Ser Gly Lys 130 135  L 140 Asp Gin Lys Tyr Lys Ile Lys Asn Met Ser Ala · . Ser, Gly Cys Ser Ile 145 150 155 160 Asp Asn For Ile Trp., His wall Asn Ala Thr ' Ser Gly Ser Phe Asn Met 165- ' ! , í 170 * 175 Gin' Lys Ser His Leu Ser Met ‘ in Trp Asn Pro Lys Ile · Tyr •> Wall Gly Asp

180 ··· «

·· · · · • «· • · · · • 9 • 9 9 9 9 · · •> ··· 198 9 · · • • ·

Ile For Wall 195 Leu Tyr Leu For Tyr 200 Arg Thr 210 Thr Gly Phe Leu Tyr 215 For Gly 225 Phe Ile > Tyr Leu Gin '230 For Phe Asp Meh. Thr Phe : Thr 245 For Gin Ile Asn. Cys > Phe Ala Glu Leu Ala 260 Phe Arg Tyr Ile Asn

'275

185 190 Ile Phe Met Ser Thr Ser 205 Asn Lys Glu Phe Gly Thr 220 Ser Asn Leu Asp Tyr Leu Ala '235 For. Lys Asn Ser Trp 240 Arg Tyr . Lys: • Arg / ; Gly'.Phe .Gly Leu ' 250 *: , 255 Ser 265 Lys Thr Gin Val Phe / Ile Gin

(2) Information for SEQ ID NO:

(i) Sequence characteristics:

(A) Length: 224 amino acids (B) Type: amino acid (D) Topology: linear (ii) Molecule type: protein (iii) Hypothetical: YES (vi) Original source:

(A) Organism: Helicobacter pylori (ix) Properties: '(A) Name / Key: misc_character (B) Location: 1 ... 224 (xi) Sequence Description: SEQ ID NO: 78:

Met 1 Ile Arg Leu Lys 5 Gly Leu Asn Lys Thr 10 Leu Lys Thr Ser Leu 15 Dec Leu Ala Gly Wall Leu 20 May Leu Gly Ala Thr Ala 25 For Leu Met Ala Lys 30 For Leu Leu Ser Asp 35 Glu Asp Leu Leu Lys 40 Arg Wall Lys Leu His 45 Asn Ile Lys Glu Asp 50 Thr Leu Thr Ser Cys 55 Asn Ala Lys Wall Asp 60 Gly Ser Gin Tyr Leu 65 Asn Ser Gly Trp Asn 70 Leu Ser Lys Glu Phe 75 For Gin Glu Tyr Arg 80 Glu Lys Ile Phe Glu 85 Cys .Wall Glu Glu Glu 90 Lys His Lys Gin Ala 95 Leu Asn Leu Ile Asn 100 ALIGN! Lys Glu Asp Thr Lys Asp Lys Glu Glu Leu 110 Ala Lys Lys Ile Lys 115 Glu Ile Lys Glu Lys 120 Ala Lys Wall Leu Arg 125 Gin Lys Phe Met Ala 130 Phe Glu Met Lys Glu 135 His Ser Lys Glu Phe 140 For Asn Lys Lys Gin 145 Leu Gin Thr Met Leu 150 Glu Asn and; Ala Phe Asp 155 Asn Gly Ala Glu Ser 160 Phe Ile Asp Asp Trp His Glu Arg Phe Gly Gly • Tle Ser Arg Glu Asn

·· ·

199 ·· • 9 · φ t · t · · · · · · · · · · · · · ·

Γ t · * 4 4 4 4 4 4 4

- ♦ '«··., 165,170,175

Thr Tyr Lys Ala Leu Gly Ile Lys Glu Tyr Sher Asp Glu Gly Lys -Ile '

180. .. · 185. · · 190., Leu Pro 'Leu Ala' · Lys Glu .Val Ile. Leu Asp Asn, Ile. ^; , Lys ;; Lys.; Ile \ Leu

195 '' 200 205,,

Lys Lys Ala Leu, Met Asle Leu, Asp Asn For Tyr Leu Leu Trp Leu Val

- 210,215 · ·. 220 (2) Information for SEQ ID NO: 79:

-— (i) Sequence characteristics: ~ (A) Length: 429 amino acids (B) Type: amino acid (D) Topology: linear (ii) Molecule type: protein (iii) Hypothetical: YES (vi) Original source:

(A) Organism: Helicobacter pylori (ix) Properties:, (A) Name / Key: misc_character (B) Location: 1 ... 429 (xi) Sequence Description: SEQ ID NO: 79:

Met For Tyr Ala Leu Arg Lys Arg Phe Phe Lys Arg Leu Leu Leu Phe 1 5 10 15 Dec Phe Leu Ile Wall Cys Met Ile Asn Leu His Ala Lys Ser Tyr Leu Phe 20 May 25 30 Ser For Leu For For Ala His Gin Gin Ile Ile Lys Thr Glu For Cys 35 40 45 Ser Leu Glu Cys Leu Lys Asp Leu Met Leu Gin Asn Gin Ile Phe Ser 50 55 60 Phe Wall Ser Gin Tyr Asp Asp Asn Asn Gin Asp Glu Ser Leu Lys Thr 65 70 75 80 Tyr Tyr Lys Asp Ile Leu Asn Lys Leu Asn For Wall Phe Ile Ala Ser 85 90 95 Gin Thr For Ala Lys Glu Ser Tyr Glu For Lys Ile Glu Leu Ala Ile 100 ALIGN! 105 110 Leu Leu For Lys Lys Wall Wall Gly Arg Tyr Ala Ile Leu Wall Met Asn ¹¹⁵ 120 125 Thr Leu Leu Ala Tyr Leu Asn Thr Arg Asn Asn Asp Phe Asn Ile Gin 130 135 140 Wall Phe Asp Ser Asp Glu ' Glu Ser Pro Glu Lys Leu Glu Glu Thr Tyr 145 150 155 160 Lys Glu Ile Glu Lys Glu ' Lyš Phe Pro Phe Ile Ile. Ala Leu Leu Thr 165 170 175 Lys Glu Gly Wall Glu Asn, Leu Leu Gin Asn Thr, Thr ile Asn Thr For 180 V ', 185 190 Thr Tyr Wall For Thr. Wall Asn Lys' Thr Gin Leu Glu Asn His Thr Glu • · í 195 200 :: 205 Leu Ser Leu Ser Glu- Arg Leu. Tyr Phe Gly Gly: Ile Asp , u · Tyr Lys Glu

2Po · ·: ::

• · ·

··· • · · · • · • 1 »· · 210 215 220 Gin Leu Gly Met Leu Ala Thr Phe Ile Ser For Asn Ser For Wall Ile 225 230 235 240 Glu Tyr Asp Asp Asp Gly Leu Ile Gly Glu Arg Leu Arg Gin Ile Thr 245 250 255 Glu .Ser Leu • Asn Wall Glu Wall Lys His Gin Glu Asn Ile Ser Tyr Lys 260 265 270 Gin Ala . Thr Ser Phe Ser Lys Asn Phe Arg Lys His Asp Ala .. Phe .Phe 275 280 285 Lys Asn Ser Thr Leu Ile Leu Asn Thr For Thr Thr Lys. Ser Gly Leu 290 295 300 Ile Leu Ser Gin Ile Gly, Leu Leu Glu Tyr Lys -For .Leu Lys Ile Leu 305 310 315 320 Ser Thr, .Gin Ile Asn Phe Asn For Ser Leu Leu iLeu; Leu 'Thr Gin For 32S 330 335 Lys Asp Arg Lys Asn Leu ^- Phe Ile Wall Asn Ala Leu Gin Asn Ser Asp 340 ....... _____ Glu Thr Leu Ile Glu Tyr Ala Ser Leu Leu Glu Ser Asp 350 Leu Arg His 355 360- 365 Asp Trp Wall Asn Tyr Ser Ser Ala Ile Gly Leu Glu Met Phe Leu Asn 370 375 380 Thr Leu. Asp For His Phe Lys Lys Ser Phe Gin Glu Ser Leu Glu Asp 385 390 395 400 Asn Gin Wall Arg Tyr His Asn Gin Ile Tyr Gin Ala Leu Gly Tyr Ser 405 410 415 Phe Glu For Ile Lys Asn Glu Ser Glu Thr Lys Lys Glu

420

(2) Information for SEQ ID NO: 80:

(i) Sequence characteristics:

(A) Length: 455 amino acids (B) Type: amino acid (D) Topology: linear (ii) Molecule type: protein (iii) Hypothetical: YES (vi) Original source:

(A) Organism: Helicobacter pylori (ix)

(A) Name / Key: misc_charakter (B) Location: 1 ... 455 (xi) Sequence Description: SEQ ID NO: 80:

Wall Leu Lys Phe Gin Lys Leu For Leu Leu Phe Wall Ser Ile Leu Tyr 1 5 10 IS Asn Gin Ser For Leu Leu Ala Phe Asp Tyr Lys Phe Ser Gly Wall Ala 20 May 25 30 Glu Ser Wall Ser Lys Wall Gly Phe Asn His Ser Lys Leu Asn Ser Lys 35 40 45 Glu Gly Ile Phe For Thr Ala Thr Phe wall Thr Ala Thr Ile Lys Leu

50 55 60 Gin Wall Asp Ser.Asn Leu Leu For. Lys Asn Ile Glu Lys His Ser Leu 65 70 75 80 Lys : ile Gly Wall. Gly. Gly Ile. Leu Gly. Ala Leu Ala- Tyr Asp .Ser, Thr 85 90 95 Lys Thr Leu Ile ' Asp Gin Ala Thr His Gin' Ile Tyr .Gly Ser Glu Leu 100 ALIGN! 105 . 110 Phe Tyr Leu Ile Gly Arg Trp. .Trp Gly Phe: Leu Gly / Asn; Ala For Trp 115. 120 - , 125 Lys Asp Ser. Leu , Ile, Glu: Ser- Asp Ala- His Thr Arg Asn Tyr Val _: Leu 130 135 . , 140 Tyr Asn Ser Tyr «Leu Phe , Tyr Ser Tyr Gly Asp Lys Phe / His Leu Lys 145 150 155 160 Tjf »u Glv Aro Tyr. Leu Ser Asn Met Asp Phe Met Ser Ser Tyr Thr Gin 165 170 175 ·. Gly Phe Glu Leu Asp Tyr Lys Ile Asn Ser Lys Ile Ala Leu Lys Trp 180 185 190 Phe Ser Ser Phe Gly Arg Ala Leu Ala Phe Gly Gin Trp, Ile. Arg Asp 195 200 205 Trp Tyr. Ala For' Ile Wall Thr Glu Asp Gly Arg Lys Glu Val Tyr Asp 210 215 220 Gly Ile His Ala Ala Gin Leu Tyr Phe Ser Ser Lys His Val Gin Wall 225 230 235 240 Met For Phe Ala Tyr Phe Ser For Lys Ile Tyr Gly Ala Pro Gly Wall 245 250 255 Lys Ile His Ile Asp Ser Asn For Lys Phe Lys Gly Leu Gly Leu Arg 260 265 270 Ala Gin Thr Thr Ile Asn Wall Ile Phe For Wall Tyr Ala Lys Asp Leu 275 280 285 Tyr Asp Wall Tyr Trp Arg Asn Ser Lys Ile Gly Glu Trp Gly Ala Ser 290 295 300 Leu Leu Ile His Gin Arg Phe Asp Tyr Asn Glu Phe Asn Phe Gly Phe 305 310 315 320 Gly Tyr Tyr Gin Asn Phe Gly Asn Ala Asn Ala Arg Ile Gly Trp Tyr 325 330 335 Gly Asn For Ile For Phe Asn Tyr Arg Asn Asn Ser Val Tyr Gly Gly 340 345 350 Wall Phe Ser Asn Ala Ile Thr Ala Asp Ala Wall Ser Gly Tyr Wall Phe 355 360 365 Gly Gly Gly Wall Tyr Arg Gly Phe Leu Trp Gly Ile Leu Gly Arg Tyr 370 375 380 Thr Tyr Ala Thr Arg Ala Ser Glu Arg Ser Ile Asn Leu Asn Leu Gly 385 390 395 400 Tyr Lys Trp Gly Ser Phe Ala Arg Wall Asp Wall Asn Leu Glu Tyr Tyr 405 410 415 Wall Wall Ser Met His Asn Gly Tyr Arg Leu Asp Tyr Leu Thr Gly For 420 425 430 Phe Asn Lys Ala Phe Lys Ala Asp Ala Gin Asp Arg Ser Asn Leu Met 435 440 445 Wall Ser Met Lys Phe Phe Phe -

450 455

(2) Information for SEQ ID NO: 81:

(i) Sequence characteristics:

(A) Length: .482 amino acids (B) Type: amino acid -. (D) Topology: linear. (ii) Molecule type / -protein (iii) Hypothetical: YES (vi) Original source:

‘- (A) Organism: Helicobacter pylori ----------------------------- (ix) Properties:

(A) Name / Key: misc_character (B) Location: 1 ... 282 (xi) Sequence Description: SEQ ID NO: 81:

Met Gly Cys Ser Phe Ile Phe Lys Lys Wall Arg Wall Tyr Ser Lys Met 1 5 10 15 Dec Leu Wall Ala Leu Gly Leu Ser Ser Wall Leu Ile Gly Cys Ala Met Asn 20 May 25 30 For Ser Ala Glu Thr Lys Lys- For Asn Asp Ala Lys Asn Gin Gin For 35 40, 45 Wall Gin Thr His Glu Arg Met Thr Thr Ser Ser Glu His Wall Thr For 50 55 60 Leu Asp Phe Asn Tyr For Wall His Ile Wall Gin Ala For Gin Asn His 65 70 75 80 His Wall Wall Gly Ile Leu Met For Arg Ile Gin wall Ser Asp Asn Leu 85 90 95 Lys For Tyr Ile Asp Lys Phe Gin Asp Ala Leu Ile Asn Gin Ile Gin 100 ALIGN! 105 110 Thr Ile Phe Glu Lys Arg Gly Tyr Gin Wall Leu Arg Phe Gin Asp Glu 115 120 125 Lys Ala Leu Asn Wall Gin Asp Lys Lys Lys Ile Phe Ser Wall Leu Asp 130 135 140 Leu Lys Gly Trp Wall Gly Ile Leu Glu Asp Leu Lys Met Asn Leu Lys 145 150 155 160 Asp For Asn Ser For Asn Leu Asp Thr Leu Wall Asp Gin Ser Ser Gly 165 170 175 Ser Wall Trp Phe Asn Phe Tyr Glu For Glu Ser Asn Arg Wall Wall His 180 185 190 Asp Phe Ala Wall Glu Wall Gly Thr Phe Gin Ala Ile Thr Tyr Thr Tyr 195 200 205 Thr Ser Thr Asn Asn Ala Ser Gly Gly Phe Asn Ser Ser Lys Ser Wall 210 215 220 Ile His Glu Asn Leu Asp Lys Asn Arg Glu Asp Ala Ile His Lys Ile 225 230 235 240 Leu Asn Arg Met Tyr Ala Wall Wall Met Lys Lys Ala Wall Thr Glu Leu 245 · 250 255 Thr Lys Glu Asn Ile Ala Lys Tyr Arg Asp, Ala Ile Asp Arg Met Lys 260 265 ₄ 270 Gly Phe Lys Ser Ser Have 'Pro Gin Lys Lys * 275 280 -

• ·

2CX3) Information for SEQ ID NO: 82:

. (i) Sequence characteristics:

(A) Length: 280 amino acids (B) Type: amino acid (D) Topology: linear (ii) Molecule type: protein (iii) Hypothetical: YES (vi) Original source:

- (- Aj — Grgani-smus -: - Hei-icobacter ^ pylori (ix)

(A) Name / Key: misc_charakter (B) Location: 1 ... 280 (xi) Sequence Description: SEQ ID NO: 82:

Met Lys Leu Arg Ala Ser Gly Val Ala Ile Leu Cys Leu 1 5 10 15 Dec Ile Leu Ser Ala Cys Ser Asn Tyr Ala Lys Val Lys Gin Lys 20 May 25 30 Asn His Val Tyr Thr Pro Val Tyr Asn Glu Leu Ile Glu Lys Tyr Ser 35 40 45 Glu Ile For Leu Asn Asp Lys Lys Asp Thr Pro Phe Met Wall Gin 50 55 60 Val Lys Leu Asn Tyr Lys Asp Tyr Leu Leu Asp Asn Lys Gin Wall 65 70 '75 80 Val Leu Thr Leys Val His Serys Lys Lys Ile Thr Leu Ile 85 90 95 Gly Asp Ala Asn Lys Ile Leu Gin Tyr Lys Asn Tyr Phe Gin Ala Asn 100 ALIGN! 105 110 Gly Ala Arg Asp Ile Asp Phe Tyr Leu Gin Thr Leu Asn Gin 115 120 125 Lys Gly Val Met Ile Ala Ser Asn Tyr Asn Asp Asn Pro Asn Asn 130 ¹³⁵ 140 Lys Glu Lys Pro Gin Thr Phe Asp Val Leu Gin Ser Gin For Met 145 150 155 160 Gly Ala Asn Thr Lys Asn Leu His Gly Tyr Asp Val Ser Gly Ala 165 170 175 Lys Gin Val Ile Asn Glu Val Ala Lys Ala Gin Leu 180 185 190 Glu Lys Ile Asn Gin Tyr Tyr Lys Thr Leu Leu Gin Asp Lys Glu Gin 195 200 205 Glu Tyr Thr Thr Arg Lys Asn Asn Gin Arg Glu Ile Leu Glu Thr Leu 210 215 220 Ser Asn Arg Ala Gly Tyr Gin Met Arg Gin Asn Val Ile Ser Ser Glu 225 230 235 240 Ile Phe Lys Asn Gly Asn Leu Asn Met Gin Ala Lys Glu Glu Glu Wall 245 250 255 Arg Glu Lys Leu Gin Glu Glu Arg Glu Asn Glu Tyr Leu Arg Asn Gin 260 265 270 Ile Arg - Ser Leu Leu Ser Gly Lys

275 280 ·· ····

64 • • tt · (2) Information for SEQ ID NO: 83:

(i) Sequence characteristics:

(A) Length: 393 amino acids (B) Type: amino acid (D) Topology: linear (ii) Molecule type: protein (iii) Hypothetical: YES (vi) .Original source:

(A) Organism: Helicobacter pylori (ix) · Features: (A) Name / Key: (B) Location: 1 (xi) Sequence description: misc_charakter ... 393 SEQ ID NO: 83 Met 1 Arg Lys Leu Phe Ile Pro 4 Leu Leu Leu Leu Glu 15 Dec Ala Asn Glu Lys Asn Gly Phe Phe Ile Glu Ala Gly Phe Glu Thr 30 Gly Leu Leu Glu Gly Thr Gin Glu Lys Arg His Thr Thr. 40 45 Thr Lys Asn Thr Tyr 50 Ala Thr Tyr Asn Tyr 56 Leu Pro Thr Asp Thr Ile Leu Lys Arg Ala 65 Ala Asn Leu Phe Thr Asn 70 Ala Glu Ala Ile Ser Lys Leu Lys Phe 80 Ser Ser Leu Ser Pro Val Arg Val Leu Tyr Met Tyr Asn 89 Gly Gin 95 Leu Thr Ile Glu Asn Phe Leu Pro Tyr Asn Leu Asn Val 105 Lys 110 Leu Ser Phe Thr Asp Ala Gin Gly Asn 114 Val Ile Asp Leu Gly Val 120 Ile Glu Thr Ile For 130 Lys His Ser Lys Ile Val Leu Pro Gly Glu Al 140 Phe Asp Ser Leu 145 Lys Ile Asp Pro Tyr Thr 150 Leu Phe Leu For Lys Ile 155 Glu Ala Thr 160 Ser Thr Ser Ile Ser Asp Ala Asn Thr Gin Arg Val Phe Glu Thr 175 Leu Asn Lys Ile Lys Thr Asn Leu Val Val Asn Tyr Arg Asn Glu 190 Asn Lys Phe Lys Asp His Glu Asn His 195 Trp Glu Ala Phe Thr Pro 200 205 Gin Thr Ala Glu Glu 210 Phe Thr Asn Leu Met Leu Asn Met Ile Ala.Val Leu Asp Ser Gin 225 Ser Trp Gly Asp Ala Ile ²³⁰ Leu Asn Ala Pro Phe. Glu 235 ' Phe Thr Asn 240 Ser For Thr Asp Cys Asp Asn 244 Asp Lys Cys Val 250 Asn For Gly 255 Thr Asn Gly Leu Val Asn Ser 260 Lys Val Asp Gin Lys Tyr Wall 270 Leu Asn

Lys Gin Asp Ile Val Asn Lys Phe Lys Asn. Lys Ala Asp Leu Asp Val 275 280 285 Ile Wall Leu Lys Asp Ser Gly Wall Wall Gly Leu Gly Ser Asp Ile Thr 290 295 300 For Ser Asn Asn Asp Asp Gly Lys His Tyr Gly Gin Leu Gly Wall Wall 305 310 315 - 320 Ala Ser Ala Leu Asp For Lys Lys Leu Phe Gly Asp Asn Leu Lys Thr 325 330 335 Ile Asn Leu Glu Asp Leu Arg Thr Ile Leu His Glu Phe Ser His Thr * 340 345 350 Lys Gly Tyr Gly His Asn Gly Asn Met Thr Tyr Gin Arg Wall For Wall 355 360 365 Thr Lys Asp Gly Gin Wall Glu Lys Asp Ser Asn Gly Lys For Lys Asp 370 375 380 Ser Asp‘Gly Leu For Tyr Asn Wall Cys 385 390

(2) Information for SEQ ID NO: 84:

(i) Sequence characteristics:

(A) Length: 270 amino acids (B) Type: amino acid (D) Topology: linear (ii) Molecule type: protein (iii) Hypothetical: YES ^; (vi) Original source:

(A) Organism: Helicobacter pylori (ix)

(A) Name / Key: misc_charakter (B) Location: 1 ... 270

(xi) Description SEQ ID NO: 84: Met 1 Lys Lys Phe Val Ala Leu Gly Leu Leu Ser Ala Val Leu Seru 5 10 15 Ser Leu Leu Ala 20 May Glu Gly Asp Gly Thr Asle Tyr Gin 25 30 Leu Gly Gin Ala Arg Leu Asn Ser Asn Ir Tyr Thr Gly Asp Cys 40 45 Thr Gly Ser Val Val Gly Cys Pro Gly Leu Thr Ala Asn Lys His 55 Asn 65 For Gly Gly Thr Asn Ile Asn Trp His Ser Ala Leu Asn Gly Phe Gly Leu Asn Val Gly Tyr Lys Phys Phe Gin 85 90 95 Phe Lys Ser Leu Asp Met Thr Lys Trp Phe Gly Phe Arg Val Tyr 105 110 Gly Leu Phe Asp 115 Tyr Gly His Ala Asp Leu Gly Lys Gin Val For Asn Lys Ile Gin Leu Asp Met Val Ser

• ·· ··················

Leu Leu Ala Asp Ile Ile Asp Lys Asp Asn Ala Ser 145 ISO 155 . Glý Gly Wall Ala Ile Gly Gly Asn Thr ‘Trp Lys Ser 165 170 Tyr Trp Lys Glu Gin Ile Ile Glu Ala Lys Gly For 180 185 For Thr Tyr Cys Asn For Asn Ala For Tyr Ser Thr 195 200 Wall Ala Phe Gin Wall Trp Leu Asn Phe Gly Wall Arg 210 215 220 Lys His Asn Gly Wall Glu Phe Gly Wall Arg Wall For '225 230 235 Lys Phe. Leu Ser Ala Gly For Asn Ala Thr Asn Leu 245 250 Lys Arg Asp Tyr Ser Leu Tyr Leu Gly Tyr Asn Tyr 260- 265

Phe

Ser

Asp

Asn

205

Ala

Leu

Tyr

Thr

Gly

Ala

Wall

190

Thr

Asn

Leu

Tyr

Phe

270

Ile

Ala

175

Cys

Ser

Ile

Ile .His

255

Phe

160

Asn

Thr

Thr

Tyr

Asn

240

..Leu (2) Information for SEQ ID NO: 85:

(i) Sequence characteristics:

(A) Length: 140 amino acids (B) Type: amino acid (D) Topology: linear (ii) Molecule type: protein (iii) Hypothetical: YES (vi) Original source:

(A) Organism: Helicobacter pylori (ix)

(A) Name / Key: misc_character (B) Location: 1 ... 140

(xi) Description sequence: SEQ ID NO: 85: Met His Pro Ile Met Phe Ala Tyr Ile Ala Asn Ala Leu Gin Ala 1 5 10 15 Dec Arg Lys Ile Asn Gly Thr Leu Cys Met Ala Phe Gin Lys 20 May 25 30 Wall Lys Glu Leu Gly Ile Asp Lys Ala Lys Ser Leu Ile Gly Asn Leu 35 40 45 Ser Gin Val Ile Ile Tyr Pro Thr Lys Asp Thr Asp Glu Leu Ile Glu 50 55 60 Cys Gly Val Pro Leu Ser Asp Ser Glu Ile Asn Phe Leu His Asn Thr 65 70 75 80 Asp Met Arg Ala Gin Val Leu Wall Lys Asn Ile Val Thr 85 90 95 Ser Ala Phe Ile Glu Ile Asp Leu Lys Lys Ile Cys Lys Asn Tyr Phe 100 ALIGN! 105 110 Ile Phe Leu Ala Met Leu Val Ile Glu Lys Ser Ser Met by Ile Leu 115 120 125 Lys Lys Gin Thr Lys Lys Leu Ile Arg Lys Ser Ile 130 ¹³⁵ 140

20 * 7,

(2) Information for SEQ ID NO: 86:

(i) Sequence characteristics:

(A) Length: 256 amino acids (B) Type: amino acid (D) Topology: linear (ii) Molecule type: protein (iii) Hypothetical: YES (vi) Original source:

(A) Organism: Helicobacter pylori (ix)

(A) Name / Key: misc_charakter (B) Location: 1 ... 256 (xi) Sequence Description: SEQ ID NO: '86:

Met Leu Gly Ser Wall Lys Lys Ala Val Phe. Arg Val Leu Cys Leu Gly 1 5 \ 10 /. »» 15 Dec Cys Leu Cys Gly Gly Leu Met Ala Gin Asp For Lys Glu 20 May . 25 30 Leu Ile Phe Gly Ile Thr Ile Tyr Thr Asp Lys Asn Phe Thr Arg 35 40 45 Ala Lys Lys Tyr Phe Glu Lys Ala Cys Lys Asn Asp Ala Asp Gly 50 55 60 Cys Ala Ile Leu Arg Glu Wall Tyr Ser Ser Gly Lys Ala Ile Ala Arg 65 70 75 80 Glu Asn Ala Arg Glu Ser Ile Glu Lys Ala Leu Glu His Thr Ala Thr 85 90 95 Ala Lys Lys Leu Asn Asp Ala Glu Lys Cys Lys Asp Leu Ala 100 ALIGN! 105 110 Glu Phe. Tyr Phe Asn Wall Asn Asp Leu Lys Asn Ala Leu Glu Tyr Tyr 115 120 125 Ser Cys Ser Cys Lys Leu Asn Asn Val Glu Cys Met Leu Ser Ala 130 135 140 Thr Phe Tyr Asn Asp Met Ile Lys Gly Leu Lys Asp Lys Lys Asp 145 150 155 160 Leu Glu Tyr Tyr Ser Lys Ala Cys Glu Leu Asn Asn Gly Gly Gly Cys 165 170 175 Ser Lys Leu Gly Gly Asp Tyr Gly Glu Gly Val Thr Lys Asp 180 ¹⁸⁵ 190 Phe Lys Lys Ala Phe Glu Tyr Ser Ala Lys Ala Cys Glu Leu Asn Asp 195 200 205 Ala Lys Gly Cys Tyr Ala. Leu · Ala Ala Phe Tyr Asn Glu Gly Lys Gly 210 215 .220 Val Ala Lys Asp Glu Lys Gin Thr Thr Glu Asn Leu Glu Lys Ser Cys 225 230 '235 ^hp ·'  ' 240 Lys Leu Lys Glu Ala Cys Asp Ile Leu Lys Glu Gin Lys Gin 245 250 • ... * 255

and.

(2) Information for SEQ ID NO: 87:

(i) Sequence characteristics:.

(A) Length: 242 amino acids,, (B) Type: amino acid. *, (D) Topology: alcohol (ii) Molecule type: protein. (iii) Hypothetical: YES., (vi) Original, Source:

______ (A) —Organ-i-smue -: - Hel-ieobacter-pylOri (ix)

(A) Name / Key: misc_character (B) Location: 1 ... 242 (xi) Sequence Description: SEQ ID NO: 87:

Met 1 Lys Lys Phe Phe 5 Ser Gin Ser Leu Leu 10 · Ala Leu Ile Ile Ser 15 Dec Met Asn Ala Wall Ser 20 May Gly Met Asp Gly Asn Gly 25; · - ’ Val 'Phe - _to :: Leu Gly 30 Ala Gly Tyr Leu Gin 35 Gly , Gln Ala Gin Met- 40 ' His Ala Asp ' Ile Asn 45 Ser Gin Lys Gin Ala 50 Thr Asn Ala Thr Ile 55 Lys Gly Phe Asp Ala 50 Leu Leu Gly Tyr Gin 65 Phe Phe Phe Glu Lys 70 His Phe Gly Leu Arg 75 Leu Tyr Gly Phe Phe 80 Asp Tyr Ala His Ala 85 Asn Ser Ile Lys Leu 90 Lys Asn For Asn Tyr 95 Asn Ser Glu Ala Ala 100 ALIGN! Gin Wall Ala Ser Gin 105 Ile Leu Gly Lys Gin 110 Glu Ile Asn Arg Leu 115 Thr Asn Ile Ala Asp 120 For Arg Thr Phe Glu 125 For Asn Met Leu. Thr 130 Tyr Gly Gly Ala Met 135 Asp Wall Met Wall Asn 140 Wall Ile Asn Asn Gly 145 Ile Met Ser Leu Gly 150 Ala Phe Gly Gly Ile 155 Gin Leu Ala Gly Asn 150 Ser Trp Leu Met Ala 165 Thr For Ser Phe Glu 170 Gly Ile Leu Wall Glu 175 Gin Ala Leu Wall Ser 180 Lys Lys Ala Thr Ser 135 Phe Gin Phe Leu Phe 190 Asn Wall Gly Ala Arg 195 Leu Arg Ile Leu Lys 200 His Ser Ser Ile Glu 205 Ala Gly Wall Lys Phe 210 For Met Leu Lys Lys 215 Asn For Tyr Ile Thr 220 Ala Lys Asn Leu Asp 225 Ile Gly Phe Arg Arg 230 Wall Tyr Ser Trp Tyr 235 Wall Asn Tyr Wall Phe 240

Thr Phe · · «· ·

20? (2) Information for SEQ ID NO: 88:

(i) Sequence characteristics:

(A) Length: 267 amino acids (B) Type: amino acid (D) Topology: linear (ii) Molecule type: protein (iii) Hypothetical: YES (vi) Original source:

- (A) Organism: Helicobacter pylori ------ (ix) Properties:

(A) Name / Key: misc_charakter (B) Location: 1 ... 267 (xi) Sequence Description: SEQ ID NO: 88:

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

«0 0 · ·

W / *

0 * 0 0000

0 «0000

(2) Information for SEQ ID NO: 89:

(i) Sequence characteristics:

(A) Length: 544 amino acids

- (B) Type: amino acid (D) Topology: linear · (ii) Molecule type: protein (iii) Hypothetical: YES (vi) Original source:

- · —_ (A) —Organism -: - Hel-i-cobacter ^ pylori '(ix) Features:

(A) Name / Key: misc_character (B) Location: 1 ... 544

(xi) Description sequence: SEQ ID NO: 89: Wall '1 Ile Glu Thr Ile Pro Lys His Ser Lys 10 Ile Val Leu Gly Glu 15 Ala Phe Asp Ser Leu Lys Glu Ala Phe 25 Asp Lys Ile Asp Pro Tyr Thr Phe Phe Phe Pro 35 Lys Phe Glu Ala Thr Ser Thr Ser Ile Ser Asp Thr Asn Thr Gin Arg Val Phe Glu Thr · 55 Leu Asn Asn Ile Lys Thr Ile 65 Met Lys Tyr Ser Asn Glu Asn 70 For Asn Asn Phe Asn Thr Cys Pro 75 Tyr Asn Asn Asn Gly Asn Thr Lys Asn Asp 90 Cys Trp Gin Asn Phe Thr For Gin Thr Ala 100 ALIGN! Glu Glu Phe Thr Asn 105 Leu Met Leu Asn Met Ile Ala 110 Wall Leu Asp Ser 115 Gin Ser Trp Gly Asp 120 Ala Ile Leu Asn Ala Pro Phe 126 Glu Phe Thr Asn 130 Ser Ser Thr Asp 135 Cys Asp Ser Lys Cys 140 Wall 145 Asn Pro Gly Val Asn Gly Arg Wall Asp Thr Lys Val Asp Gin Gin 155 Tyr Ile Leu Asn Lys Gin Gly Ile Ile Asn 170 Asn Phe Arg Lys Lys Ile Glu Ile Asp Ala Val Leu Lys Asn 185 Ser Gly Val Val Gly Leu Ala 190 Asn Gly Tyr Gly Asn Asp Gly Glu 200 Tyr Gly Thr Leu Gly Val Glu Ala Tyr Ala Leu Asp 210 For Lys Lys Leu 215 Phe Gly Asn Asp Leu Lys Thr Ile Asn 225 Leu Glu Asp Leu Arg Thr Ile 230 Leu His Glu Phe Ser His Thr Lys 235,240 Gly Tyr Gly His Asn Gly Asn Met ²⁴⁵ Thr Tyr 250 Gin Arg Val Pro Val Thr 255 Lys Asp Gly Gin Val Glu Lys Asp Ser 265 Asn Gly Lys for Lys Asp Ser 270 Asp Gly Leu Pro Asr Val Cys 280 Ser Leu Tyr Gly Gly Ser Asn Gin 285 ' For Ala Phe Pro 290 Ser Asn Tyr Pro 295 Asn Ser Ile Tyr His Asn Cys Ala

• <1 · ·

• ·· ·· • · • · 41 • · • · Asp 305 Wall For Ala Gly Phe 310 Leu Gly Wall Thr Ala 315 Ala Wall Trp Gin Gin 320 Leu Ile Asn Gin Asn 325 Ala Leu For Ile Asn 230 Tyr Ala Asn Leu Gly 335 Ser Gin Thr Asn Tyr 340 Asn Leu Asn Ala Ser 345 Leu Asn Thr Gin Asp 350 Leu Ala Asn -Ser Met 355 Leu Ser Thr Ile Gin 360 Lys Thr Phe Wall Thr 365 Ser Ser Wall Thr * Asn 370 His His Phe ? Ser Asn 375 Ala Ser Gin Ser Phe 380 Arg Ser for Ile Leu 385 Gly Wall Asn Ala Lys 390 Ile Gly Tyr. Gin Asn 395 Tyr Phe Asn Asp Phe 400 Ile Gly Leu Ala Tyr 405 Tyr Gly Ile Ile Lys 410 Tyr Asn Tyr. Ala Lys 415 Ala Wall Asn Gin' Lys 420 Wall Gin Gin Leu Ser 425 Tyr Gly Gly Gly Ile 430 Asp Leu Leu Leu Asp 435 Phe Ile Thr Thr Tyr 440 Ser Asn Lys Asn Ser 445 For Thr Gly .Ile Gin 450 Thr Lys Arg Asn Phe 455 Ser Ser Ser Phe Gly 460 Ile Phe Gly Gly Leu 465 Arg Gly Leu Tyr Asn 470 Ser Tyr Tyr Wall Leu 475 Asn Lys Wall Lys Gly 480 Ser Gly Asn Leu Asp 485 Wall Ala Thr Gly Leu 490 Asn Tyr Arg Tyr Lys 495 His Ser Lys Tyr Ser 500 Wall Gly Ile Ser Ile 505 For Leu Ile ' Gin Arg 510 Lys Ala Ser Wall Wall 515 Ser Ser Gly Gly Asp 520 Tyr Thr Asn Ser Phe 525 Wall Phe Asn Glu Gly 530 Ala Ser His Phe Lys 535 Wall Phe Phe Asn Tyr 540 Gly Gly Cys Phe

(2) Information for SEQ ID NO: 90:

(i) Sequence characteristics:

(A) Length: 356 amino acids (B) Type: amino acid (D) Topology: linear (ii) Molecule type: protein (iii) Hypothetical: YES (vi) Original source:

(A) Organism: Helicobacter pylori (ix)

(A) Name / Key: misc_charakter (B) Location: 1 ... 356 (xi) Description of Sequence: SEQ ID NO: 90:

Leu Met Lys Ser Ile Leu Phu Met Ile Phe Val Cys Gin Leu ^{1 5} 10 _ 15

Glu Lys Lys Lys Phe Ser Gin Asp Asn Phe LyS Val. Asp Tyr Asn Tyr

25 30 •

······· • · · «· · · Tyr Leu Arg Lys, Gin, Asp Leu His Ile Ile Lys Thr Gin Asn Asp Leu 35 40 45 Ser Asn Ala Trp Tyr Leu Pro Gin Lys Ala Pro Lys Glu His Ser 50 55 60 Trp Val Asp Phe Ala Lys Tyr Leu Asn Met Met Asp Tyr Leu Gly 65 70 75 80 Thr Tyr Phe Leu Phe Tyr His Ser Phe Thr Pro Ile Phe Gin B5 90 95 Tyr His Pro Asn Ile Asn For Tyr Gin Arg Asn Glu Phe Lys Phe Gin 100 105 110 Ile Phe Arg Val Pro Phe Arg His Ile. Leu Trp .Thr Lys Gly 115 120 : i25 Thr Leu Tyr Leu Ala Tyr Gin Thr Asn Trp Phe Gin Ile Tyr.Asn 13 0 135 140 -Asp — For Gin -Ses-Ala-Pro-MetArg-Met-I-le-Asn- -Phe-Met- Pro-Glu-Leu 145 150 155 160 Ile Tyr Val Lys Pro Phe Gly Gly Lys Ile Gly 165 170 175 Asn Phe Ser Glu Ile Trp His Ile Ser Asn Gly Val 180 185 190 Gly Gly Ala Gin cys tyr gin pro phe asn lys Glu Gly Asn Pro Glu 195 200 205 Asn Gin Phe For Gly Gin For Val Ile Val Lys. Asp Tyr Asn Gly Gin 210 215 220 Lys Asp Val Arg Trp Gly Cly Xaa Ser Val Xaa Xaa Gly Asn Xaa 225 230 · -235 240 Leu Cys Phe Val Leu Val Trp Leu Lys Ile Met Val 245 250 255 Ala Tyr Trp Pro Tyr Val Pro Tyr Asp Gin Ser Asn Pro Gin Leu Ile 260 265 270 Asp Tyr Met Gly Tyr Gly Asn & Ala Lys Ile Asp Tyr Arg Arg Gly Arg 275 280 285 His His Phe Glu Leu Tyr Asp Ile Phe Thr Gin Tyr Trp Arg 290 295 300 Tyr Asp Arg Trp His Gly Tyr Thr Tyr Arg Ile 305 310 315 320 Asn Pro Phe Val Gly Ile Tyr Ala Gin Php Asn Gly Tyr Gly Asp 325 330 335 Gly Leu Tyr Glu Tyr Asp Phe Ser Asn Arg Ile Gly Val Gly Ile 340 345 350 Arg Leu Asn For 355

(2) Information for SEQ ID NO: 91:

(i) Sequence characteristics:

(A) Length: 675 amino acids (B) Type: amino acid ·· · ·

917 Topology: linear (ii) Molecule type: protein (iii) Hypothetical: YES (vi) Original source:

(A) Organism: Helicobacter pylori (ix)

(A) Name / Key: misc_character (B) Location: 1 ... 675

(xi) Description sequence: SEQ ID NO: 91: Leu 1 Ser Lys Gly Leu 5 Ser Ile Gly Asn Lys 10 Ile Ile Leu Cys Wall 15 Dec Ala Leu Ile Wall Ile 20 May Wall Cys Wall Ser Ile 25 Leu Gly Wall Ser Leu 30 Asn Ser Arg Wall Lys 35 Glu Ile Leu Lys Glu 40 Ser Ala Leu His Ser 45 Met Gin Asp Ser Leu 50 His Phe Lys Wall Lys 55 Glu Wall Gin Ser Wall 60 Leu Glu Asn Thr Tyr 65 Thr Ser Met Gly Ile 70 Wall Lys Glu Met Leu 75 For Glu Asp - Thr Lys 80 Arg Glu Ile Lys Ile 85 Gin Leu Leu Lys Asn 90 Phe Ile Leu Ala Asn 95 Ser His Wall Ala Gly 100 ALIGN! Wall Ser Met Phe Phe 105 Lys Asp Arg Glu Asp 110 Leu Arg Leu Thr Leu 115 Leu Arg Asp Asn Asp 120 Thr Ile Lys Leu Met 125 Glu Asn For Ser Leu 130 Gly Ser Asn For Leu 135 Ala Gin Lys Ala Met 140 Lys Asn Lys Glu Ile 145 Ser Lys Ser Leu For 150 Tyr Tyr Arg Lys Met 155 For Asn Gly Ala Glu 160 Wall Tyr Gly Wall Asp 165 Ile Leu Leu For Leu 170 Phe Lys Glu Asn Thr 175 Gin Glu Wall Wall Gly 180 Wall Leu Met Ile Phe 185 Phe Ser Ile Asp Ser 190 Phe Ser Asn Glu Ile 195 Thr Lys Asn Arg Ser 200 Asp Leu Phe Leu Ile 205 Gly Wall Lys Gly Lys 210 Wall Leu Leu Ser Ala 215 Asn Lys Ser Leu Gin 220 Asp Lys Ser Ile Thr 225 Glu Ile Tyr Lys Ser 230 Wall For Lys Ala Thr 235 Asn Glu Wall Met Ala 240 Ile Leu Glu Asn Gly 245 Ser Lys Ala Thr Leu 250 Glu Tyr Leu Asp For 255 Phe Ser His Lys Glu 260 Asn Phe Leu Ala Wall 265 Glu Thr Phe Lys Met 270 Leu Gly Lys Thr Glu 275 Ser Lys Asp Asn Leu 280 Asn Trp Met Ile Ala 285 Leu Ile Ile Glu Lys 290 Asp Lys Wall Tyr Glxi 295 Gin Wall Gly Ser Wall 300 Arg Phe Wall Wall Wall 305 Ala Ala Ser Ala Ile 310 Met Wall Leu Ala Leu 315 Ile ,, .Ile Ala Ile Thr 320 Leu Leu Met Arg Ala 325 Ile Wall Ser Asn Arg 330 Leu Glu Wall Wall Ser 335 Ser

214

Thr Leu Ser His Phe Lys Leu Leu Asn Asn Gin Ala His Ser Ser 345 345 350

Asp Ile Lys Le Glu Ala Arg Ser Asn Asp Glu Le Glu Arg Met 355 360 365

Gin Thr Ala Ile Asn Lys Asn Ile Leu Gin Thr Gln Lys Thr Met Gin:

370 375 380

Glu-Asp Gin Ala Val Gin Asp Thr Ile Lys Val Ser-Asp Val

385 390 395 400

Lys Ala Gly Asn Phe

405 410 415

Asp Leu Lys Glu Leu

420 425 '. 430

Gin Glu Ser Gle Thr His Met Pro Ser Ile Phe Lys .Ile Phe Glu. 435 '440, 445' ·.

Ser Gly · Ser Gly Leu Asp Phe Arg

450 455 ⁴⁶⁰

Arg Val Glu Leu Val .Thr Asn Ala Leu Gly Gin Ilu Gin. Lys Met

465,470 '. 475 ------------ 480

Leu Glu Thr Ser Ser Asn Phe Ala Lys Asp

485 490 495

Asn Leu Lys Glu Cys 500 Val Gin Asn Leu Glu Lys Ala Ser 505 510 His Lys Ser Leu Met Glu Thr Ser ^- Lys Thr ile 'Glu Asn Ile Thr Thr 515 520 525 Ser ' Ile- Gin Gly Wall Ser Ser Gin Ser Glu Ala Met Ile Glu Gin Gly 530 535 540 Lys Asp Ile Lys Ser Ile Wall Glu ,. Ile Ile Arg Asp Ile Ala Asp Gin 545 550 555 560 Thr Asn Leu Leu Ala Leu Asn Ala Ala Ile • Glu Ala Ala Arg Ala Gly 565 570 575 Glu His Gly Arg Gly Phe Ala Wall Wall Ala Asp Glu Wall Arg Lys Leu 580 585 590 Ala Glu Arg Thr Gin Lys Ser Leu Ser Glu Ile Glu Ala Asn Ile Asn 595 600 605 Ile Leu Wall Gin Ser Ile Ser Asp Thr Ser Glu Ser Ile Lys Asn Gin 610 615 620 Wall Lys Glu Wall Glu Glu Ile Asn Ala Ser Ile Glu Ala Leu Arg Ser 625 630 635 640 Wall Thr Glu Gly Asn Leu Lys Ile Ala Ser Asp Ser Leu Glu Ile Ser 645 650 655 Gin Glu Ile Asp Lys Wall Ser Asn Asp Ile Leu Glu Asp Wall Asn Lys 660 665 670 Lys Gin Phe 675

(2) Information for SEQ ID NO: 92:

(i) Sequence characteristics:

(A) Length: 271 amino acids (B) Type: amino acid (D) Topology: linear

215 (ii) Type of molecule: protein (iii) Hypothetical: YES (vi) Original source ·:

- (A) Organism: Helicobacter pylori (ix)

(A) Name / Key: misc_charakter (B) Location: 1 ... 271 (xi) Sequence Description: SEQ ID'NO: 92:

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

(2) Information for SEQ ID NO: 9-3:

216

0 (i) Sequence characteristics:

(A) Length: 161 amino acids, (B) Type: amino acid (D) Topology: linear (ii) Molecule type: protein (iii) Hypothetical: YES (vi) Original source:

(A) Organism: Helicobacter pylori

- (ix) VI as tno sti: —----------------------- (A) Name / Key: misc_charakter (B) Location: 1 ... 161

Met Phe (xi) Description Phe Lys Thr i sequence: Tyr Gin Lys SEQ Leu ID Leu NO: Gly 93 Ala Ser Cys Leu Ala 1 Leu Tyr Leu Wall 5 Gly Cys Gly Asn Gly 10 Gly Gly Gly Glu Ser 15 Dec For Wall Glu Met Ile 20 May Ala Asn Ser Glu Gly 25 Thr Phe Gin Ile Asp 30 Ser Lys Ala Asp Ser 35 Ile Thr Ile Gin Gly 40 Wall Lys Leu Asn Arg 45 \ Gly Asn Cys Ala Wall 50 Asn Phe Wall For Wall 55 Ser Glu Thr Phe Gin 60 Met Gly Wall Leu Ser 65 Gin Wall Thr For Ile 70 Ser Ile Gin Asp Phe 75 Lys Asp Met Ala Ser 80 Thr Tyr Lys Ile Phe 85 Asp Gin Lys Lys Gly 90 Leu Ala Asn Ile Ala 95 Asn Lys Ile Ser Gin 100 ALIGN! Leu Glu Gin Lys Gly 105 Wall Met Met Glu For 110 Gin Thr Leu Asn Phe 115 Gly Glu Ser Leu Lys 120 Gly Ile Ser Gin Gly 125 Cys Asn Ile Ile Glu 130 Ala Glu Ile Gin Thr 135 Asp Lys Gly Ala Trp 140 Thr Phe Asn Phe Asp

145 150 155 160 Lys (2) Information for SEQ ID NO: 94:

(i) Sequence characteristics:

(A) Length: 337 amino acids (B) Type: amino acid (D) Topology: linear (ii) Molecule type: protein (iii) Hypothetical: YES

217 (vi) Original source:

(A) Organism: Helicobacter pylori (ix) Properties:

(A) Name / Key: misc_charakter (B). Location: 1 ... 337 (xi) Description of sequence: SEQ ID NO: 94:

Met Ile Arg Lys Gly Leu Asn Lys Thr Leu Lys Thr.Ser Leu Leu 1 5 10 15 Dec Ala Gly Val Leu Leu Gly Ala Thr Ala Met Ala Lys For Leu Leu Ser Asp 35 Glu Asp Leu Leu Lys Arg Val Lys Leu His Asn Ile Lys Glu Asp 50 Thr Leu Thr Cys Asn Ala Lys Val 55 Asp Gly Ser 60 Gin Tyr Leu > 65 Asn Ser Gly Trp Asn Leu Ser Lys Glu Phe 76 For Gin Glu Tyr Arg 80 Glu Lys Ile Phe Glu Cys Val Glu Glu Glu Lys His Lys Gin Ala 95 Leu Asn Leu Ile Asn Lys Glu Asp Thr Glu Glu Glu Leu 110 Ala Lys Lys Ile Lys 115 Glu Ile Lys Glu Lys Ala Lys Val Leu Arg Gin 125 Lys Phe Met Ala 130 Phe Glu Met Lys Glu His Ser Lys Glu. 135 Phe Pro Asn Lys Lys Gin 145 Leu Gin Thr Met Leu 150 Glu Asn Ala Phe Asp 155 Asn Gly Ala Glu Ser 160 Phe Ile Asp Asp Trp His Glu Arg Phe Gly Gly Ile Ser Arg Glu 175 Asn Thr Tyr Lys Ala Leu Gly Ile Lys Glu Tyr Ser 185 Asp Glu Gly Lys Ile Leu Ala Phe 195 Gly Glu Arg Ser Tyr Ile Arg Gin Tyr Lys Lys Asp Phe Glu Glu 210 Ser Thr Tyr Asp Thr Arg Gin Thr Leu Ser Ala Met 220 Ala Asn Met 225 Ser Gly Glu Asn Asp 230 Tyr Lys Ile Thr Trp 234 Leu Lys Pro Lys Tyr 240 Gin Leu His Ser Ser Asn 245 Asn Ile Lys Pro Leu 250 Met Ser Asn Thr 255 Glu Leu Leu Asn Met Ile Glu 260 Leu Thr Asn Ile Lys 265 Lys Glu Tyr 270 Wall Met Gly Cys Asn 275 Met Glu Ile Asp Gly Ser Lys Tyr 280 For Ile His 285 Lys Asp Trp Gly 290 Phe Phe Gly Lys Ala Lys Val Pro Glu 295 Thr Trp Arg 300 Asn Lys Ile 305 Trp Glu Cys Ile Lys Asn Lys Val Lys Ser 315 Tyr Asp Asn Thr Thr 320 Ala Glu Ile Gly Ile Val 325 Trp Lys Lys Asn Thr ~ 330 Tyr Ser Ile Ser 335 His

218 (1). Information for SEQ ID NO: 95:.

(ij Sequence characteristics:

(A) Length: 416 amino acids (B) Type: amino acid (D) Topology :, linear (ii) * Molecule type: protein (iii) Hypothetical: YES (vi) Original source:

--- (A) —Organism -: - Helicobacter — pylori -------- (ix)

(A) Name / Key: misc_charakter (B) Location: 1 ... 416

(xi) Sequence description: SEQ ID NO: 95: Met Lys Lys Le Phu Ser Met Leu Leu Cys Cys Lys Sher Val Phe 1 5 10 15 Dec Ala Glu Gly Glu Thr For Leu Ile Val Asn Asp Pro Glu Thr His Val 20 May 25 30 Ser Gin Ala Thr Met Val Asp Ser Ile Lys Arg Tyr 35 40 45 Glu Glu Ile Ile Ala Gin Val Gn Leu Gin Lys 50 55 60 Wall Asn Asn Thr Thr Asn Ser Leu Ile Ser Ser Ser Ala 65 70 75 80 Ile Thr Leu Ala Asn For Met Gin Val Leu Gin Asn Ala Gin 85 90 95 Ile Glu Ser Ile Arg Tyr Asn Tyr Glu Asn Leu Lys Gin 100 ALIGN! 105 110 Asn Asp Ala Gin Asn Leu Leu Arg Asn Lys Tyr Lein Gin Gin Gin 115 120 125 Cys For Trp Leu Asn Val Asn Ala Leu Thr Asn Lys Ile Val Asn 130 135 140 Leu Lys Asp Leu Asn Asn Leu Ile Thr Lys Asn Gly Glu 145 ¹⁵⁰ 155 160 Thr Ala Arg Asp Gin Asn Leu Ile Gin Ser Gly Ser Gly 165 170 175 Tyr Gly Asn Met Gly Glu Leu Ser Gly Arg Ala Trp 180 185 190 Gly Glu Met Leu Asn Asp Ser Asn Tyr Glu 195 200 205 Gin Ala Ler Leu Ala Thr Gly Asn Asn Pro Glu Glu Lys Arg Arg 210 215 220 Phe Leu Leu Arg Lys Lys Lys Val Asn Asp Asn Lys. Gin Leu Lys 225 230 235 240 Asp Lys Leu Asp For Phe Leu Lys Arg Leu Asp Val Leu Gin Thr Glu 245 250 255 Phe Gly Val Thr Asp Asn His Asn Lys Gin Ily His 260 265 270 Tyr Cys Thr Glu Lys Cys Asp For Ile Lys Asn 275 280 285 Wall, Phe Arg Thr Thr Arg Leu Glu I Glu Glu 290 295 300 Thr Leu Thr Leu Ile Lys Ala Ser Asn Lys Asp. Ala Gin Ser 3 05 310 315 320

0 · 00 · 00 ·

0 0 0 0 0 0 0

000 000 0 0

00

Gin Ala Tyr Ala Asn 325 Phe Asn Gin Arg Ile 330 Lys Leu Leu Thr Leu 335 Lys Tyr Leu. Lys Glu 340 Ile Thr Asn Gin Met 345 Leu Phe Leu Asn Gin 350 Thr Met Ala Met Gin 3S5 Ser Glu Ile Met Thr 360 Asp Asp Tyr Phe Arg 365 Gin Asn Asn Asp Gly 370 Phe Gly Glu Lys Glu 375 Asn His Ile Asp Lys 380 Gin Leu Thr Gin Lys 385 Arg . He Asn Glu Arg 390 Glu Arg Ala Arg Ile 395 Tyr Phe Gin Asn For 400 Asn Wall Lys Phe Asp 405 Gin . Phe Gly Phe For 410 Ile Phe Ser Ile Trp 415 Asp

(2) Information for SEQ ID NO: 96:

- (- i -) - Sequence characteristics: _____________ (A) Length: 376 amino acids (B) Type: amino acid (D) Topology: linear (ii) Molecule type: protein (iii) Hypothetical: YES (vi) Original source :

(A) Organism: Helicobacter pylori (ix)

(A) Name / Key: misc_charakter (B) Location: 1 ... 376

(xi) Sequence description: SEQ ID NO: 96: Wall 1 Asn Lys Gly Ala Val 5 Wall 10 Phe Val Gly Phly Ala 15 Thr Ile Thr Thr Phe Ser Leu His Gin Lys Pro Leu Asn Gn Pro Ser Leu Leu Asn 35 40 Asp Asp Glu Val Lys Tyr Pro Leu Gin Asp Tyr Thr Phe Thr For Gin Pro Thr Asn Thr Glu Ser 65 Ser Lys Asp Ala Thr Leu Gin Glu Gin Leu Lys Ala 75 Ala Leu Lys Ala Leu Asn Ser Lys Glu Met 90 Asn Tyr Ser Lys Glu Glu Thr Phe Thr Pro Pro Met Asp Pro 100 105 Lys Thr Thr Pro Lys Lys 110 Asp Phe Ser Pro Lys Asp Leu 115 120 Leu Ala Ser Arg Ile Thr Pro 128 Phe Lys Gin Ser Lys Asn Tyr Glu 130 135 Glu Asn Leu Ile Phe Pro Val Asp 145 Asn Pro Asn Gly Ile Thr Asn Leu Lys Glu Lys Asp 155 Ile Ala Thr Asn Glu Asn Lys Leu Leu Arg 170 Thr Ile Thr Ala Asp Lys Met Ile Pro Ala Phe Leu Ile Ser Gin Ile Ala Gly 190. Lys Val Ile Ala Gin Ile Phe Ala Ser Met (Original Mix) Gly Lys 205 Ala Val Leu Ile Lys Gly Ser Lys 210 215 Wall Ile Gly Tyr Tyr Ser Asn 220

· · Ii ii · ii ii ii ii ii

Asn Lys Met Gly Tyr Arg

225 230

Ile Thr For His Gly Ile

245

Asp Ile Lys Gly 260 Tyr Asn Gly Leu 4? Phe Gin Arg Tyr Gly Val Pro Leu 275 280 Leu Leu Ile Gly Ile Thr Ser Ala. : 290 . 295 Glu Val Thr Asn Gly Asp 'Phe Phe 305 310 Gla Ser Gly Mec Gly Ile Asn Gin ' -. 325 Lys. Ser Lys Ile Ala Pro, · Ile Val ¹ 340 Phe Ile. Ser For Asn Thr Asp Ile 355 360 Glu Val Ile .Ala- Glu-Phe-Leu Lys 370 375

··· ···· ·· Φ ·· ··

Leu Asp Ile Val Trp Ser Ile 235 240

Met Leu Thr Asn Ala Lys Gly Ala 250

Glu Glu Leu Ile Glu Arg Asn

2S5 270

Leu Leu Ser .Thr Leu Thr Asn Gly 285 Leu Asn Asn Arg Gly Asn Lys Glu 300 Tyr Leu Leu Leu Gin Leu Met Arg , 315 · 320 Wall Wall Asn .Gin .Ile Leu · Arg Asp 330 335 Wall Ile Arg .Glu ..Gly Ser, Arg Wall 345 350 Phe Phe For Ile For Arg Glu Asn 365

(2) Information for SEQ ID NO: 97:

(i) Sequence characteristics:. (A) Length: 916 amino acids ^; (B) Type: amino acid (D) Topology: linear (ii) Molecule type: protein (iii) Hypothetical: YES (vi) Original source:

(A) Organism: Helicobacter pylori (ix)

(A) Name / Key: misc_charakter (B) Location: 1 ... 916 (xi) Description of Sequence: SEQ ID NO: 97:

Wall Asp Leu Arg Ile Gin Ser Lys Glu Wall Ser His Asn Leu Lys Glu 1 5 10 15 Dec Leu Ser Lys Thr Leu Ile Ser Tyr For Phe Glu Lys His Wall Glu Ala 20 May 25 30 Leu Gly Glu Gin Cys Ser Asn Phe Wall Ser Ile For Ile Asn Asn Asp 35 40 45 Asp. Tyr Ser Asn Ile Cys Thr Phe Wall Ser Asp Phe Ile Ásn Leu Ile 50 55 ⁶⁰ Ala Ser Tyr Asn Leu, Leu Glu Ser Phe Leu Asp Phe Tyr Lys Asp Lys 65 70 75 ⁸⁰ Leu Lys Leu Ser Glu Leu Wall' .Thr Glu Tyr Ala Asn wall Thr Asn Asn 85 90 95 • Leu Leu Phe Lys Lys Leu Ilé \ • i, i Lys His Leu Ser Gly Asn Asn Gin Leu 100 ALIGN! 105 110

····

• '4 · • • • 9 • • « • 9 9 9 '· • • 221 • * 9 • 9 · 9 9 • • • · « 9 99 9 • « ··· ···· ·· • · « 99 Wall Lys Asn Phe Tyr Gin Cys Ile Arg Glu Ile Ile Lys Tyr Asn Ala 115 120 125 For Asn Lys Glu Tyr Lys For Asn Gin Phe Phe Ile Ile Gly Lys Gly 130 135 140 Lys Gin Lys Gin Leu Ala Lys Ile Tyr Ser His Leu Lys Glu Leu Ser 145 ISO 155 160

Ala Ser Glu Ile Lys 165 For Gin Asp Met Glu 170 Asp Ile Leu Lys Lys 175 Leu Glu Glu Leu Asp 180 Lys Ile Phe Lys Thr 185 Thr Asp Phe Thr Lys 190 Phe Thr For Lys Thr 195 Glu Ile Lys Asp Ile 200 Ile Lys Glu Ile Asp 205 Glu Lys Tyr For Ile 210 Asn Glu Asn Phe Lys 215 Arg Gin Phe Asn Glu 220 Phe. Glu Ser Asn Ile 225 Glu Lys His Asp Glu 230 Ile Lys Lys Asp Phe 235 Glu Arg Asn Lys Glu 240 Ser Leu Ile Arg Glu 245 Ile Glu Asn His Cys 250 Lys Asn Glu Cys Asn 255 Ser Glu Glu Glu For_ 260 Lu Glu. -Tyr- Lys -Tle- Asn Asp 265 Leu Leu Lys Asn 270 Ile Gin Gin Ile Cys 275 Lys Asn Tyr Ile Glu 280 Ser His Ala Wall Asn 285 Asp Wall Ser Lys Asp 290 Ile Lys Ser Met Met 295 Cys Gin Phe Tyr Leu 300 Lys Gin Ile Asp Leu , 305 Leu Wall Asn Ser Glu 310 Ile Wall Arg Tyr Arg 315 Tyr Ser Asn Leu Phe 320 Glu For Ile Gin Arg 325 Ser Leu Trp Glu Ser 330 Ile Lys Ile Leu Asp 335 Asn Glu Ser Gly Ile 340 Tyr Leu Phe For Lys 345 Asn Ile Gly Glu Ile 350 Lys Asp Lys Phe Glu 355 Ala Asn Lys Glu. Lys 360 Phe Lys Gin Ser Lys 365 Asn Wall Ser Glu Phe 370 Ala Glu Tyr Cys Arg 375 Glu Cys Asn For Tyr 380 Thr Ala Phe Asn Phe 385 His Leu Asn Ile Asn 390 Asn Gly Leu Ser His 395 Gin Phe Glu Lys Phe 400 Wall For Ile Met Lys 405 Glu Tyr Lys Glu For 410 Lys Ile Thr Asp Asn 415 Asp Leu Glu Ala Ile 420 Ser Thr Lys Glu Thr 425 Gly Leu Ala Ser Gin 430 Leu Ser Gly His Trp 435 Phe Phe Gin Leu Ser 440 Leu Phe Asn Lys Thr 445 Asn Phe Asn For Asn 450 Lys Ile Trp Ile For 455 Leu Glu Phe Asn Lys 460 Arg Ser Lys Ile Lys 465 Phe Asp Lys Asp Leu 470 Glu Ile Tyr Phe Asp 475 Ser His Glu Ser Phe 480 Asn Ile Ser Lys Lys 485 Tyr Leu Gin Glu Ile 490 Asp Gin Glu Ser Leu 495 Lys Lys Ile Lys Gin 500 Ser Lys Asp Phe Phe 505 Ser Ile Gin Lys Ile 510 Glu Ser Lys His Asp 515 Asn Asn Asp Ile Leu 520 Gin Leu Glu Phe Phe 525 Glu Asn Asp Thr Ser 530 Phe Leu Phe Ala Lys 535 Gly Ser Phe Ala Glu 540 Ile Leu Glu Tyr Asn 545 Met Gin Leu Lys Ile 550 Asp Ser Leu Ile Thr 555 Lys Glu Phe Ásn Lys 560 Leu Leu Ala Ile Wall 565 Gin Asp Ser For Gin 570 Asp Ser Tyr Gin Leu 575 Lys Ile Arg wall Arg 580 His Asn Asn Lys Leu 585 For Arg Glu. Lys Tyr 590 Thr Glu; His Glu Ile Lys Leu Glu Wall Tyr Asp Cys Arg Lys Ser His Asp His i

»· ·· ·····

······· • · • • · ' 595 600 605 Asn Glu Pro Ile Ile Leu Ser Gin Gin Ser Thr Gly Phe Gin Trp Ala 610 615 620 Phe Asn Phe Met Phe Gly Phe Leu Tyr Asn Wall Gly Ser His Phe Ser S25 630 635 640 Phe Asn His Asn Ile Ile Tyr Wall Met Asp Glu For Ala Thr His Leu 645 650 655 Ser Wall Pro Ala Arg Lys Glu Phe Arg Lys Phe Leu Lys Glu 'Tyr Ala .660 665 670 His Lys Asn His Wall Thr Phe Wall Leu Ala Thr His ¹ Asp For Phe Leu 675 680 ¹ 685 Wall Asp Thr Asp His Leu Asp- Glu Ile Arg Ile Wall Glu Lys. Glu Thr 690 ' 695 700 Glu Gly Ser 'Val Ile Lys Asn His Phe Asn Tyr For Leu ' Asn Asn Ala 705 710 715 720 Ser Lys Asp-Ser Asp Ala -Leu Asp Lys Ile Lys Arg Ser Leu Gly Wall His Val 725 730 735 Gly Gin Phe His Asn For Gin Lys His Arg Ile Ile Phe Wall 740 745 750 Glu Gly Ile Thr Asp Tyr Cys Tyr Leu Ser Ala Phe Lys Leu Tyr Leu 755 760 765 Arg Tyr Lys Glu Tyr Lys Asp Asn For Ile For Phe Thr Phe Leu For 770 775 780 Ile Ser Gly Leu Lys Asn Asp Ser Asn Asp Met Lys Glu Thr Ile Glu 785 790 795 800 Lys Leu Cys Glu Leu Asp Asn His For Ile Wall Leu Thr Asp Asp Asp 805 810 815 Arg Lys Cys Val Phe Asn Gin Gin Ala Thr Ser Glu Arg Phe Lys Arg 820 825 830 Ala Asn Glu Glu Met His Asp For Ile Thr Ile Leu Gin Leu Ser Asp 835 840 845 Cys Asp Arg His Phe Lys Gin Ile Glu Asp Cys Phe Ser Ala Asn Asp 850 855 860 Arg Asn Lys Tyr Ala Lys Asn Lys Gin Met Glu Leu Ser Met Ala Phe 865 870 875 880 Lys Thr Arg Leu Leu Tyr Gly Gly Glu Asp Ala Ile Glu Lys Gin Thr 885 890 895 Lys Arg Asn Phe Leu Lys Leu Phe Lys Trp Ile Ala Trp Ala Thr Asn 900 905 910 Leu Ile Lys Asn

915

223 • ·· 0 \ 0 00 '0 0 ‘0' 0 · '0 0 • 0 000 0000' 0 '0 .0' · • 0 <· '0 0 (2) Information for SEQ ID NO: 98:

(i) Sequence characteristics:

(A) Length: 176 amino acids (B) Type: amino acid .. (D) Topology: linear (ii) Molecule type: protein (iii) Hypothetical: YES (vi) Original source:

_____ 4A) _Organism: He-iicobacter pylori (ix)

(A) Name / Key: misc_charakter (B) Location: 1 ... 176

Met (Xi) ’Thr Ala Sequence Description Met Met Arg Tyr SEQ ID Phe His NO Ile : 98 Tyr Ala Thr Thr Phe Phe 1 Phe For Leu Ala 5 Leu Leu Phe Ala Wall. 10 Ser Gly Leu Ser Leu 15 Dec Leu Phe Lys Ala Arg 20 May Gin Asp Thr Gly Ala 25 Lys Ile Lys Glu Trp 30 Wall Leu -Glu Lys Ser 35 Leu Lys Lys Glu Glu 40 Arg Leu Asp Phe Leu 45 Lys Gly Phe Ile Lys 50 Glu Asn His Ile Ala 55 Met For Lys Lys Ile 60 Glu For- Arg Glu Tyr 65 Arg Gly Ala Leu Wall 70 Ile Gly Thr For Leu 75 Tyr Glu Ile Asn Leu 80 Glu Thr Lys Gly Thr 85 Gin Thr Lys Ile Lys 90 Thr Ile Glu Arg Gly 95 Phe Leu Gly Ala Leu 100 ALIGN! Ile Met Leu His Lys 105 Ala Lys Wall Gly Ile 110 Wall Phe Gin Ala Leu 115 Leu Gly Ile Phe Cys 120 Wall Phe Leu Leu Leu 125 Phe Tyr Leu Ser Ala 130 Phe Leu Met Wall Ala 135 Phe Lys Asp Thr Lys 140 · Arg Met Phe Ile Ser 145 · Wall Leu Ile Gly Ser 150 Wall Wall Phe Phe Gly 155 Ala Ile Tyr Trp Ser 160 Leu (2) 165 Information for SEQ ID NO: 170 yy: 175

(i) Sequence characteristics:

(A) Length: 222 amino acids (B) Type: amino acid (D) Topology: linear (ii) Molecule type: protein

(Iii) Hypothetical: YES (vi) Original Source:

(A) Organism: Helicobacter pylori (ix) Features :.

(A) Name / Key: misc_charakter (B) Location: 1 ... 222 (xi) Sequence Description: SEQ ID NO: 99:

Met Phe Lys Asn Ile Gin Asp Phe Lys Asn His

10 ____________________15___

Thr Ser Thr Ala Ile Ily Gly Thr Asn Gly Ala Gly Lys Ser Thr Leu

25 30

Ile Asn Thr. Ile Leu Gly

35 40 45 Asn Asn Asn Ile For Tyr His Asp Asn Wall Ile For Gin Arg Lys Gin 50 55 60 .‘Leu Gly Wall Wall Ser Asn Leu Phe Asn Tyr For For Gly Leu Asn Ala 65 70 75 80 Asn Asp Leu Phe Lys Phe Tyr Gin Phe Phe His Lys Asn Cys Thr Leu 85 90 95 Asp Leu Phe Glu Lys Asn Leu Leu Asn Lys .Thr Tyr Glu His Leu Ser 100 ALIGN! 105 110 Asp Gly Gin Lys Gin Arg Leu Lys Ile Asp Leu Ala Leu Ser His His 115 120 125 For Gin Leu Wall Ile Met Asp Glu For Glu Thr Ser Leu Glu Gin Asn 130 135 140 Ala Leu Ile Arg Leu Ser Asn Leu Ile Ser Leu Arg Asn Thr Gin Gin 145 150 155 160 Leu Thr Ser Ile Ile Ala Thr His Asp For Ile Wall Leu Asp Ser Cys 165 170 175 Glu Trp Wall Leu Leu Leu Lys Asn Gly Asn Ile Ala Gin Tyr Lys For 180 185 190 Leu Asn Ser Ile Leu Lys Ser Wall Ala Lys Thr Phe Asn Phe Lys Glu 195 200 205 Lys For Thr Thr Lys Asp Leu Leu Ala Leu Leu Lys Asp Ile 210 215 220

(2) Information for SEQ ID NO: 100:

(i) Sequence characteristics:

(A) Length: 406 amino acids (B) Type: amino acid (D) Topology: linear (ii) Molecule type: protein (iii) Hypothetical: YES (• j '·; «

225 · · · ·

(vi) Original source:

(A) Organism: Helicobacter pylori (ix)

(A) Name / Key: misc_character (B) Location: 1 ... 406 (xi) Sequence Description: SEQ ID NO: 100:

Met Tyr Ala Ala His Pro Ile Lys Pro Ile Lys Ala Pro Lys Leu Lys 1 5 10 13 Ser Gln. Phe Leu Arg Arg GlyAla Ser Ile Arg Arg -T-rp— Asn Asp Gin Ala Cys Pro Glu Phu 40 Wall Glu Leu Asp Lys Gin Ala His Lys 50 Ala Met Ile Ala Tyr Leu Leu Ala Lys Asp Leu Lys Asp Arg Gly Lys Asp Leu Asp Leu Leu Ile Lys 75 Tyr Phe Cys Phe Glu 80 Phe Leu Glu Arg Leu Val 85 Leu Thr Asp Ile 90 Lys Pro Pro Ile Phe 95 Tyr Ala Leu Gin Gin Thr His 100 ALIGN! Ser Lys Glu Leu Ala Ser Tyr Val Ala, Gin Ser Leu Gin Asp Glu Ile 114 Ser Ala Tyr Phe Ser Leu Glu 125 Leu Lys Glu Tyr 130 Leu Ser His Arg For Gin Ile 135 Leu Glu Thr Gin Ile Leu Glu Ser 145 Ala His Phe Tyr Ala 150 Ser Lys Trp Glu Phe 155 Asp Ile Ile Tyr His 160 Phe Asn For Asn Me Tyr 165 Gly Val Lys Glu 170 Ile Lys Asp Lys Ile 175 Asp Lys Gin Leu His Asn Asn 180 Asp His Leu Phe Glu Gly Leu Phe 190 Gly Glu Lys Glu Asp Leu Lys Lys 195 Leu Val Ser 200 Met Phe Gly Gin Leu Arg Phe Gin Lys 210 Arg Trp Thr Pro Arg 215 Wall For Gin Thr Ser 220 Wall Leu Gly 225 His Thr Leu-Cys Val 230 Ala Ile Met Gly Tyr 235 Leu Leu Ser Phe Asp 240 Leu Lys Ala Cys Lys Ser 245 Met Arg Ile Asn 250 His Phe Leu Gly Gly 255 Leu Phe His Asp Leu Pro Glu 260 Ile Leu Thr 265 Arg Asp Ile Ile Thr 270 For Ile Lys Gin Ser Val Ala Gly Leu-Asp His 280 Cys Ile Lys Glu Ile 285 Glu Lys Lys Glu 290 Met Gin Asn Lys Val Tyr Ser 295 Phe Wall Twilight Gly 300 Wall Gin Glu 305 Asp Leu Lys Tyr Phe 310 Thr Glu Asn Glu Phe 315 Lys Asn Arg Tyr Lys 320 Asp Lys Ser His Gin Ile 325 Val Phe Thr Lys Asp 330 Ala.Glu Glu Leu 335 Phe Thr Leu Tyr Asn Ser Asp 340 Glu Tyr Leu ³⁴⁵ Gly Val Cys Gly Glu 350 Leu Leu Lys Wall Cys Asp His Leu 355 Ser Ala Phe 360 Leu Glu. Ala Gin Ile 365 ' Ser Leu.

226 (« • • · ·· ·· in· • · ·· • · • · • · · '· 9 9 9 9 • • · « • 9 • 9 9 · (· • • · Ser His Gly Ile Ser Ser Tyr Asp Leu Ile Gin Gly Ala Lys Asn Leu 370 375 380 Leu Glu Leu Arg Ser Gin Thr Glu Leu Leu Asp Leu Asp Leu Gly Lys 385 390 395 400 Leu Phe Arg Asp Phe Lys

405 (2) Information for SEQ ID NO: 101:

(i) Sequence characteristics:

(A) Length: 335 amino acids (B) Type: amino acid (D). Topology: linear (ii) Molecule type: protein (iii) Hypothetical: YES (vi) Original source:

(A) —Organism-; Helicobacter pylori (ix)

(A) Name / Key: misc_character (B) Location: 1 ... 335

(xi) Description sequence: SEQ ID NO: 101: Wall 1 Leu Trp Val Leu Tyr Phe Leu 4 Thr Ser 10 Leu Phe Ile Cys Ser Leu Ile Val Leu Trp Ser Lys Met 25 Leu Phe Val Asp Asn Ala Asn Lys Ile Gin Gly Kis Ala 40 Arg Thr For Arg Ala Gly Gly Leu 45 Gly Ile Phe Leu 50 Ser Phe Ala 55 Ala Cys Tyr Leu Glu Pro Phe Glu Met 55 For Phe Lys Gly Pro Phe Val Phe Leu Gly Leu Ser Leu Val Phe 75 Leu Ser Gly Phe Leu Glu Asp Ile-Asn Leu 90 Ser Lys Ser Pro Lys Ile 95 Arg Leu Ile Leu Gin Ala Val Gly Wall 105 Wall Cys Ile Ile Ser Ser Thr 110 For Val Val 115 Ser Asp Phe Ser 120 For Leu Phe Ser Leu Pro Tyr Phe 125 Ile Ala Phe Leu 130 Phe 135 Met Leu Val Gly Ile Ser Asn Ala Ile 145 Asn Ile Ile Asp Gly Phe Asn 150 Gly Leu Ala Ser Gly Ile Cys Ala Ile Ala Leu Leu Val Ile His Tyr Ile Asp 170 Pro Ser Ser Leu Ser Cys 175 Leu Leu Ala Tyr Met Val Leu Gly Phe 185 Met Val Leu Asn Phe Pro Ser 190 Gly Lys Ile Phe 195 Leu Gly Asp Gly 200 Gly Ala Tyr Phe Leu Gly Leu Val Cys Gly Ile Ser 210 Leu Leu His Leu 215 Ser Leu Glu Gin Lys Ile Ser Val Phe 225 Phe Gly Leu Asn Leu Met Leu 230 Tyr For Val Ile Glu Val Leu Phe 235 240 Ser Ile Leu Arg Arg Lys Ile Lys 245 Arg Gin 250 Lys Ala Thr Met For Asp 255 Asn Leu His Leu 260 His Thr Leu Leu Phe 265 Lys Phe Leu Gin Arg Ser 270 Phe. Asn Tyr Pro 275 Asn Pro Leu Cys 280 Ala Phe Ile Leu Ile Leu द्वारा किया Cys Asn 285 Ile Leu

227: · · ·

'· ’·· ···· * ·

Leu Phe Ile Leu Ile Ser Leu Phe Arg Leu Asp 290? 95 300

Leu Ile Val Ile Ser Phu Ile Ala Cys Tyr Leu

305 310 315

Ala Tyr Leu Gn Val Cys Ala, Leu Glu Lys Arg

325 330 (2) Information for SEQ ID NO: 102:

(i) Sequence characteristics:

(A) Length: 96 amino acids (B) Type: amino acid '´ (D) Topology: linear (ii) Molecule type: protein (iii) Hypothetical: YES (vi) Original source:

----------- (A) Organism: Helicobacter pylori

Aía Tyr * Aía ·· ’

Ile Gly Tyr 320

Ala Phe • 335 (ix) Features:

(A) Name / Key: misc_charakter (B) Location: 1 ... 96 (xi) Sequence Description: SEQ ID NO: 102:

Met

Leu

His

Asn

Ser

Ser (2)

Lys Lys Val Ile Val Ala Leu Gly Val Leu Ala Phe- Ala Asn Val 5 10 15 Dec Met Ala Thr Asp Val Lys Ala Leu Gly Cys-Ala Ala Cys 20 May 25 30 Gly val Lys Phe Glu Lys Lys Ala Ley Gly Lys Ser Lys Ile Val 35 40 45 Met Met Ser Glu Lys Glu Ile Glu Asp Leu Met Ala Phe Lys 50 55 60 Gly Ala Asn Lys Asn Pro Val Met Thr. Ala Gin Ala Lys Lys Leu 70 75 80 Asp Glu Asp Ile Lys Ala Lys Ala Lys Tyr Ile Pro Thr Leu Lys 85 90 95 Information for SEQ ID NO: 103:

(i) Sequence characteristics:

(A) Length: 156 amino acids (B) Type: amino acid (D) Topology: linear (ii) Molecule type: protein (iii) Hypothetical: YES (vi) Original source:

(A) Organism: Helicobacter pylori (ix)

(A) Name / Key: misc_charakter (B) Location: 1 ... 156

228 ···· • * · · · · «• · · · • ♦ · · · · · • ♦ • ····« · ₄

(xi) -Description SEQ ID NO: 103: Met Arg. Asp Phe Asn Asn Ile Gin Ile Thr Arg Leu 'Lys Val'Arg Gin 1 5 '10 15 Dec Asn Ala Val Phe Glu Lys Leu Phe Lys Asp Gly. Leu Ser 20 May 25 30 Ala Ile Ser Gly Ala '. Ser Gly. Val Gly Lys Ser Val Leu lie Ala Ser 35 • 40 45 Leu Gly Ala Leu. Phe Gly Leu Asn Ala Ser. Asn Ile Glu 50 55 60

Val Glu Leu Ile Ala Phe Leu Asp Thr Glu Glu Tyr Gly Ile Phe 65 · 70 _75__________ 80

Arg Glu Asp Glu His Glu Pro-Leu Val Ile Ser Wall Ile Lys Lys Glu 85., 90 Lys Thr Arg Tyr Phe Leu Asn Gin Thr Ser Leu Ser Lys Asn Thr Leu 100 ALIGN! 105 110 Lys Ala Leu Leu Lys Gly Leu Ile Lys Arg Leu Ser Asn Asp Arg Phe 115 120 125 Ser Gin Asn Glu Leu Asn Asp Ile Leu Met Leu Ser Leu Leu Asp Gly 130 135 140 Tyr Ile Gin Asn Lys Asn Arg Arg Leu Ala For Phe 145 150 155

(2) Information for SEQ ID NO: 104:

(i) Sequence characteristics:

(A) Length: 118 amino acids (B) Type: amino acid (D) Topology: linear (ii) Molecule type: protein (iii) Hypothetical: YES (vi) Original source:

(A) Organism: Helicobacter pylori (ix)

(A) Name / Key: misc_charakter (B) Location: 1 ... 118 (xi) Sequence Description: SEQ ID NO: 104:

Wall Met Leu Met Ala Ile Phe Thr For Tyr Ile Leu Ile Leu Lys Met 1 5 · 10 15 Dec Met Lys Lys Ser Met Ser Leu Phe Ala Asn Met Gly Leu Glu Gin Ile 20 May 25 30 Phe Cys Asn Arg Asp Ile Lys Asp Leu Asn Asp Phe Wall Phe Gly Ile 35 40 45 Glu Wall Gly Leu ¹ Asp Ser Asn Ala Arg Lys Asn Arg Ser Arg Lys Ala 50  . 55 '60 *

• f · ’

229 q ·· ·· • «

9999 • - 9

9999

9 9

9 9

9 ·

9 9> .9 9

9 · 9

999 -9

9 «·

9

9

Met Glu Asn His Leu Ile Gly Leu 65 70 Lys Glu Gin Wall Asp Ile Arg Glu 85 Gly Asn Asp Thr ' Lys Lys Phe Asp 100 ALIGN! Thr Tyr Phe His Arg Ser ¹ 115

Phe Val Gln Ala Gln Leu Asn Phe 75 ^'30

Phe Glu. Arg Gin Ala Phe · ⁹⁵

Phe Val Ile Phe Ser‘Lys Glu Lys

105 HO (2) Information for SEQ ID NO: 105:

(i) Sequence characteristics:

_ (A) Length :. 335 amino acids ------------------------ (B) Type: amino acid (D) 'Topology: linear (ii) Molecule type: protein (iii) Hypothetical : YES (vi) Original source:

(A) Organism: Helicobacter pylori (ix) Properties:>

(A) Name / Key ': misc_charakter + (B) Location: 1 ... 335', '

Met (xi) Asn Description Ile Lys sequence: SEQ ID NO: Leu Val 105: '; '' Gly Gly Leu Ile Leu Lys Ile 1 5 10 15 Dec Ser Leu Asn Ala 20 May His Leu Trp Gly Lys Gin Asp Asn Ser Phe Leu Gly Ile Gly Glu Arg Ala Tyr Lys Ser 40 Gly Asn Tyr Ser Lys Ala Ala Ser 45 Tyr Phe 50 Lys Lys Ala Cys Asn Asp 55 Gly Val Ser Glu Gly Cys Thr Gin Leu 65 Gly Ile Ile Tyr Glu 70 Asn Gly Gin Gly Thr Arg Ile Asp Tyr Lys 75 Lys Ala Leu Glu Tyr 85 Tyr Lys Thr Ala Cys Gin Ala Asp Asp Glu 95 Gly Cys Phe Gly Leu Gly Gly Leu Tyr Asp 105 Glu Gly Leu Gly Thr Ala Gin Asn Tyr Gin Glu Ala Ile Asp 120 Ala Tyr Ala Cys Ala Cys Val Leu 125 Lys His 130 Pro Glu Ser Cys Tyr Asn Leu Gly Ile Ile Tyr Asp Arg Lys Ile 145 Lys Gly Asn Ala Ala. 150 Gin Ala Val Thr Tyr Tyr Gin Lys Ser Cys 155 Asn Phe Asp Met Ala 165 Lys Gly Cys Tyr Ile Leu Gly Thr Ala Tyr Glu ¹⁷⁵ ' Lys Gly Phe Leu Glu Wall «R Lys Gin Ser Asn 185 His Lys Ala Val Ile Tyr 190 Tyr Leu Lys Ala Cys Arg Leu Ash, 200 Glu Gly Gin Ala Cys Arg Ala Leu Gly Ser 210 Leu Phe Glu Asn Gly Asp 215 Ala Gly Leu Asp Glu Asp Phe Glu _ø 220

230

Wall 225 Ala Phe Asp Tyr Leu 230 Gin Lys Ala Cys < Ala 235 • · · · Leu I · · Asn • * J · · · · Asn Ser Gly 240 Gly Cys Ala Ser Leu 245 Gly Ser Met Tyr Met 250 Leu Gly Arg Tyr Val Lys 255 Lys Asp For Gin 2S0 Lys Ala Phe Asn Tyr 265 Phe Lys Gin Ala Cys Asp Met 270 Gly Ser Ala 275 Wall Ser Cys Ser Arg 280 .Met Gly Phe Met Tyr 285 Ser Gin Gly Asp Thr 290 Wall' 'Ser Lys Asp Leu 295 Arg Lys .Ala Leu Asp 300 Asn Tyr Glu Arg Gly 305 Cys Asp Met Gly Asp 310 Glu Wall Gly Cys Phe 315 Ala Leu Ala Gly Met .320. Tyr ’ Tyr. ' Asn Met Lys 325 Asp Lys Glu Asn Ala 330 Xle Met Ile Tyr Asp Lys 335 Gly Arg Cys Gly - Lys Tyr 355 Leu 340 Gly Met Lys Gin Ala 345 Cys Glu Asn Leu Thr: Lys Leu 350

(2) Information for SEQ ID NO: 106:

(i) Sequence characteristics:

(A) Length: 193 amino acids (B) Type: amino acid (D) Topology: linear (ii) Molecule type: protein (iii) Hypothetical: YES (vi) Original source:

(A) Organism: Helicobacter pylori (ix)

(A) Name / Key: misc_charakter (B) Location: 1 ... 193 (xi) Sequence Description: SEQ ID NO: 106:

Met Lys Glu Lys Asn Phe Trp Pro Leu Gly Ile Met. Ser Wall Leu Ile 1 5 10 15 Dec Phe Gly Leu Gly Ile Wall Val Phe Leu Val Val Phe Leu Lys Asn 20 May 25 30 Ser For Lys Asn Asp Leu Val Tyr Phe Lys Gly His Asn Glu Wall Asp 35 40 45 Leu Asn Phe Asn Ala Met Leu Lys Thr Tyr Glu Asn Phe Lys Ser Asn 50 55 60 Tyr Arg Phe Ser Wall Gly Leu Lys Leu Thr Glu Ser For Lys Thr 65 70 75 80 For Ile Leu Pro Tyr Phe Ser Lys Gly Thr His Gly Asp Lys Lys Ile 85 90 95 Gin: Glu Asn Leu Leu Asn Asn Ala Leu Ile Flying Glu Lys Ser Asn Thr

• ·

231

Leu Tyr Al 115

Ile Gin Val

Leu Gly-Thr

Leu Glu

Val Phe Lys

Lys

100 ALIGN!

Gin Leu

Tyr Leu

Leu Asp

Gly Asp

Asn-Lys

Gin

Ala

Cys

150

Lys

Glu

For

Phe

135

Lys

Wall

Leu Lys For Ala Leu Asp Ser

121 ¹²⁵ Tyr Pro Ser Gin

140

Asn Ala Cys Glu ^{Pro Leu}

Gly Arg Lys Ile Leu Phe

170

Glu Leu Ile Leu

Leu Ala 190

Pro Asn

Arg Leu

Phe Asp 160.-Lys Phe 175

Phe, Phe (2) Information for SEQ ID NO: 107:

(i) Sequence characteristics:

(A) Length: 289 amino acids (B) Type: amino acid (D) Topology: linear (ii) Molecule type: protein (iii) Hypothetical: YES (vi) Original source:

(A) Organism: Helicobacter pylori (ix)

(A) Name / Key: misc_charakter (B) Location: 1 ... 289 (xi) Sequence Description: SEQ ID NO: 107:

Leu Gly Ile Asn Met Cys Ser Lys Lys Ile Arg Asn Leu Ile Leu Cys 1 5 10 15 Dec Phe Gly Phe Ile Leu Ser Leu Cys Ala Glu Glu Asn Ile Thr Lys Glu 20 May 25 30 Asn Met Thr Glu Thr Asn Thr Thr Glu Glu Asn Thr For Lys Asp Ala 35 40 45 For Ile Leu Leu Glu Glu Lys Arg Ala Gin Thr Leu Glu Leu Lys Glu 50 55 60 Glu Asn Glu Wall Ala Lys Lys Ile Asp Glu Lys Ser Leu Leu Glu Glu 65 70 75 80 Ile His Lys Lys Lys Arg Gin Leu Tyr Met Leu Lys Gly Glu Leu His 85 90 95 Glu Lys Asn Glu Ser Ile Leu Phe Gin Gin Met Ala Lys Asn Lys Ser 100 ALIGN! 105 110 Gly Phe Phe Ile Gly Wall Ile Leu Gly Asp Ile Gly Ile Asn Ala Asn 115 120 125 For Tyr Glu Lys Phe Glu. Leu Leu Ser Asn Ile Gin Ala Ser For Leu

232 • • • • • · • · • e • · • · «» • • • · · • · 130 135 140 Leu Tyr Gly Leu Arg Ser Gly Tyr Gin Lys Tyr Phe Ala Asn Gly Ile 145 150 155 160 Ser Ala Leu Arg Phe Tyr Gly Glu Tyr Leu Gly Gly Ala Met Lys Gly 165 170 175 Phe Lys Ser Asp Ser Leu Ala Ser Tyr Gin Thr Ala Ser Leu Asn Ile 180 185 190 Asp Leu Leu Met Asp Lys For Ile Asp Lys Glu Lys Arg Phe Ala Leu 195 200 205 Gly Ile Phe Gly Gly Wall Gly Wall Gly Trp Asn Gly Met Tyr Gin Asn 210 215 220 Leu Lys Glu Ile Arg Gly Tyř Ser Gin For Asn Ala Phe Gly Leu Wall 225 230 235 240 Leu Asn Leu Gly Wall. Ser Met Thr Leu Asn Leu Lys His Arg Phe Glu 245 250 .255 Leu Ala Leu Lys Met For For Leu Lys Glu Thr Ser Gin Thr Phe Leu -Phe- 260 265 270 Tyr -Tyr- -Lys- -Ser- -Thr- -Asn- Tle TyrTyr -T18 · Ser Tyr Asn Tyr Leu

(2) Information for SEQ ID NO: 108:

(i) Sequence characteristics:

(A) Length: 668 amino acids (B) Type: amino acid (D) Topology: linear (ii) Molecule type: protein (iii) Hypothetical: YES, (vi) Original source:

(A) Organism: Helicobacter pylori (ix)

(A) Name / Key: misc_character (B) Location: 1 ... 668 (xi) Sequence Description.-SEQ ID NO: 108:

Met Arg Lys Leu Phe Ile For Leu Leu Leu Phe Ser Ala Leu Glu Ala 1 5 10 15 Dec Asn Glu Lys Asn Gly Phe Phe Ile Glu Ala Gly Phe Glu Thr Gly Leu 20 May 25 30 Leu Glu Gly Thr Gin Thr Gin Glu Lys Arg His Thr Thr Thr Lys Asn 35 40 45 Thr Tyr Ala Thr Tyr Asn Tyr Leu For Thr Asp Thr Ile Leu Lys Arg 50 55 60 Ala Ala Asn Leu Phe Thr Asn Ala Glu Ala Ile Ser Lys Leu Lys Phe 65 70 75 80 Ser Ser Leu Ser For Wall Arg Wall Leu Tyr Met Tyr Asn Gly Gin Leu 85 90 95 Thr Ile Glu Asn Phe Leu For Tyr Asn Leu Asn Asn Wall Lys Leu Ser 100 ALIGN! 105 110 Phe Thr Asp Ala Gin Gly Asn Thr Ile Asp Leu Gly wall Ile Glu Thr

• ft • ftft · · · · ·

234 ft ft , · · • · · ftftftft • · • • · • · • · ft «Ftftft · • • · · 530 535 540 Wall Gin Gin Leu Ser Tyr Gly Gly Gly Ile Asp Leu Leu Leu Asp Phe 545 550 555 560 Badly Thr Thr Tyr Ser Asn Lys Asn Ser For Thr Gly Ile Gin, Thr 'Lys 565 570 575 Arg Asn Phe Ser Ser Ser Phe Gly Ile Phe Gly Gly Leu Arg Gly Leu 580 585 590 Tyr Asn Ser Tyr Tyr Wall Leu Asn Lys Wall Lys Gly Ser Gly Asn. Leu 595 600 605 Asp Wall Ala Thr Gly Leu Asn, Tyr. Arg Tyr Lys His Ser Lys. : Tyr 'Ser 610 615 620 Wall Gly Ile Ser Ile For Leu, Ile'Gin Arg • Lys Ala Ser Wall Val Ser 625 630 635 640 Ser. Gly Gly Asp Tyr Thr Asn Ser Phe Wall Phe Asn Glu Gly Ala Ser 645 650 655. His Phe Lys Wall Phe Phe Asn Tyr Gly Trp Wall Phe

660 665 (2) Information for SEQ ID NO: 109:

(i) Sequence characteristics:

(A) Length: 63 amino acids (B) Type: amino acid (D) Topology: linear (ii) Molecule type: protein (iii) Hypothetical: YES (vi) Original source:

(A) Organism: Helicobacter pylori (ix)

(A) Name / Key: misc_charakter (B) Location: 1 ... 63 (xi) Sequence Description: SEQ ID NO: 109:

Met Asn Thr Glu Ile Leu Thr Ile Met Leu Wall Wall Ser Wall Leu Met 1 5 10 15 Dec Gly Leu Wall Gly Leu Ile Ala Phe Leu Trp Gly Wall Lys Ser Gly Gin 20 May 25 30 Phe Asp Asp Glu Lys Arg Met Leu Glu Ser Wall Leu Tyr Asp Ser Ala 35 40 45 Ser Asp Leu Asn Glu Ala Ile Leu Gin Glu Lys Arg Gin Lys Asn 50 55 60

(2) Information for SEQ ID NO: 110:

(i) Sequence characteristics:

(A) Length: 406 amino acids (B) Type: amino acid (D) Topology: linear

235 • · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · (2) Molecule type: protein (iii) Hypothetical: YES (vi) Original source:

(A) Organism: Helicobacter pylori (ix)

(A) Name / Key: misc_character (B) Location: 1 ... 406 (xi -) - Description — Sequence -: - SEQ — TBNO: -1-10 -: -—---

Met 1 Wall Phe Phe His 5 Lys Lys Ile Ile Leu 10 Asn Phe Ile Tyr Ser 15 Dec Leu Met Wall Ala Phe 20 May Leu Phe His Leu Ser 25 Tyr Gly Wall Leu Leu 30 Lys Ala Asp Gly Met 35 Ala Lys Lys Gin Thr 40 Leu Leu Wall Gly Glu 45 , Arg Leu Wall Trp Asp 50 Lys Leu . Thr 'Leu Leu 55 Gly Phe Leu Glu Lys 60 Asn His Ile For Gin 65 Lys Leu Tyr Tyr Asn 70 Leu Ser Ser Gin Asp 75, Lys, Glu Leu Ser Ala 80 Glu Ile Gin Ser Asn 85 Wall Thr Tyr Tyr Thr 90 Leu Arg Asp Ala Asn 95 Asn Thr Leu Ile Gin 100 ALIGN! Ala Leu Ile For Ile 105 Ser Gin Asp Leu Gin 110 Ile His Ile Tyr Lys 115 Lys Gly Glu Asp Tyr 120 Phe Leu Asp Phe Ile 125 For Ile Wall Phe Thr 130 Arg Lys Glu Arg Thr 135 Leu Leu Leu Ser Leu 140 Gin Thr Ser For Tyr 145 Gin Asp Ile Wall Lys 150 Ala Thr Asn Asp For 155 Leu Leu Ala Asn Gin 160 Leu Met Asn Ala Tyr 165 Lys Lys Ser Wall For 170 Phe Lys Arg Leu Wall 175 Lys Asn Asp Lys Ile 180 Ala Ile Wall Tyr Thr 185 Arg Asp Tyr Arg Wall 190 Gly Gin Ala Phe Gly 195 Gin For Thr Ile Lys 200 Met Ala Met Wall Ser .205 Ser Arg Leu His Gin 210 Tyr Tyr Leu Phe Ser 215 His Ser Asn Gly Arg 220 Tyr Tyr Asp Ser Lys 225 Ala Gin Glu Wall Ala 230 Gly Phe Leu Leu Glu 235 Thr For Wall Lys Tyr 240 Thr Arg Ile Ser Ser 245 For Phe Ser Tyr Gly 250 Arg Phe His For Wall 255 Leu Lys Wall Lys Arg 260 For His Tyr Gly Wall 265 Asp Tyr Ala Ala Lys 270 His Gly Ser Leu Ile 275 His Ser Ala Ser Asp 280 Gly Arg Wall Gly Phe 285 Ile Gly Wall

Lys Ala 290 Gly Tyr Gly Lys Wall 295 Wall Leu 305 Wall Tyr Ala His Met 310 Ser Ala Ser Phe Wall Lys Lys 325 Gly Gin Ile Leu Ser Thr Gly 340 For His Leu His For Ile Asn 355 For Leu Gly Tyr Ile 360 Gly Lys 370 Gin Arg Glu Wall Phe 375 Leu Lys 385 Tyr Leu Leu Glu Leu Glu Glu Leu Gly 405 Phe 390 Phe Lys Thr

0 • · 0 0 • 0 0 0 0 00 0 0 0 * 0 0 0 0 0 236 0 • 0 .0 0 0 0 0 0 0 0 0 0 0 0 0 00 0 0 0 0 0 0 0 0 0 0 0 Glu Ile His Leu Asn Glu Leu Arg 300 Phe Ala Asn Gly Leu Lys Lys Gly 315 320 Ile Gly Arg Wall Gly Ser Thr Gly 330 335 Phe Gly Wall Tyr Lys Asn Ser Arg 345 350 Arg Thr Ala Lys Ser Lys Leu His 365 Glu Lys Ala Gin Tyr Ser Lys .Gin 380 His Ser Phe Glu Lys Asn Ser Phe 395 400

(2) Information for SEQ ID NO: III:

(i) Sequence characteristics:

(A) Length: 296 amino acids (B) Type: amino acid (D) Topology: linear (ii) Molecule type: protein (iii) Hypothetical: YES (vi) Original source:

(A) Organism: Helicobacter pylori (ix) Properties:

(A) Name / Key: misc_charakter (B) Location: 1 ... 296 (xi) Sequence Description: SEQ ID NO: 111:

Leu Phe Leu Wall Lys Lys Ile Gly Wall Wall Ile Met Ile Leu Wall Cys 1 5 10 15 Dec Phe Leu Ala Cys Ser Gin Glu Ser Phe Ile Lys Met Gin Lys Lys Ala 20 May 25 30 Gin Glu Gin Glu Asn Asp Gly Ser Lys Arg For Ser Tyr Wall Asp Ser 35 40 45 Asp Tyr Glu Wall Phe Ser Glu Tlnr-Ile Phe Leu Gin Asn Met Wall Tyr 50 55 60 Gin For Ile Glu Glu Arg Asn Ala Phe Phe Gin Leu Thr Lys Asp Glu 65 70 75 80 Asp Asn Ser Phe Asn For Glu Asn Ser Wall Ile Leu Leu Asn Glu For 85 90 95 Ser Asp Asn Ser Glu Lys Asn Leu Leu Ser Tyr For Asn Asp For Asn 100 ALIGN! 105 110 Asn Asn Glu Asp Asn Ala Asn Asn Ser Gin Lys Asn For Phe Leu Tyr 115 120 125 Lys For Lys Arg Lys Thr Lys Asn For Lys Leu Ile Glu Tyr Ser Gin 130 135 140 Gin Asp Phe Tyr For Leu Lys Asn Gly Asp Ile Ile Met Ser Lys Glu 145 150 155 160 Gly Asp Gin Trp Leu Ile Glu Ile Gin Ser Lys Ala Leu Lys Arg Phe 165 170 175 Leu Lys Asp Gin Asn Asp Lys Asp Arg Gin Ile Gin Thr Phe Thr Phe 180 185 190

237 · «· · · · '' '« «« · · · 237 237 · · · · ······· ·· · ·· ··

Asn Asp Thr Lys Thr Gin Ile Ala Gin Ile Ly3 Gly Lys Ile Ser Ser 195 200 205 Tyr Wall Tyr Thr Thr Asn Asn Gly Ser Leu Ser Leu Arg Phe Tyr 210 215 220 Glu Ser Phé Leu.Leu Glu Lys Lys Ser Asp Asn Val Tyr Thr Ile Glu 225 230 235 240 Asn. ' Lys Ala Leu Asp Thr Met Glu Ile Ser Lys Cys. Gin Met Wall Leu 245 250 - 255 Lys Lys- , His. .Ser .Thr Asp Lys. Leu Asp Ser Gin His Lys.Ala Ile Ser  * 260 265 270 Ile Asp Leu Asp Phe Lys Lys Glu Arg Phe Lys · Ser Asp Thr Glu Leu 275 280 7285 Phe Leu Glu- Cys Leu Lys Glu Ser 290 295

(2) Information for SEQ ID NO: 112:

(i) Sequence characteristics:

(A) Length: 248 amino acids (B) Type: amino acid (D) Topology: linear (ii) Molecule type: protein, (iii) Hypothetical: YES (vi) Original source:

(A) Organism: Helicobacter pylori (ix)

(A) Name / Key: misc_charakter (B) Location: 1 ... 248 (xi) Sequence Description: SEQ ID NO: 112:

Val Ser Tyr Asp Asn Thr Asp Asp Tyr Tyr Phe For Arg Asn Gly Val 1 5 10 15 Dec Ile Phe Ser Ser Gly Leu Thr Met Ser Pro Ser Ser Gly Thr 20 May 25 30 Leu Asn Ser Trp Asn Gly Leu Gly Gly Asn Val Arg Asn Lys Val 35 ⁴⁰ 45 Tyr Gly Lys His His Leu Gin Lys Tyr Leu Leu Ile 50 55 60 Asp Leu Ile Ala Arg Phe Lys Thr Gin Gly Gly Tyr Ile Phe Arg Tyr 65 70 75 80 Asn Thr Asp Asp Tyr Leu For Leu Asn Ser Thr Phe Tyr Met Gly Gly 85 90 95 Val Thr Thr Phe Arg Asn Gly Ser Ile Thr For Lys Asp 100 ALIGN! ¹⁰⁵ 110 Glu Phe Gly Leu Gly Gly Asp Gly Ile Phe Thr Ala Ser Thr ¹¹⁵ 120 ¹²⁵ Glu Leu Ser Tyr Gly Val Leu Lys Ala Ala Lys Met, Arg Leu Ala Trp 130 , 135 ·· 140

Phe 145 Phe Asp Phe Gly Phe 150 Leu Thr Phe Phe Tyr Asn Ala 165 For Thr Thr Wall. Wall Gly Ala 180 Gly Phe Glu Arg Leu Gin Ile 195 Glu Trp Ile Ser For 200 For Ile 210 Ala Phe Phe Asn Gin 215 Trp Lys 225 Gly Leu Cys  Phe Asn 230 For Asn Glu Phe Ser Met Gly 245 Thr Arg Phe

• * · ·· 9 99 9 9 9 • · • 9 9 9 9 238 • · · · · · · · · · · 9 9 9 9 9 9 9 9 9 9 9 ······· ·· 9 9 9 9 9 Phe Lys Thr Pro Thr Arg Gly Ser 155 160 Thr Ala Asn Phe Lys Asp Tyr Gly 170 175 Ala Thr Trp Arg. Ala. Ser Thr Gly 185 190 Met Gly For Leu Val Leu Ile Phe 205 Gly Asp Gly Asn Lys Lys Cys 220 Met Asn Asp Tyr, Thr Gin His Phe 235 240

(2j Information for SEQ ID NO: 113:

(i) Sequence characteristics:

(A) Length: 335 amino acids (B) Type: amino acid (D) Topology: linear.

(ii) Molecule type: protein (iii) Hypothetical: YES (vi) Original source:

(A) Organism: Helicobacter pylori (ix)

(A) Name / Key: misc_charakter (B) Location: 1 ... 335 (xi) Sequence Description: SEQ ID NO: 113:

Wall 1 Gin His Phe Asn 5 Phe Leu Tyr Lys Asp 10 Ser Leu Phe Ser Ile 15 Dec Ala Leu Phe Thr Phe 20 May Ile Ile Ala Leu Val 25 Ile Leu Leu Glu Gin 30 Ala Arg Ala Tyr Phe 35 Thr Arg Lys Arg Asn ^- Lys Lys Phe Leu Gin 45 Lys Phe Ala Gin Asn 50 Gin Asn Ala Tyr Ala 55 Ser Ser Glu Asn Leu 80 Asp Glu Leu Leu Lys 65 His Ala Lys Ile Ser 70 Ser Leu Met Phe Leu 75 Ala Arg Ala Tyr Ser 80 Lys Ala Asp Wall Glu 85 Met Ser Ile Glu Ile- 90 Leu Lys Gly Leu Leu 95 Asn Arg For Leu Lys 100 ALIGN! Asp Glu • Glu Lys Ile Ala Wall Leu Asp Leu 110 Leu Ala

239

Lys Asn Tyr Phe Ser Wall Gly Tyr Leu Gin Lys Thr Lys Asp Thr Wall 115 120 125 Lys Glu Ile Leu Arg Phe Ser For Arg Asn Wall Glu Ala Leu Leu Lys 130 135 140 Leu Leu His Ala Tyr Glu Leu Glu Lys Asp Tyr Ser Lys Ala Leu Glu 145 150 155 160 Thr Leu Glu Cys Leu Glu Glu Leu Glu Wall For Lys Ile Glu Thr Ile 165 ' 170 175 Lys. Asn Tyr Leu Tyr and Leu Met His Leu Ile Glu Asn Lys Glu Asp Ala 180 185 190 Ala Lys Ile Leu His Wall Ser Lys' Ala Ser Leu Asp Leu Lys Lys Ile 195 200 .205 Ala Leu Asn His Leu Lys Ser His Asp Glu Asn Leu'Phe Trp Gin • Glu 2X0 215 220 Ile Asp Thr Thr Glu Arg Leu Glu Asn Wall Ile Asp Leu Leu Trp Asp 225 230 235 240 Met Asn Ile For Ala Phe Ile Leu Glu Lys His Ala Leu Leu Gin Asp 245 250 255 Ile. Ala Arg Ser Gin Gly Leu Leu Leu Asp His Lys Pro Cys Gin Ile 260 265 270 Phe Glu Leu Glu Wall Leu Arg Ala Leu Leu His Ser Pro Ile Lys Ala 275 280 285 Ser Leu Thr Phe Glu Tyr Arg Cys Lys His Cys Lys Gin -Ile Phe For 290 295 300 Phe Glu Ser His Arg Cys For Val Cys Tyr Gin Leu Ala Phe Met Asp 305 310 315 320 Met Wall Leu. Lys Ile Ser Lys Lys Thr His Ala Met Gly Val Asp 325 330 335

(2) Information for SEQ ID NO: 114:

(i) Sequence characteristics:

(A) Length: 413 amino acids (B) Type: amino acid (D) Topology: linear (ii) Molecule type: protein (iii) Hypothetical: YES (vi) Original source:

(A) Organism: Helicobacter pylori (ix)

(A) Name / Key: misc_character (B) Location: 1 ... 413 (xi) Sequence Description: SEQ ID NO: 114 _:

240 • ·

Met 1 Arg Lys Ile Phe 5 Ser Tyr Ile Ser Lys Val Leu Phu Ile Gly 10 15 Dec Wall Wall Tyr Ala Glu For Asp Ser Lys Wall Glu Ala Leu Glu Gly Arg 20 May 25 - 30 Lys Gin Glu Ser Ser Leu Asp Lys Lys Ile Arg Gin Glu Leu Lys Ser 35 40 45 “Lys Glu “Leu” Lys Asn Lys Glu .Leu Lys Asn Lys Asp .Leu Lys Asn Lys 50 55 60 .Glu Glu Lys Lys Glu Thr Lys Ala Lys .Arg Lys Pro.Arg Ala. Glu Wall '65 - 70 75 '80 His His Gly Asp Ala Lys Asn For Thr 'For -Lys, .Tle ..Thr Pro .For 'Pro Lys 85 90 95  Ile Lys “Gly Ser Ser Lys Gly Wall Gin Asn Gin Gly Val. Gin Asn Asn 100 ALIGN! 105 .110 Ala For Lys -For Glu Glu Lys Asp Thr Thr For·. .Gin Ala. .Thr ..Glu .Lys 115 120 125 Asn Lys Glu Thr Ser For Ser Ser Gin Phe Asn Ser Ile Phe Gly Asn 130 135 140 For Asn Asn Ala Thr Asn Asn Thr Leu Glu Asp Lys Val Val Gly Gly 145 150 155 160 . Ile Ser Leu Leu Wall Asn Gly Ser For Ile Thr Leu Tyr Gin Ile -Gin 165 170 175 Glu Glu Gin Glu Lys Ser Lys Wall Ser Lys Ala Gin Ala. Arg Asp Arg 180 185 190 Leu Ile Ala Glu Arg Ile Lys Asn Gin Glu Ile Glu Arg Leu Lys Ile 195 200 205 His Wall Asp Asp Asp Lys Leu Asp Gin Clu Met Ala. Met Met. Ala Gin 210 215 220 Gin Gin Gly Met Asp Leu Asp : His Phe Lys Gin Met. Leu Met Ala Glu 225 230 235 240 Gly His Tyr Lys Leu Tyr Árg Asp Gin Leu Lys Glu His. Leu Glu Met 245 250 255 Gin Glu Leu Leu Arg Asn Ile Leu Leu Thr Asn Val Asp Thr Ser Ser 260 265 270 Glu Thr Lys Met Arg Glu Tyr Tyr Asn Lys His Lys Glu Gin Phe Ser 275 280 285 Ile For Thr Glu Ile Glu Thr Wall Arg Tyr Thr Ser Thr Asn Gin Glu 290 295 300 Asp Leu Glu Arg Ala Met Ala Asp For Asn Leu Glu Val Pro Gly Wall 305 310 315 320 Ser Lys Ala Asn Glu Lys Ile Glu Met Lys Thr Leu Asn Pro Gin Ile 325 330 335 Ala Gin Wall Phe Ile Ser His Glu Gin Gly Ser Phe Thr Pro Val Met 340 345 350 Asn Gly Gly Gly Gly Gin Phe Ile Thr Phe Tyr Ile Lys Glu Lys Arg 355 360 365 Gly Lys Asn Glu Wall Ser Phe Ser Gin Ala Lys Gin Phe Ile Ala Gin 370 375 380 Lys Leu Wall Glu Glu Ser Lys Asp Lys Ile Leu Glu Glu His Phe Glu 385 390 395 400 Lys Leu Arg Wall Lys Ser Arg Ile Wall Met Ile Arg Glu

405 410

241 • '0 0 · · · 0 0 0 .0 0 0 0 0 0 0 0 0

0000 00 0 .0 0 00 (2) Information for SEQ ID NO: 115:

(i) Sequence characteristics:

(A) Length: 186 amino acids (B) Type: amino acid (D) Topology: linear (ii) Molecule type: protein (iii) Hypothetical: YES (vi) Original source:

______ JA) __ Organism: _Helicobacter-pylori --- (ix) Properties:

(A) Name / Key: misc_charakter (B) Location: 1 ... 186

(xi) Description SEQ ID NO: 115: . Met Ile Lys Arg Ile Ala Cys Leu Ser Ala Ser Leu Ala 1 5 10 15 Dec Leu Ala Gly Glu Val Asn, Gly Phe Phe Met Gly Ala Gly Tyr Gin Gin 20 May 25 ³⁰ Gly Arg Tyr Gly For Tyr Asn Ser Asn Tyr Ser Asp Trp Arg His Gly 35 ⁴⁰ 45 Asn Asp Leu Tyr Gly Leu Asn Phe Lys Leu Gly Phe Val 50 55 60 Asn Lys Trp Phe Gly .Ala Arg Val Tyr Phe Leu Asp Trp Phe Asn 65 70 75 80 Thr Ser Gly Thr Glu His Thr Lys Thr Asn Leu Leu Thr Gly Gly 85 90 95 Gly Gly Asp Leu Ile Val Asn Leu Leu Asp Lys 100 ALIGN! 105 110 Gly Leu Ile Gly Gly Val Gin Leu Ala Gly Asn Thr Trp 115 120 125 Tyr Asp Val Asn Gin Thr Arg Phe Leu Trp Asn Leu Gly Gly 130 135 140 Arg Met Arg Val Gly Asp Arg. Ser Ala Phe Glu Ala Gly Val Lys Phe 145 150 155 160 For Met Val Asn Gin Gly Lys Asp Val Gly Leu Ile Arg Tyr Tyr 165 170 175 Ser Trp Tyr Val Asp Thr Phe Thr Phe 180 185 (2) Information for SEQ ID NO: 116:

(i) Sequence characteristics:

(A) Length: 242 amino acids (B) Type: amino acid ········ 1-) · · · · ··· ··· (D) Topology: linear (ii) Molecule type: protein (iii) 'Hypothetical: YES (vi) Original source :.

(A) Organism: Helicobacter pylori (ix) Properties:

(A) Name / Key: .. (B) Location: 1 misc_charaktér ... .242 (xi) Sequence description: SEQ ID NO: 116 Met 1 Lys Lys Phe Phe Ser 4 Gin Ser Leu Leu Ile .Ile Ser Met 10 15 Asn Ala Val Ser Gly Met Asp Gly Val Phe. Leu Gly Ala Gly Tyr Leu Gin Gly Gin Ala 34 Gin Met His Ala Asp Ile. Asn Ser Gin Lys 40 Gin Ala Thr Asn Ala Thr Ile Lys Gly Phe Asp, Ala: Leu Leu Gly Tyr 55 60 Gin 65 Phe Phe Glu Lys 70 His Phe Gly Leu Le 75 80 Asp Tyr Ala His Ala Asn 84 Ser Ile Lys Leu Lys Asn For Asn Tyr Asn 90 95 Ser Glu Ala Ala Gin Val Ala Ser Gin Ile Leu Gly Lys Asn Arg Leu Thr Asn Ile 116 Ala Asp Pro Arg Thr Phe Glu Pro Asn Met 120 125 Leu Thr Tyr Gly Gly Ala 130 Met Asp Val Met Asn Asn Asn 135 140 140 Gly 145 Ile Met Ser Leu Gly 151 Ala Phe Gly Gly Leu Ala Gly Asn 155 150 Ser Trp Leu Met Ala Thr Pro Ser Phe Glu Gly Ile Leu Val Glu 170 175 Ala Leu Val Ser Lys Lys Ala Thr Ser Phe Gin Gly Ala Arg Leu Arg Ile 198 Leu Lys His Ser Ser Ile Glu Ala Gly Val 200 205 Lys Phe Pro Met Leu Lys Lys Asn Pro Tyr Ile Thr Ala Asp 225 Thr Ile Gly Phe Arg Arg 230 Phe Val Tyr Ser Trp Tyr Val Asn Tyr Val Phe 235 240

243 (· · '· tt tt · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · (2) Information for SEQ ID NO: 117:

(i), Sequence characteristics:

(A) .Length: 256 / amino acids (B) Type: amino acid (D). Topology: linear (ii) Molecule type: protein (iii). Hypothetical: YES (vi) Original source:

—_-_____ (A) _Organism: Helicobacter pylori --------------- (ix) Features:

(A) Name / Key: misc_charakter (B) Location: 1 ... 256 (xi) Sequence Description: SEQ ID NO: 117:

Met 1 Gly Tyr Ala Ser 5 Lys Leu Ala Leu Lys 10 Ile Cys Leu Wall Gly 15 Dec Leu Cys Leu Phe Ser 20 May Thr Leu Gly Ala Glu 25 His Leu Glu Gin Lys Gly , Asn Tyr Ile Tyr 35 Lys Gly Glu Glu Ala 40 Tyr Asn Asn Lys Glu 45 Tyr Glu Arg Ala Ala 50 Ser Phe Tyr Lys Ser 55 Ala Ile Lys Asn Gly 60 Glu Ser Leu Ala Ťyr 65 Ile Leu Leu Gly Ile 70 Met Tyr Glu Asn Gly 75 Arg Gly Wall For Lys 80 Asp Tyr Lys Lys Ala 85 Wall Glu Tyr Phe Gin 90 Lys Ala Wall Asp Asn 95 Asp Ile For Arg Gly 100 ALIGN! Tyr Asn Asn Leu Gly 105 Wall Met Tyr Lys Glu 110 Gly Lys Gly Wall For 115 Lys Asp Glu Lys Lys 120 Ala Wall Glu Tyr Phe 125 Arg Ile Ala Thr Glu 130 Lys Gly Tyr Thr Asn 135 Ala Tyr Ile Asn Leu 140 Gly Ile Met Tyr Met 145 Glu Gly Arg Gly Wall 150 For Ser Asn Tyr Ala 155 Lys Ala Thr Glu Cys 160 Phe Arg Lys Ala Met 165 His Lys Gly Asn Wall 170 Glu Ala Tyr Ile Leu 175 Leu Gly Asp Ile Tyr 180 Tyr Ser Gly Asn Asp 185 Gin Leu Gly Ile Glu 190 For Asp Lys Asp Lys 195 Ala Wall Wall Tyr Tyr 200 Lys Met Ala Ala Asp 205 Wall Ser Ser Ser Arg 210 Ala Tyr Glu Gly Leu 215 Ser Glu Ser Tyr Arg 220 Tyr Gly Leu Gly

· 9.9 ’9.9 9 9 9 9 9 9

244 '1 « • 99 99 • · 9 9 9 9 • • • • 9 • • · Wall Glu Lys Asp Lys Lys Lys Ala Glu Glu Tyr Met Gin Lys Ala Cys 225 230 235 240 Asp Phe Asp Ile Asp Lys Asn Cys Lys Lys Lys Asn Thr Ser Ser Arg 245 250 255

(2) Information for SEQ.ID NO: 118:

(i) Sequence characteristics:, (A) Length: 657: amino acids (B) Type: - amino acid (D) Topology: linear (ii) Molecule type: 'protein (iii) Hypothetical: YES, (vi) Original source:

-—-— (A) Organism: Helicobacter pylori __________________ _____ _ ..

(ix) Features:

(A) Name / Key: misc_charakter (B) Location: 1 ... 657 (xi) Sequence Description: SEQ ID NO: 118:

Met Arg Lys Leu Phe Ile For Leu Leu Leu Phu Ser Ala Leu Glu Ala

5 10 15

Asn Glu Lys Asn Gly Phe Ile-Glu Ala Gly Phe Thr Gly Leu .25 · 30

Leu Glu Gly 35 Thr Gin Thr Gin' Glu 40 Lys Arg His Thr Thr 45 Thr Lys Asn Thr Tyr 50 Ala Thr Tyr Asn Tyr 55 Leu For Thr Asp Thr 60 Ile Leu Lys Arg Ala 65 Ala Asn. Leu Phe Thr 70 Asn Ala Glu_ Ala Ile 75 Ser Lys Leu Lys Phe 80 Ser Ser Leu Ser For 85 Wall Arg Wall Leu Tyr 90 Met Tyr Asn Gly Gin 95 Leu Thr Ile Glu Asn 100 ALIGN! Phe Leu For Tyr Asn 105 Leu Asn Asn Wall Lys 110 Leu Ser Phe Thr Asp 115 Ala Gin Gly Asn Wall 120 Ile Asp Leu Gly Wall 125 ile Glu Thr Ile For 130 Lys His Ser Lys Ile 135 Wall Leu For Gly Glu 140 Ala Phe Asp Ser Leu 145 Lys Ile Asp For Tyr 150 Thr Leu Phe Leu For 155 Lys Ile Glu Ala Thr 160 Ser Thr Ser Ile Ser 165 Asp Ala Asn Thr Gin 170 Arg Wall Phe Glu Thr 175 Leu Asn Lys Ile Lys 180 Thr Asn Leu Wall Wall 185 Asn Tyr Arg Asn Glu 190 Asn Lys Phe Lys Asp 195 His Glu Asn His Trp 200 Glu Ala Phe Thr For 205 Gin Thr Ala Glu Glu 210 Phe Thr Asn Leu Met 215 Leu Asn Met Ile Ala 220 Wall Leu Asp Ser Gin 225 Ser Trp Gly Asp Ala 230 Ile Leu Asn Ala For 235 Phe Glu Phe Thr Asn 240

245 '· ** 11.1 '· · (· • Φ • · • · -1 : 111 111.1 «· ···» • l · 1 i 1  · Λ '·· 1 · - · , · 1 • · • '1 or · · • 11 .11 l · 9 <: <· 1 ·· 1 · «• · (« • · 1 : 1 .1 » Ser For Thr Asp Cys Asp Asn Asp For Ser Lys Cys Val Asn For Gly 245 250 255 Thr Asn Gly Leu Wall Asn Ser Lys Wall Asp Gin Lys Tyr Val Leu Asn 260 265 '270 Lys Gin Asp Ile Wall Asn Lys Phe Lys Asn Lys Ala Asp .Leu Asp Wall 275 280 235 Ile Wall Leu Lys Asp Ser Gly Wall Wall Gly Leu Gly Ser. Asp ' Ile Thr 290 Γ. . 295 300 For Ser Asn Asn Asp Asp Gly Lys His Tyr Gly Gin.. Leu. Gly Wall Wall 305 310 315 320 Ala Ser • Ala Leu Asp For Lys Lys Leu Phe Gly Asp Asn .Leu Lys' .Thr 325 330 335 Ile- Asn Leu Glu Asp ' Leu Arg Thr Ile Leu. His. Glu * Phe. Ser His Thr 340 345 350 Lys Gly Tyr Gly His Asn Gly Asn Met Thr Tyr Gin Arg val For Wall 355 360 365 Thr Lys Asp Gly Gin Wall Glu Lys Asp Ser Asn Gly Lys Pro Lys Asp 370 375 380 Ser Asp Gly Leu For Tyr Asn Wall Cys Ser Leu Tyr Gly Gly Ser Asn 335 390 395 400 Gin For Ala Phe For Ser Asn Tyr For Asn Ser Ile Tyr His Asn Cys 405 410 415 Ala Asp Wall For Ala Gly Phe Leu Gly Wall Thr Ala Ala Val Trp Gin 420 425 ^ 30 Gin Leu Ile Asn Gin Asn Ala Leu For Ile Asn Tyr Ala Asn Leu Gly 435 440 445 Ser Gin Thr Asn Tyr Asn Leu Asn Ala Ser Leu: Asn Thr.Gin Asp Leu 450 455 460 Ala Asn Ser Met Leu Ser Thr Ile Gin Lys Thr Phe Val Thr Ser Ser 465 470 475 480 Wall Thr Asn His His Phe Ser Asn Ala Ser Gin Ser Phe Arg Ser · For 485 490 495 Ile Leu Gly Wall Asn Ala Lys Ile Gly Tyr Gin Asn Tyr Phe Asn Asp 500 505 510 Phe Ile Gly Leu Ala Tyr Tyr Gly Ile Ile Lys Tyr Asn Tyr Ala Lys 515 520 52S Ala Wall Asn Gin Lys Wall Gin Gin Leu Ser Tyr Gly Gly Gly Ile Asp 530 535 540 Leu Leu Leu Asp Phe Ile Thr Thr Tyr Ser Asn Lys Asn Ser For Thr 545 550 555 560 Gly Ile Gin Thr Lys Arg Asn Phe Ser Ser Ser Phe Gly Ile Phe Gly 565 570 575 Gly Leu Arg Gly Leu Tyr Asn Ser Tyr Tyr Wall Leu Asn Lys Wall Lys 580 585 590 Gly Ser Gly Asn Leu Asp •Wall Ala Thr Gly Leu Asn Tyr Arg Tyr Lys 595 600 605 His Ser Lys Tyr Ser Wall Gly Ile Ser Ile For Leu Ile Gin Arg Lys 610 615 620 Ala Ser Wall Wall Ser Ser Gly Gly Asp Tyr Thr Asn Ser Phe Wall Phe 625 630 635 640 Asn Glu Gly Ala Ser His Phe Lys Wall Phe Phe Asn Tyr Gly Trp Wall - 645 650 655

Phe

··

246 (2) Information for SEQ ID NO: 119:

(i) Sequence characteristics:

(A) .Length: 167.'amino acids (B) Type: amino acid (D) Topology: linear '(ii). Molecule type: protein (iii) Hypothetical: YES (vi) Original source:

Qrgani with _mus . Hel icobacter pylori - ~ (ix)

(A) Name / Key: misc_charakter (B) Location: 1 ... 167 (xi) Sequence Description: SEQ ID NO: 119:

Met 'Lys Leu Val Ser Leu Ile Val A ± a Leu Val Phe Cys .'Phe .. Leu 1 5 10 15'

Gly Ala Val Glu Leu Gly Val Tyr Gin Thr Gin'Glu Phe Leu Tyr

25 30

Met Lys Ser Ser Phe Val Glu His Asn Gly Lys Phe Tyr

40 45

Ala Tyr Gly Ser Lys Ala Lys Lys Asp Lys

55 60

Leu Asn For As Lys Leu Arg Asn Arg Ser Lys Gly Val Val

70

Phe Leu Ser Asp Leu Ile Val Gly Glu Glu Ser Tyr Lys Gly

-5 90 95

Lys Ala Tyr Asn Phr Tyr Asp Gly Lr Thr Tyr His Val Arg Val Thr

100 105 110

Gin Asn Ser Asn Gly Leu Glu Phr Thr Ser Ser Tyr Asp Lys Trp

115 120 125

Gly Tyr Val Gly Lys Thr Php Thr Lys Arg Leu Ser Asp Glu Glu

130

Ile Lys As Leu Lys Leu Lys Arg Phe Asn Leu Asp Glu Val Leu Lys 145 150 155 160

Thr Leu Lys Asp Ser Pro Ile (2) Information for SEQ ID NO: 120:

(i) Sequence characteristics:

(A) Length: 294 amino acids (B) Type: amino acid (D) Topology: linear (ii) Molecule type: protein, • 000

247 ,·· 0 · 0 · 0 (vi) Original / Source:

(A) ..Organism: Helicobacter pylori (ix) Features:

• (A) Name / Key: misc_charakter (B) Location: 1 ... 294 í-x-il Signature Sequence: SEO ID NO: 120:

Met 1 Ser Asn Gin Ala 5 ' Ser His Leu Asp Asn 10 Phe. .-Met · Asn .Ala Lys 15 Dec Asn For Lys Ser Phe 20 May Phe Asp Asn Lys Gly 25 Asn Thr Lys Phe Ile 30 Ala Tle Thr Ser Gly 35 Lys Gly Gly wall Gly Lys Ser Asn Ile Ser 45 Ala Asn Leu Ala Tyr 50 Ser Leu Tyr .Lys Lys 55 Gly Tyr Lys Wall Gly 60 Wall Phe Asp Ala Asp 65 Ile Gly Leu Ala Asn 70 Leu Asp Wall Ile Phe 75 Gly Wall Lys Thr His 80 .Lys Asn • Ile Leu His 85 Ala Leu Lys Gly Glu 90 .Ala Lys Leu Gin Glu 95 Ile Ile Cys Glu Ile 100 ALIGN! Glu For Gly Leu Cys' 105 Leu Ile For Gly. Asp .110 Ser Gly Glu Glu Ile 115 Leu Lys Tyr Ile Ser , 120 Gly Ala Glu Ala Leu, 125 Asp Arg Phe Wall Asp 130 Glu Glu Gly Wall Leu 135 Ser Ser Leu Asp Tyr 140 Ile Wall Ile Asp Thr 145 Gly Ala Gly Ile Gly 150 Ala Thr Thr Gin Ala 155 Phe Leu Asn Ala Ser 160 Asp Cys Wall Wall Ile 165 Wall Thr Thr For Asp 170 For Ser Ala Ile Thr 175 Asp Ala Tyr Ala Cys 180 Ile Lys Ile Asn Ser 185 Lys Asn Lys Asp Glu 190 Leu Phe Leu Ile Ala 195 Asn Met Wall Ala Gin 200 For Lys Glu Gly Arg Ala Thr Tyr Glu Arg 210 Leu Phe Lys Wall Ala 215 Lys Asn Asn Ile Ala 220 Ser Leu Glu Leu His 225 Tyr Leu Gly Ala Ile 230 Glu Asn Ser Ser Leu 235 Leu Lys Arg Tyr Wall 240 Arg Glu Arg Lys Ile 245 Leu Arg Lys Ile Ala 250 For Asn Asp Leu Phe 255 Ser Gin Ser Ile Asp 260 Gin Ile Ala Ser Leu 265 Leu Wall Ser Lys Leu 270 Glu Thr Gly Thr Leu Glu Ile For Lys Glu Gly Leu Lys Ser Phe Phe Lys Arg

275 280 285 Leu Leu Lys Tyr Leu Gly. 290 (2) Information for SEQ ID NO: 121:

· * • 99 9 ft. 9 9 9

10 ·· 99 «

248 ·· <··· t · · (i) Sequence characteristics:

(A) Length: 372 amino acids.

• (B) Type: amino acid (D) Topology: linear (ii) Molecule type: protein • (iii) · Hypothetical: YES, (vi) -Original source:

(A) Organism: Helicobacter pylori - (ix) Features: ---------- ----- ----- (A) Name / Key: misc_character (B) Location: 1 ... 372 (xi) Description of sequence: SEQ ID NO: 121:

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

• · _ _x - '' · ··· · ··

249. · · · · · · · · ·

• · · · · · · ·

Ser Phe Lys Thr Leu Lys Wall Leu Asp Lys Ala Asn Glu wall Ser Tyr 325 330 335, For Ser Tyr Ser Leu Asn For His Phe Ile Asp Ile Wall Tyr Thr Tyr 340 345 350 Asn Arg Ser His Tle Lys His Ile Arg Phe Asn Met Ala Tyr Leu Asn 3S5 360 '365 Ser Leu Leu Lys _t j, 3 70

2) Information for SEQ ID NO: 122:

(i) Sequence characteristics:

(A). Length: 978 amino acids ^! (B) Type: amino acid (D) Topology: linear (ii) Molecule type: protein (iii) Hypothetical: YES (vi) Original source:

(A) Organism: Helicobacter pylori (ix)

(A) Name / Key: misc_character (B) Location: 1 ... 978 ', (xi) Sequence Description: SEQ ID NO: 122:

Met 1 Lys Lys Arg Lys 5 His Wall Ser Lys Lys 10 Wall Phe Asn Wall Ile 15 Dec Ile Leu Phe Wall Ala 20 May Wall Phe Thr Leu Leu 25 Wall Wall Ile His Lys 30 Thr Leu Ser Asn Gly 35 Ile His Ile Gin Asn 40 Leu Lys Ile Gly Lys 45 Leu Gly Ile Ser Glu 50 Leu Tyr Leu Lys Leu 55 Asn Asn Lys Leu Ser 60 Leu Glu Wall Glu Arg 65 Wall Asp Leu Ser Ser 70 Phe Phe His Gin Lys 75 For Thr Lys Lys Arg 80 Leu Glu Wall Ser Asp 85 Leu Ile Lys Asn Ile 90 Arg Tyr Gly Ile Trp 95 Ala Wall Ser Tyr Phe 100 ALIGN! Glu Lys Leu Lys Wall 105 Lys Glu Ile Ile Leu 110 Asp Asp Lys Asn Lys 115 Ala Asn Ile Phe Phe 120 Asp Gly Asn Lys Tyr 12S Glu Leu Glu Phe For 130 Gly Ile Lys Gly Glu 135 Phe Ser Leu Glu Asp 140 Asp Lys Asn Ile Lys 145 Leu Lys Ile Ile Asn 150 Leu Leu Phe Lys Asp 155 Wall Lys Wall Gin Wall 160 Asp Gly Asn Ala His 165 Tyr Ser For Lys Ala 170 Arg Lys Met Ala Phe 175 Asn Leu Ile Wall Lys ISO For. Leu Wall and Glu For 185 Ser Ala Ala Ile Tyr 190 Leu Gin Gly Leu Thr 195 Asp Leu Lys Thr ¹ r Ile 200 Glu Leu Lys Ile Asn 205 Thr Ser For Met Lys 210 Ser Leu Ala Phe Leu 215 Lys in. For Leu Phe * .. Gin 220 Arg Gin Ser Gin Lys Asn Leu Lys Thr Trp Ile Phe Asp Lys Ile Glh Phe Ala Ser Phe

250 • · • • • · · • '· • • • · · · • · • • · • • · • · · • • · • · and • • 9 9 • · · 99 9 9 • ·· 0 225 Lys Ile Asp 230 Asn Ala Leu Ile Lys Ala Asn 23 5 Phe Thr for Ser Glu 240 Phe Ile Pro Ser 24S 250 Glu Asn Ser Val Val Lys Ala Thr Leu 255 Ile Lys Pro Ser Val 260 265 Val Phe Asn As Gly Leu Ser For Ile. Lys. 270 Met. Asp Lys 275 Thr Glu Leu 280 Ile Phe Lys Asn Lys Gin Leu Leu Ile 285 Gin. For Gin Lys 290 Ile Thr Tyr 295 Glu Thr. Met Glu Leu Thr Gly Ser 300 Tyr Ala Thr; Phe Ser ³⁰⁵ Asn Leu Leu 310 Glu Ala. For Lys Leu Glu Val 315 Phe Leu Lys' Thr. , Thr 320 For Asn Tyr Tyr 325 330 .Gly 'Asp Ser Ile Lys Asp Leu Leu Ser. ' Ala ' 335 Tyr Lys Wall Val Leu 340 345 Leu'Ssp Lys Ile Ser Met Pro Ser Ser Ala 350 Asp Leu Lys 355 Leu Thr Leu 360 Gin Phe Leu Lys Asn Thr For Leu 365 Phe Ser ' Wall Gin 370 Gly Ser Val 375 Gn Glu Gly Thr Phe Ser 380 Leu Tyr Asn Ile For 385 Leu Tyr Thr 390 Gin Ser Ala - Gin Ile Asn Leu 395 Asp Ile Ala Gin Glu 400 Tyr Gin Tyr Ile 405 410 Tyr Ile His Thr Arg Tyr Ala Asn 415 Met Leu Asp Leu Asp 420 425 Ala Lys Gly Gin Lys 430 Asn Leu Ser 435 Leu Asp Ser 440 ’ Leu Val His Lys Asn 445 Thr Asn Asn Asn Ile 450 Asn Met Arg 455 '' / Ser Tyr Asp For Asn Asn Thr Gin 460 Glu Asp For Gin Thr 465 Asn Phe Thr 470 Leu Asp Leu Lys Ser Leu His ⁴⁷⁵ Ser Ile Ile Gin Glu ⁴⁸⁰ Gly Glu Asn Ser 485 490 Glu Val Phe Arg Lys Ile Ile Asp Thr Ile 495 Lys Ala Gin Ser Glu 500 505 Asp Lys Phe Thr Lys Asp Val Phe Tyr Ala 510 Thr Gly Asp 515 Thr Leu Lys 520 Ser Leu | Phe Ser 525 Asn For Asp His 530 Ile Gin 535 Ser Val Pro Gin Leu Leu Leu Glu 540 Gly Glu Phe Lys Asp 545 Asn Ala Tyr 550 Thr Phe Lys 555 Lys Lys Ile Lys For 560 Tyr Ser Pro Ile 565 570 Met Asp Tyr Ile Ala Leu Lys Asp Gly Ser Leu 575 Glu Wall Ser Thr Ser 580 585 Asp Phe Val Asn Ile Phe Ala Lys 590 Asp Leu Lys 595 Ile Asn Leu 600 For Ile Tyr Arg Ser His 605 Phe Asp Ser Phe 610 Ser Leu Phe 615 Gly Ser Ile Asn Lys Asp Glu Ile 620 Ser Wall Tyr Thr For 625 Ser Lys Ser 630 Ile Ser Ile Val Lys Gly 635 Asp Gin Lys Asp Ile 640 Thr Leu Asn Asn 645 650 Ile Asp Leu Ser Ile Asp Asp Phe Leu Asp Ser 655 Lys Met

660 € 65 670

'251

For Ala Ile Ala Gly Leu Phe Ser Lys Glu Arg ⁶⁷⁵ 580 685 Ser Lys Glu Ile Gin Asp Glu. Asp Val Phe Ile Ser .Ala. Lys, Gin Arg 690 • 695- / 700 ' Tyr Glu. Lys' Ala. .His-Lys Ile Ile Pro. Ile tSer · Thr Arg. i Ile.His · Ala .705 > in . 710 715, 720 Lys Asp Val Wall Leu Ile Tyr. Lys Lys Met ' Pro Phe Pro Leu.Glu -.Asn 725- 730 . * 735 ..Leu Asp Ile · Wall. Ala, Gin, Asp‘Asp ArgVal Lys, Ile Asp GlyAsn Tyr 740 , 'I 745 '750 Lys Asn’Ala Met Villa Met Ala. Asp, Leu Val His. Gly "Ala" Leu Tyr Leu ⁷⁵⁵ ‘760, 765 Lys Ala His Asn Phe Ser Gly Asp Tyr Ile Asn Thr Ile Leu Gin Lys 770 '775 780 „Ásp- Phe Val -Glu-Gly-Gly-Leu PheThr Leu Ile Gly Ala Leu Glu Asp 785 790 795 800 Gin Val Phe Asn Gly Glu Leu Lys Phe Gin Asn Thr. Ser Leu, Lys Asn 805 810 815 Phe Ala Leu Met Gin Asn Met Val Leu Ile Asn Thr 820 825 830 Leu Ile Val Phe Arg Asn Pro His Leu Gly Ala Gly Tyr Gin Ile 835 840 845 Lys Thr Gly Ser Phe Gly Ile Thr Lys Glu Tyr Leu 850 855 860 Glu Lys Ile Asp Leu Val Gly Lys Thr Leu Asp Ile Ala Gly 865 870 875 ³⁸⁸⁰ Ile Ile Glu Leu Asp Lys Asn Lys Leu Asp Leu Asn Leu Glu Val Ser 885  890  . '895 Thr Ile Lys Ala Leu Ser Asn Val Leu Asn ‘Lys Ile For Ile Val Gly 900 905. 910 Tyr Leu Val Leu Gly Lys Thr Thr Asn Val Asn Val 915 920 925 Lys Gly Thr Leu Asp Lys Pro Lys Thr Gin Val Thr. Leu Ala Ser Asp 930 935 940 Ile Ile Gin Ala For Phe Lys Ile Leu Arg Arg Ile Phe Thr For Ile 945 950 955 960 Asp Ile Ile Wall Asp Glu Val Lys Lys Asn Ile Asp Ser Lys

965 970 975

Leu Lys (2) Information for SEQ ID NO: 123:

(i) Sequence characteristics:

(A) Length: 477 amino acids (B) Type: amino acid (D) Topology: “linear

252 • ΦΦΦ • Φ φ φ -. ..

(ii) Molecule type: protein (iii) Hypothetical: φ · ii ii ii ii ii ii ii ii ii ii ii ii ii YES (vi). Original source:

(A) Organism: Helicobacter pylori (ix)

(A) Name / Key:, misc_character (B) Location: 1 ... 477 (xi) Sequence Description: SEQ ID NO: 123:

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

253 • · · · · · · · · · ·

Phe Thr Ile Leu Gly Asn Phe Tyr 340 For Asp Leu Asp Gly Gin Gin Asn Thr Ala Asp Ile 345 Gly Leu 350 Leu Gin Lys 365 Leu Ala Tyr 380 Lys Ser Leu Gin Ser Lys Lys Asp Ile Leu Asn 355 Met Leu 370 Ile Phe Gly Gin Ala 375 Glu 360 Ash Gin Glu Leu Lys Asn Glu Gin Glu Lys Tyr Arg 385 390 395 400 . Ala Arg. Ala Lys Ile Glu Ser Ser Lys Ala Ser Leu.Asp Ala Ala Asn 405 410 415 _x · Leu Ser. Phe Ala Asn Ile Lys' · Arg. Lys? Tyr Asp Ala.Asn Leu Val Asp .420 425 .430 . Phe Thr Thr, Tyr Leu Arg Gly Leu Thr Thr Arg Phe Asp Ala Glu Val 435 440 '445 , Ala Tyr Asn Leu Ala Leu Asn Asn Tyr Glu Wall Gin‘Lys Ala Asn Tyr 450 455 460 Ile Phe Asn Ser Gly His Lys Ile Asp Asp Tyr Val His 465 470 475 (2) Information for SEQ ID NO: 124:

(i) Sequence characteristics:

(A) Length: 412 amino acids (B) Type: amino acid (D) Topology: linear.

(ii) Molecule type: protein (iii) Hypothetical: YES (vi) Original source:

(A) Organism: Helicobacter pylori (ix)

(A) Name / Key: misc_charakter (B) Location: 1 ... 412 (xi) Sequence Description: SEQ ID NO: 124:

Met 1 Leu Ser Phe Ile 5 Ser Ala Phe Asp Lys 10 Arg Gly Wall Ser Ile 15 Dec Arg Leu Leu Thr Ala 20 May Leu Leu Leu Leu Phe 25 Ser Leu Gly Leu Ala 30 Lys Asp Leu Glu Ile 35 Gin Thr Phe Wall Ala 40 Lys Tyr Leu Ser Lys 45 Asn Gin Lys Ile Gin 50 Ala Leu Gin Glu Gin 55 Ile Asp Ala Leu Asp 60 Ser Gin Glu Lys Wall 65 Wall Ser Lys Trp Asp 70 Asn For Ile Leu Tyr 75 Leu Gly Tyr Asn Asn 80 Ala Asn Wall Ser Asp 85 Phe Phe Arg Leu Asp 90 Ser Thr Leu Met Gin 95 Asn Met Ser Leu Gly 100 ALIGN! Leu Ser Gin Lys Wall 105 Asp Leu Asn Gly Lys 110 Lys Leu Thr Gin Ser 115 Lys Met Ile Asn Leu 120 Glu Lye Gin Lys Lys 125 Ile Leu Glu Leu Lys 130 Lys Thr. Lys Gin Gin 135 Leu Wall Ile Asn Leu 140 Met Ile Asn Gly Ile 145 Glu Asn Tyr Lys Asn 150 Gin Gin Glu Ue Glu 155 Leu Leu Asn Thr Ala 160 Ile Lys Asn Leu Glu 165 Asn Thr Leu Tyr Gin 170 Ala Asn His Ser Ser 175 Ser For Asp Leu Ile Ala Ile Ala Lys Leu Glu Ile Leu Lys Ser Leu Leu

99

Glu Ile Gin 180 Lys Asn Asp Leu Glu 185 Wall Ala Leu Ser Ser 190 Ser His Tyr Ser Met 195 Gly Glu Leu Thr Phe 200 Lys' Glu Asn Glu Ile. 205 Leu Ser .Ile Ala For 210 Lys Asn Phe Glu Phe, 215 Asn Asn Glu Gin Glu 220 Leu His Asn Ile .Ser 225 Ala Thr Asn Tyr Asp 230 Ile Ala Ile Ala Arg 235 Leu Asp Glu Glu ' Lys 240 Ala Gin Lys Asp Ile 245 Thr Leu Ala • Lys Lys 250 Ser Phe Leu-Glu Asp 255 Ile. .Asn Wall Thr Gly 250 Wall Tyr Tyr Phe Arg 265 Ser Lys Gin Tyr'Tyr '270 Asn Tyr Asp Met Phe 275 Ser Wall Ala Leu Ser 280 Ile For Leu For Leu 285 Tyr Gly Lys Gin 290  - 295 - 300 - - - .....— . Ala Lys Leu Wall Glu Gin Lys Lys Lys Glu Ser Leu Ala Phe Lys Ser 305 Glu Wall Glu Asn Ala 310 Lys Asn Lys Thr Arg 315 His Leu Ala Leu Lys 320 Leu Leu Lys Lys Leu 325 Glu Thr Leu Gin Lys 330 Asn Leu Glu Ser Ile 335 Asn Lys Ile Ile Lys 340 Gin Asn Glu Lys Ile 345 Ala Gin Ile Tyr Ala 350 Leu Asp Leu Lys Thr 355 Asn Gly Asp Tyr Asn 360 Ala Tyr Tyr Asn Ala 365 Leu Asn Asp Lys Ile 370 Thr Ile Gin Ile Thr 375 Gin Leu Glu Thr Leu 380 Ser Ala Leu Asn Ser 385 Ala Tyr Leu Ser Leu 390 Gin Asn Leu Lys Gly 395 Leu Glu 400

405 410 (2) Information for SEQ ID NO: 125:

(i) Sequence characteristics:

(A) Length: 137 amino acids (B) Type: amino acid (D) Topology: linear (ii) Molecule type: protein (iii) Hypothetical: YES (knows) Original source:

(A) Organism: Helicobacter pylori · · · · · · · · · · · · ·

255 (ix) Features:. , (A) Name / Key: misc_charakter (B) Location: 1 ... 137 (xi): Sequence Description: SEQ ID NO: 125: *

· Met 'Arg Tle · Val Arg Asn Leu Wall Ser Phe Val Ala Tyr. Ser 1 '' ⁴ 5 ’ 10 .15 . Ser.Ala.Phe Ala Ala. Asp Leu Glu Thr Gly Thr Lys Asn'Asp ‘Lys-Lys 20 May ²⁵  30 Ser Gly Lys .Phe Tyr Lys .Leu His Lys Asn HisGlySer Glu ‘Thr '- <. 35 40, 45 Glu. Thr Lys Asn Asp. Lys ..Lys. Leu Tyr Asp Phe Thr Lys Asn Ser Gly 50 '‘' 55 / 60 Glu Val Glu Val Asp Leu Glu Lys For Asn Leu Lys His Lys 65 ⁷⁰ 75 80 Lys Ser Asp Lys Lys Phe Tyr Leu Ala Lys .; Asn Asn Ile Ala 85 90 95 Glu Gly Val Ser Met Pro Ile Val Asn Phe Asn Lys _t 'Ala Leu Ser Phe 100 ALIGN! 105 110 Gly Pro Tyr Phe Glu Arg Thr Lys Lys Lys. Thr Gin Tyr Met Asp 115 120 125 Gly Gly Leu Met Met His Ile Arg Phe 130 135 (2) Information for SEQ ID NO: 126:

(i) Sequence characteristics:

(A) Length: 309 amino acids (B) Type: amino acid (D) Topology: linear (ii) Molecule type: protein (iii) Hypothetical: YES (vi) Original source:

(A) Organism: Helicobacter pylori (ix)

(A) Name / Key: misc_charakter (B) Location: 1 ... 309 (xi) Sequence Description: SEQ ID NO: 126:

Leu Met For Gin Asn Gin In Leu Val Ile, France Thr Ile Ile Asp Glu Ser Gly 1 5 10 15 Dec Ser Lys Gin Leu Lys Phe Ser Lys Asn Leu Lys Arg Asn Leu Ile Ile 20 May 2 '25 ³⁰ Ser Wall Wall Ile Leu Léu Leu. Ile Val Gly Leu Gly Val Gly Phe Leu 35 40. 45 Lys Phe Leu Ile Ala Lys Met Asp Thr Met Thr Ser‘Glu Arg Asn Ala 50 ⁵⁵ · ' 60 Wall Leu Arg Asp Phe Arg Gly Leu .Tyr Gin Lys Asn Tyr Ala Leu Ala. 65 C ^{Ť 7} °. 75 , · * 'Λ 80

256

Lys Glu Ile Lys Asn ' Lys Arg Glu Glu Leu Phe Ile Val Gly Gin, Lys 85 90 95, Ile Arg Gly Leu Glu Ser Leu Ile Glu Ile Lys Lys Gly Ala Asn Gly 100 ALIGN! 105 110 Gly Gly His Leu Tyr Asp Glu Wall Asp Leu Glu Asn Leu Ser Leu Asn r 115 120 125 Gin Lys His Leu Ala Leu Met Leu Ile. For Asn Gly Met For Leu Lys 130 135 140 Thr Tyr Ser Ala Ile Lys For Thr Lys. Glu Arg Asn .His. For Ile.Lys 145 150 155 160 Lys Ile Lys Gly Wall Glu Ser Gly Ile Asp Phe. Ile, Ala For Leu Asn 165 170 175 Thr For Wall Tyr Ala Ser Ala Asp Gly Ile Wall Asp Phe Wall Lys Thr 180 185 190 Arg Er Šer Asn Ala Gly Tyr Gly Asn Leu Wall Arg Ile Glu .'His Ala .Phe 195 200 205 Gly Phe Ser Ser Ile Tyr Thr His Leu Asp His Val Asn Wall Gin Pro - ™ 2i0 - -. 215. , _____. 220______ ... __ Lys Ser Phe Ile Gin Lys Gly Gin Leu Ile Gly Tyr Ser Gly Lys Ser 225 230 235 240 Gly Asn Ser Gly Gly Glu Lys Leu His Tyr Glu Val Arg Phe Leu Gly 245 250 255 Lys Ile Leu Asp Ala Glu Lys Phe Leu Ala Trp Asp Leu Asp His .Phe 260 265 270 'sGln Ser Ala Leu Glu Glu Asn Lys Phe Ile Glu Trp Lys Asn Leu.Phe 275 280 285 Trp Wall Leu Glu Asp Ile Wall Gin Leu Gin Glu His Val Asp Lys Asp 290 295 300 Thr Leu Lys Gly Gin

305 (2) Information for SEQ ID NO: 127:

(i) Sequence characteristics:

(A) Length: 332 amino acids (B) Type: amino acid (D) Topology: linear (ii) Molecule type: protein (iii) Hypothetical: YES (vi) Original source:

(A) Organism: Helicobacter pylori (ix)

• 090 <'· • 0

257 (Β), Location: 1. ..332 (xi). Sequence description: SEQ ID NO: '127:

Wall Leu Tyr , .Phe • Leu. Thr Ser Lěu Phe Ile. Cys Ser Leu 'Ile .Wall .Leu 1 - . < 5 , 10 ' and. i-5 Trp Ser. Lys Lys Ser. Met. Leu Phe Wall. Asp. Asn Ala - Asn . Lys. : ile .Gin 20 May 25 * · » 30 Gly, Phe His His .Ala Arg Thr , Pro Arg -Ala Gly Gly; Leu : .Gly Ile Phe 35 40 45 Leu Ser. .Phe Ala Leu Ala Cys Tyr Leu Glu For Phe Glu : Met 'For ^: 'Phe 50 55 € 0 Lys Gly For Phe Wall Phe Leu Gly Leu Ser Leu Val Phe Leu Ser Gly 65 70 75 80 Phe ~ Leu Glu Asp Ile Asn Leu Ser Lěu Ser (For Lys Ile Arg Leu Ile 85 90 95 Leu Glh Ala Wall . Gly Wall Wall Cys Ile Ile Ser Ser Thr For Leu Wall 100 ALIGN! 105 110 Wall Ser Asp Phe Ser For Leu Phe Ser Leu For Tyr iPhe Ile Ala Phe 115 120 125 Leu Phe Ala Ile Phe Met Leu Wall Gly Ile Ser Asn Ala Ile Asn Ile Χ3Ό 135 140 Ile Asp Gly Phe Asn Gly Leu Ala Ser Gly Ile Cys ¹ Ala Ile Ala Leu 145 150 155 160 Leu Wall Ile His Tyr Ile Asp For Ser- Ser Leu ’ Ser Cys Leu Leu Ala 165 170 . -r 175 Tyr Met Wall Leu Gly Phe Met Wall Leu Asn Phe ProSer Gly Lys Ile 180 185 . , '· ^Lř 190 Phe Leu Gly Asp Gly Gly Ala Tyr Phe Leu Gly, Leu Val Cys Gly Ile 195 200 - 205 Ser Leu Leu His Leu Ser Leu Glu Gin Lys Ile Ser Val Phe Phe Gly 210 215 220 Leu Asn Leu Met Leu Tyr For Wall Ile Glu Wall Leu Phe Ser Ile Leu 225 230 235 240 Arg Arg Lys Ile Lys Arg Gin Lys Ala Thr Met For Asp Asn Leu His 245 250 255 Leu His Thr Leu Leu Phe Lys Phe Leu Gin Gin Arg Ser Phe Asn Tyr 260 265 270 For Asn. For Leu Cys Ala Phe Ile Leu Ile Leu Cys Asn Leu For Phe 275 280 285 Ile Leu Ile Ser Val Leu Phe Arg Leu Asp Ala Tyr Ala Leu Ile wall 290 295 300 Ile Ser. Leu Wall Phe Ile Ala Cys Tyr Leu Ile. Gly Tyr Ala Tyr Leu 305 310 315 320 Asn Arg Glh Wall Cys Ala Leu Glu Lys Arg Ala Phe

325 330 (2) Information for SEQ ID NO: 128:

(i) Sequence characteristics:

(A) Length: 271 amino acids (B) Type: amino acid ’.

,; . <ř ·

Ϊ · '·%. ·· e''-', ^ø '·

258 (B) Type: amino acid (D) Topology: linear

(.ii) Molecule type: protein (iii) Hypothetical: YES (vi) Original source:

(A) Organism: Helicobacter pylori (ix)

(A) Name / Key: misc_charakter

------- (B) Location: 1 ... 271 (xi) Sequence Description: SEQ ID NO: 128:

Met 1 Asn Ile Phe Lys 5 Arg Ue Ile Cys Wall 10 Thr Ala Ile Wall Leu 15 Dec Gly Phe Phe Asn Leu 20 May Leu Asp Ala Lys His 25 His Lys Glu Lys Lys 30 Glu Asp His Lys Ile 35 Thr Arg Glu Leu Lys 40 Wall Gly Ala Asn For 45 Wall For His Ala Gin 50 Ile. Leu Gin Sec Wall 55 Wall Asp Asp Leu Lys 60 Glu. Lys: Gly Ile Lys 65 Leu Wall Ile Wall Ser 70 Phe Thr Asp Tyr Wall 75 Leu For Asn Leu Ala 80 Leu Asn Asp Gly Ser 85 Leu Asp Ala Asn Tyr 90 Phe Gin His Arg For 95 Tyr Leu Asp Arg Phe 100 ALIGN! Asn Leu Asp Arg Lys 105 Met His Leu Wall Gly 110 Leu Ala Asn Ile His 115 Wall Glu For Leu Arg 120 Phe Tyr Ser Gin Lys 125 Ile Thr Asp Xle Lys 130 Asn Leu Lys Lys Gly 135 Ser Wall Ile Ala Wall 140 For Asn Asp For Ala 145 Asn Gin Gly Arg Ala 150 Leu Ile Leu Leu His 155 Lys Gin Gly Leu Ile 160 Ala Leu Lys Asp For 165 Ser Asn Leu Tyr Ala 170 Thr Glu Phe Asp Ile 175 Wall Lys Asn For Tyr 180 Asn Ile Lys Ile Lys 185 For Leu Glu Ala Ala 190 Leu Leu For Lys Wall 195 Leu Gly Asp Wall Asp 200 Gly Ala Ile Ile Thr 205 Gly Asn Tyr Ala Leu 210 Gin Ala Lys Leu Thr 215 Gly Ala Leu Phe Ser 220 Glu Asp Lys Asp Ser 225 For Tyr Ala Asn Leu 230 Wall Ala Ser Arg Glu 235 Asp Asn Ala Gin Asp 240 Glu Ala Ile Lys Ala 245 Leu Ile Glu Ala Leu 250 Gin Ser Glu Lys Thr 255 Arg Lys Phe Ile Leu 260 Asp .Thr Tyr Lys Gly 265 Ala Ile Ile For Ala 270 Phe

. 259 • · ···· (2) Information for, SEQ ID NO: 129:,, (i) Sequence characteristics: '- / (A) Length: 316 amino acids (B) Type: - amino acid (D) Topology: linear (Ii) Type of molecule: protein.

i »'I (iii) Hypothetical: YES (vi) Original source:

__________________ (A) Organism: Helicobacter pylori (ix) Properties:

(A) Name / Key: misc_charakter (B) Location: 1 ... 316 (xi) Sequence Description: SEQ ID NO: 129:

Met Gin Glu Phe Ser Leu 1 Glu Asn Asp Phe 5 Leu Lys Thr Ser Asn 20 May For Ser Leu Tyr Gin 35 Asp Glu Ile Ala Tyr 50 Glu Thr Leu Ala Leu 65 Met For Leu Tyr Glu 70 Lys Ile Asp For Phe 85 Leu Glu Lys Arg Leu 100 ALIGN! Phe Lys Thr For Ala 115 Ser Glu Ser Ala Ser 130 Ile For Ile Asn Wall 145 Glu Ile Ala Gin Ile ISO Leu Ser Wall Phe Wall 165 Ser Arg Gin Asn Leu 180 Gin Ala Gin Tyr Gin 195 Ile Asn Gin His Ser 210 Thr Gly Wall Lys Ser

225,. '· '23 Ο

Trp. Cys Asp Phe Ile Glu Arg Asp Phe 15 Dec Leu 10 Leu Ilé .Asn Lys Gly Ala Ile Cys _t Gly - Ala 25 '' 30 Phe .cys Glu , Ala Ile Thr Lys Ser . Ala . Phe 40 ’ 45 Lys Leu Lys Gly Lys Lys Ala Lys Glu . Ile. 55 60 t Lys Asp Ile Leu Gin Ala Ser Ser Ala Leu 75 80 Asp For Asn Asn Gly Tyr Ile Ser Leu Glu 90 95 Asp Asp Ala Ile Lys Ser Ile Asp Glu Ala 105 110 Leu Asn Arg For Asn Wall Met Ile Lys Wall 120 125 Phe Glu Wall Ile Ser Ala Leu Ala Gin Ala 135 140 Thr Leu Wall Phe Ser For Lys Ile Ala Gly 155 160 Ala Lys Glu Ala Arg Lys Arg Ala Wall Ile 170 175 Phe Asp Lys Glu Ile Asp For Leu Wall For 185 190 Ser Gly, Ile Met Asn Ala Thr Glu Cys Tyr 200 205 Ala Asn Lys Leu Ile Ser Thr Leu Phe Ala 215 220 Asn Ser Leu Ala Lys Asp Tyr Tyr Ile Lys '· ⁴ : 235 240

and! '', r '-: i ·. ‘. > '

and

260

Ala Leu Cys Phe Lys Asn Ser Xle Asn Thr Ala For Leu Asp Ala Leu 245 2S0 of 255 Asn Ala Tyr Leu Leu Asp For Asn Thr Glu Cys Gin Thr For Leu Lys 260 265 270 Ile Thr Glu Ile Glu Ala Phe Lys Lys Glu Leu Lys Thr His Asn Ile 275 280 285 Asp. Leu. • Glu. Asn. Thr., .Ala. Gin Lys Leu Leu Lys .Glu Gly / Leů Ile Ala 290 295 300 Phe. Lys Gin Ser Phe- Glu. Lys Leu Leu Ser Ser Phe

305 310 315 (1). Information for SEQ ID NO: 130:

(i) Sequence characteristics:

-------- (A) Length: 260 amino acids (B) Type: amino acid (D) Topology: linear (ii) Molecule type: protein (iii) Hypothetical: YES (vi) Original source:

(A) Organism: Helicobacter pylori (ix)

(A) Name / Key: misc_charakter · (B) Location: 1 ... 260 (xi) Sequence Description: SEQ ID NO: 130:

Met Lys Thr Asn Gly His Phe Lys Asp Phe Ala Trp Lys Lys Cys Phe 1 5 10 15 Dec Leu Gly Ala Ser Wall Wall Ala Leu Leu Wall Gly Cys Ser For His Ile 20 May 25 30 Ile Glu Thr Asn Glu Wall Ala Leu Lys Leu Asn Tyr His For Ala Ser 35 40 45 Glu Lys Wall Gin Ala Leu Asp Glu Lys Ile Leu Leu Leu Arg For Ala 50 55 60 Phe Gin Tyr Ser Asp Asn Ile Ala Lys Glu Tyr Glu Asn Lys Phe Lys 65 70 75 80 Asn Gin Thr Thr Leu Lys Wall Glu Glu Ile Leu Gin Asn Gin Gly Tyr 85 90 95 Lys Wall Ile Asn Wall Asp Ser Ser Asp Lys Asp Asp Phe Ser Phe Ala 100 ALIGN! 105 110

·· ····

• ’·« ·· • * · ·· • · ···· • <4 • r ·· • ·. • 261 - ‘· - · • · ···,! ··· · • ·. · •. · • · • • • • · « · « »· · · · ·· ’· Gin Lys Lys Glu Gly Tyr Leu Ala Wall Ala Met Asn Gly Glu Ile Wall 115 120 125 Leu Arg For Asp For Lys Arg Thr Ile. Gin Lys Lys Ser Glu For Gly 130 135 140 Leu Leu Phe Ser Thr Gly Leu Asp Lys Met Glu Arg Wall Leu Ile For 145 150 155 160 Ala Gly Phe Wall Lys Wall Thr Ile Leu Glu-Pro Met Ser Gly Glu Ser * * 165 170 175 ' Leu Asp Ser Phe Thr Met Asp Leu Ser Glu Leu Asp Ile Gin Glu Lys ‘180 185 190 Phe Leu Lys .Thr Thr His Ser Ser His Ser Gly Gly Leu Wall Ser Thr • 1 195 200 205 Met Wall Lys Gly Thr Asp Asn Ser Asn Asp. Ala Ile Lys Ser Ala Leu -210 215 220 Asn Lys Ile Phe Ala Ser Ile Met Gin Glu Met Asp Lys Lys Leu Thr , 225 230 235 24 0 Gin Arg Asn Leu Glu Ser Tyr Gin Lys Asp Ala Lys Glu Leu Lys Asn —_ · _— 245 - - 250 - 255 Lys Arg Asn Arg

260 (2) Information for SEQ ID NO: 131:

(i) Sequence characteristics:

(A) Length: 1382 amino acids '' (B) Type: amino acid (D) Topology: linear (ii) Molecule type: protein (iii) Hypothetical: YES (vi) Original source:

(A) Organism: Helicobacter pylori (ix)

(A) Name / Key: misc_charakter (B) Location: 1 ... 1382 (xi) Description of Sequence: SEQ ID NO: 131:

Leu Asn Phe Asn Leu Thr Ala Asn Gly Ala Leu Asn Phe Asn Gly · ♦ ··

262. · • ····

·· ··

1 Tyr Ala . For Ser 5 Leu Thr Lys Ala Leu 10 Met Asn Wall Ser Gly 15 Dec Gin Phe Wall Leu 20 May Gly.Asn Asn Gly Asp Ile 25 Asn Leu Ser Asp Ile 30 · Asn Ile Phe Asp Asn 35 Ile Thr Lys Ser Wall 40 Thř Tyr Asn Ile Leu 45 Asn Ala Gin Lys Gly 50 .Xle Thr Gly Ile Ser 55 Gly Ala Asn Gly Tyr 60 Glu Lys Ile Leu Phe 65 Tyr Gly Met Lys Ile 70 Gin Asn Ala Thr Tyr 75 Ser Asp Asn Asn Asn 30 Ile Gin Thr Trp Ser 85 Phe Ile Asn For Leu 90 Asn Ser Ser Gin Ile 95 Ile Gin Glu Ser Ile 100 ALIGN! Lys Asn Gly Asp Leu 105 Thr Ile · Glu. Wall Leu 110 Asn Asn For Asn Ser 115 Ala Ser Asn Thr Ile 120 Phe Asn Ile Ala For 125 Glu Leu Tyr Asn Tyr 130 ^: Gin Asp Ser Lys Gin 135 Asn For Thr Gly Tyr 140 Ser Tyr Asp Tyr Ser 145 Asp Asn Gin Ala Gly 150 Thr Tyr Tyr Leu Thr 155 Ser Asn Ile Lys Gly 160 Leu Phe Thr For Lys 165 Gly Ser Gin Thr For 170 Gin Thr For Gly Thr 175 Tyr Ser For Phe Asn 180 Gin For Leu Asn Ser 185 Leu Asn Ile Tyr Asn 190 Lys Gly Phe Ser Ser 195 Glu Asn Leu Lys Thr 200 Leu. Leu Gly Ile Leu 205 Ser Gin Asn Ser Ala 210 Thr Leu Lys Glu Met 215 Ile Glu Ser Asn Gin 220 Leu Asp Asn Ile. Thr 225 Asn Ile Asn Glu Wall 230 Leu Gin Leu Leu Asp 235 Lys Ile Lys Ue Thr 240 Gin Ala Gin Lys Gin 245 Ala Leu Leu Glu Thr 250 Ile Asn His Leu Thr 255 Asp Asn Ile Asn Gin 260 Thr Phe Asn Asn Gly 265 Asn Leu Wall Ile Gly 270 Ala Thr Gin Asp Asn 275 Wall Thr Asn Ser Thr 280 Ser Ser Ile Trp Phe 285 Gly Gly Asn Gly Tyr 290 Ser Ser For Cys Ala 295 Leu Asp Ser Ala Thr 300 Cys Ser Ser Phe Arg 305 Asn Thr Tyr Leu Gly 310 Gin Leu Leu Gly Ser 315 Thr Ser For Tyr Leu 320 Gly Tyr Ile Asn Ala 325 Asp Phe Lys Ala Lys 330 Ser Ile Tyr Ile Thr 335 Gly Thr Ile Gly Ser 340 Ser Asn Ala Phe Glu 345 Ser Gly Gly Ser Ala 350 Asp Wall Thr Phe Gin 355 Ser Ala Asn Asn Leu 360 Wall Leu Asn Lys Ala 365 Asn Ile Glu Ala Gin 370 Ala Thr Asp Asn Ile 375 Phe Asn Leu Leu Gly 380 Gin Glu Gly Ile Asp 385 Lys Ile Phe Asn Gin 390 Gly Asn Leu Ala Asn 395 Wall Leu Ser Gin Met 400 Ala Met Glu Lys Ile 405 Lys Gin Ala Gly Gly 410 Leu Gly Asn Phe Ile 415 Glu . Asn Ala Leu Ser 420 For Leu Ser Lys Glu 425 Leu For Ala Ser Leu 430 Gin Asp Glu

435. 440 445

263

Thr Leu 450 Gly Gin Leu Ile Gly 455 Gin Asn Asn Leu Asp 460 Asp Leu Leu Asn Asn 465 Ser Gly Wall Met Asn 470 Glu Ile Gin Asn Ile 475 Ile Ser Gin Lys Leu 480 Ser He Phe Gly- Asn 485. Phe Wall Thr For Ser 490 Ile Ile Glu Asn Tyr 495 Leu Ala Lys Gin Ser 500 Leu Lys Ser Met Leu 505 Asp Asp Lys Gly Leu 510 Leu Asn ¹ Phe Ile Giy 515 Gly Tyr Ile Asp. Ala 520 Ser Glu Leu Ser Ser 525 Ile Leu Gly Wall' ile 530 Leu Lys Asp Ile · Thr 535 Asn Prp For Thr Ser 540 Leu Gin Lys Asp Ile 545 Gly Wall wall'' Ala Asn 550 Asp Leu Leu Asn Glu 555 Phe Leu; Gly. Gin Asp , 560 Wall Wall Lys Lys Leu 565 Glu Ser Gin' Gly Leu 570 Wall -Ser Asn Ile ' Ile 575 Asn Asn Wall Ile Ser 580 Gin Gly Gly Leu Ser, 585 Gly Wall • Tyr Asn Gin 590 Gly Leu Gly Ser Wall 595 Leu For For Ser Leu 600 Gin Asn Ala Leu Lys 605 Glu Asn Asp Leu Gly 610 Thr Leu Leu Ser For 615 Arg Gly Leu His Asp 620 Phe Trp Gin Lys Gly 625 Tyr Phe Asn Phe Leu 630 Ser Asn Gly Tyr Wall 635 Phe Wall Asn Asn Ser 640 Ser Phe Ser Asn Ala 645 Thr Gly Gly Ser Leu 650 Asn Phe Wall Ala Asn 655 Lys Ser Ile Ile Phe 660 Asn Gly Asp. Asn Thr 665 Ile Asp Phe Ser Lys 670 Tyr Gin Gly Ala Leu 675 Ile Phe Ala Ser Asn * 680 Gly Wall Ser Asn Ile-. 685 'Asn Ile Thr Thr Leu 690 Ásn Ala Thr Asn Gly 695 Leu Ser Leu Asn Ala 700 Gly Leu Asn Asn Wall 705 Ser Wall Gin Lys Gly 710 Glu Ile Cys Ile Asn 715 Leu Ala Asn Cys For 720 Thr Thr Lys Asn Ser 725 Ser For Ala Asn Ser 730 Ser Wall Thr For Thr 735 Asn Glu Ser Leu Ser 740 Wall His Ala Asn Asn 745 Phe Thr Phe Leu Gly 750 Thr Ile Ile Ser Asn 755 Gly Ala Ile Asp Leu 760 Ser Gin Wall Thr Asn 765 Asn Ser Wall Ile Gly 770 Thr Leu Asn Leu Asn 775 Glu Asn Ala Thr Leu 780 Gin Ala Asn Asn Leu 785 Thr Ile Thr Asn Ala 790 Phe Asn Asn Ala Ser 795 Asn Ser Thr Ala Asn 800 Ile Asp Gly Asn Phe 805 Thr Leu Asn Gin Gin 810 Ala Thr Leu Ser Thr 815 Asn Ala Ser Gly Leu 820 Asn Wall Met Gly Asn 825 Phe Asn Ser Tyr Asp 830 Leu Wall Phe Asn 835 Leu Ser His Ser Wall 840 Ser His Ala Ile Ile 845 Asn Thr Gin Gly Thr 850 Ala Thr Ile, Met Ala 855 Asn Asn Asn For Leu 860 Ile Gin Phe Asn Ala 865 Ser Ser Lys Glu Wall 870 Gly Thr Tyr Thr Leu 875 Ile Asp Ser Ala Lys 880 Ala Ile Tyr Tyr Gly Tyr Asn Asn Gin Ile Thr Gly Gly Ser Ser Leu

• X ·. ··

264 • · · • · · ·· • '· 9 9 ·· '··· 9 9 « • · - 9 9 9 • · · • · · • • a • ·· '9 9 9 9 9 · . «· • • 9> 9 9 9 9 9 885 390 895 Asp Asn Tyr Leu Lys Leu Ile Asp Ile Asn Gly Lys His 900 905 910 Met Val Met Thr Asp Asn Gly Leu Thr Tyr Asn Gly Gin Ala Wall Ser 915 - 920 925 Val Lys Asp Gly Leu Val Val Gly Phe Lys Asp Ser Gin Asn Gin 930 935 940 Tyr-Ile Tyr Thr Ser Ile Leu-Tyr Asn Lys Wall Lys Ile Ala Wall Ser 945 950 955 960 Asn Asp For Ile Asn Asn For Gin Ala For Thr Leu Lys Gin Tyr Ile < 965 970 975 Ala Gin Ile Gin Val Gin Ser Val Asp Ser Ile Asp Gin Ala Gly 980 985 990 Gly Asn Gin Ala Ile Asn Lys Ile Phe Glu Thr Lys Gly 995 1000 1005 Ser Pro Leu Phe Ala For Tyr Tyr Leu Glu Ser His Ser Thr Lys_ Asp 1010 1015 1020 Leu Thr Thr Ile Ala. Gly Asp Ile-Ala Asn Thr Leu Glu Wall Ile Ala 1025 1030 1035 1040 Asn Pro Asn Phe Lys - Asn Asp Ala Thr Asn Ile Leu Gin Ile Asn Thr 1045 1050 1055 Tyr Thr Gin Gin Met Lys Leu Ser Asp Thr Ser Thr 1060 1065 1070 Phe Ala Arg Ser Phe Leu Glu Arg Leu Glu Ala Leu Lys Asn Lys 1075 1080 1085 Arg Phe Ala Asp Ala Ile For Asn Ala Met Asp Val Ile Leu Lys Tyr 1090 1095 ' 1100 Ser Gin Arg Asn Arg Lys Asn Asn Wall Trp Ala Thr Gly Val Gly 1105 1110 · 1115 1120 Gly Ala Ser Phe Ile Gly Gly Thr Gly Thr Leu Tyr Gly Ile Asn 1125 1130 · 1135 Val Gly Tyr Asp Arg Phe Ile Gly Wall Ile Val Gly Gly Tyr Ala 1140 1145 1150 Ala Tyr Gly Tyr Ser Asn Ile Thr Gin Ser Gly Ser 1155 1160 1165 Ser Asn Val Asn Gly Val Tyr Arg Ala Phe Ile Lys Arg Ser 117C 1175 1180 Glu Leu Thr Met Ser Leu Asn Glu Thr Trp Gly Tyr Asn Lys Thr Phe 1185 1190 1195 1200 Ile Asn Ser Tyr Asp Leu Leu Ser Ile Ile Asn Gin Ser Tyr Arg 1205 1210 1215 Tyr Asp Thr Thr Thr Thr Asp Ala Lys Ile Asn Tyr Gly Tyr Asp Phe 1220 1225 1230 Met Phe Lys Asp Lys Ser Ile Phe Lys For Gin Val Gly Leu Ser 1235 1240 1245 Tyr Tyr Tyr Ile Gly Leu Arg Gly Ile Met Asp Asp For 125C 1255 1260 Ile Tyr Asn Alain Asn Ala Asp For Asn Lys Lys Ser Wall 1265 1270 1275 1280 Leu Thr Ile Asn Phe Ala Leu Glu Ser Arg His Tyr Phe Asn. Lys Asn. 1285 1290 1295 Ser Tyr Tyr Phe Ile Ala Asp Val Gly Arg Asp Leu Phe Ile Asn 1300 1305 1310 Ser Met Gly Asp Lys Met • Ile Gly Asn Asn. Thr. Leu Ser

1315 ·, 1320 1325

265

9909 • 9 9 «• 9 9 -0

0 0 ·> · ··· 0. 0

Tyr Arg Asp 1330 Gly Gly Arg Tyr Asn Thr Phe Ala Ile Thr 1340 Gly Gly Glu le Ile Arg Leu Phe Lys Thr Phe Trr Val Asn Ala Gly Ile Gly 1345 1350 1355 · 1360 Ala Arg Phe. Gly Leu Asp Tyr Lys Asp Ile Asn Ile 1365 1370,. - 1375 Gly, Met Arg Tyr Ala Phe 1380 * ^r »'

(2) Information for SEQ ID NO: 132:

(i) Sequence characteristics:

(A) Length: 262 amino acids (B) Type: amino acid (D) Topology: linear (ii) Molecule type: protein (iii) Hypothetical: YES (vi) Original source:, (A) Organism: Helicobacter pylori (ix) :

(A) Name / Key: misc_charakter (B) Location: 1 ... 262 (xi) Sequence Description: SEQ ID NO: 132:

Met 1 Lys Lys Ile Gly Leu Ser Leu Val ys ys Ser Val Leu Ser Leu Gly Phe 5 10 ^{15 Dec} Leu Lys Ala His Glu Val Ser Glu Glu Ile Ala Asp Ile Phe Tyr 20 May 25 30 Lys Leu Asn Ala Lys Glu For Lys Met Lys Ile Asn His Thr Lys Gly 35 40 45 Phe Cys Ala Lys Gly Val Phe Leu For Asn For Gin Ala Arg Glu Asp 50 55 60 Leu Glu Val For Leu Leu Lys Glu Ile Pro Ala Ser Val Arg 65 70 75 80 Tyr Ser Leu Gly Gly Val Ala Met Asp Asp Lys Ser Lys Val Arg Gly 85 90 95 Met Ala Leu Lys Leu Glu Asn Gin Ser Trp Thr Met Val Met 100 ALIGN! 105 110 Leu Asn Thr Glu Ile Asn Phe Ala Lys Asn For Glu Glu Phe Ala Gin 115 120 125 Phe Phe Glu Met Arg Leu For Lys Asn Gly Lys Val Asp Glu Ala Arg 130 135 140 Ile Lys Lys Leu Tyr Glu Glu Val Pro Ser Tyr Arg Asn Phe Ala Ala 145 ISO 155, 160 Tyr Met Lys Ile Gly Thr Ile Ser Ser Ser Val Ala Asn Thr Pro Tyr 165 170 '”-. 175 Tyr Ser Val His Ala Phe Lys Phe, Lys Asp Lys Lys Glu Lys Leu Leu 180 ¹⁸⁵ -Ů · »190 For Ala Arg Trp Lys Phe Val Lys Glu Gly Val Lys Tyr Leu Asn 195 200 ? '’205

4000 • 0 · I • 0 0

266 • 0 0 0 • 0 · 0

0 0 0 .0 · · 000

- 0 · * 00

For Gin Glu Leu Lys Gin Lys Asp Ser Asn Tyr Leu Leu Ser Ser Phe 210 215 220 Gin. Gin His Leu Lys Asn Lys For Ile Glu Tyr Gin Met Tyr Leu Wall 225 230 235 240 Phe Ala  Asn Gin Asn , Asp. Ala Thr Asn Asp Thr Thr • Ala Leu. Trp Lys 245 2SQ 255 Gly Ser Ile Arg Asn Tyr 260

(2) Information for SEQ ID NO: 133:

(i) Sequence characteristics:

(A) Length: 246 amino acids (B) Type: amino acid (D) Topology: linear (ii) Molecule type: protein (iii) Hypothetical: YES (vi) Original source:

(A) Organism: Helicobacter pylori (ix)

(A) Name / Key: misc_character (B) Location: 1 ... 246 (xi) Sequence Description: SEQ ID NO: 133:

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

267

Wall Asn Asn Thr His Thr 195 Ile Asn 210 Ser Asn 225 Ala Asn Tyr Leu Gin

Ser Val Glu Gly Thr Ala Asn Ile Ser Ser Wall Ile 230 Phe Phe 245 Ser

Val Gly 'As G Arg Val Gly' Ser Gly Ala Gly _;

186 f lao

Thr Leu Asn Leu Asn Ala Asn Lys Val Thr

200 205

Ala Tyr Lys Thr Ser Gin Asn Val Gly .215 '. '220.

Thr ile Asn Ser Val Leu Asn Gly Glu

235, 240 (2) Information for SEQ ID NO: 134:

(i) Sequence characteristics:

()) Length: 245 amino acids (B) Type: amino acid (D) Topology: linear (ii) Molecule type: protein (iii) Hypothetical: YES (vi) Original source: ’’:

(A) Organism: Helicobacter pylori · (ix) Properties:

(A) Name / Key: misc_character (B) Location: 1 ... 245 (xi) Sequence Description: SEQ ID NO: 134:

Met 1 Ile Lys Lys Thr 5 Leu Ala Ser Wall Leu 10 Leu Gly Leu Ser Leu 15 Dec Met Ser Wall Leu Asn 20 May Ala Lys Glu Cys Wall 25 Ser For Ile Thr Arg 30 Ser Wall Lys Tyr His 35 Gin Gin Ser Ala Glu 40 Ile Arg Ala Leu Gin 45 Leu Gin Ser Tyr Lys 50 Met Ala Lys Met Ala 55 Leu Asp Asn Asn Leu 60 Lys Leu Wall Lys ASp 65 Lys Lys For Ala Wall 70 Ile Leu Asp Leu Asp 75 Glu Thr Wall Leu Asn 80 Thr Phe Asp Tyr Ala 85 Gly Tyr Leu Wall Lys 90 Asn Cys Ile Lys Tyr 95 Thr For Glu Thr Trp 100 ALIGN! Asp Lys Phe Glu Lys 105 Glu Gly Ser Leu Thr 110 Leu Ile For Gly Ala 115 Leu Asp Phe Leu Glu 120 Tyr Ala Asn Ser Lys 125 Gly Wall Lys Ile Phe 130 Tyr Ile Ser Asn Arg 135 Thr Gln _: Lys Asn Lys 140 Ala Phe Thr Leu Lys 145 Thr Leu Lys Ser Phe 150 Lys Léu For Gin wall 155 Šer Glu E F Glu Ser Wall 160 Leu Leu Lys Glu Lys 165 Gly Lys For' Lys Ala 170 wall Arg Arg Glu Leu 175 Wall

V ' ¹ Ϊ. ,

4 '. · .. ·'' ¹ ti * · ί

268 ft ft • · · · ·

Ala Lys Asp Tyr Ala Ile Val Glu Val Gly Asp Thr Leu His Asp 180 185 190 Phe Asp Ala Ile Phe Ala Lys Asp Ala Lys Asn Ser Gin Glu Gin Gin 19S 200 205 Ala bys Wall Leu Gin Asn Ala Gin Lys Phe Gly Thr GlU Trp Ile Ile 210 215 220

Leu Pro Asn 225

Gin Asn

Ser Leu Tyr Trp Glu ²³⁰ Gly'Thr

Lys Lys

Asp Gly For Ile Lys. Ala 235 240 (2) Information for SEQ ID NO: 135:

(i) Sequence characteristics:

(A) Length: 288 amino acids (B) Type: amino acid (D) Topology: linear (ii) Molecule type: protein (iii) Hypothetical: YES (vi) Original source:

(A) Organism: Helicobacter pylori i. '(ix) Features:

(A) Name / Key: misc_charakter (B) Location: 1 ... 288 (xi) Sequence Description: SEQ ID NO: 135:

Leu 1 Trp Cys Leu Lys 5 Thr For Ile Ile Gly 10 His Gly Met Lys Lys 15 Dec Lys Ala Lys Wall Phe 20 May Trp Cys Cys Phe Lys 25 Met Ile Arg Trp Leu 30 Tyr Leu Ala Wall Phe 35 Phe Leu Leu Ser Wall 40 Ser Asp Ala Lys Glu 45 Ile Ala Met Gin Arg 50 Phe Asp Lys Gin Asn 55 His Lys Ile Phe Glu 60 Ile Leu Ala Asp Lys 65 Wall Ser Ala Lys Asp 70 Asn Wall Ile Thr Ala 75 Ser Gly Asn Ala Ile 80 Leu Leu Asn Tyr Asp 85 Wall Tyr Ile Leu Ala 90 Asp Lys Wall Arg Tyr 95 Asp Thr Lys Thr Lys 100 ALIGN! Glu Ala Leu Leu Glu 105 Gly Asn Ile Lys Wall 110 Tyr Arg Gly Glu Gly 115 Leu Leu Wall Lys Thr 120 Asp Tyr Wall Lys Leu 125 Ser Leu Asn Glu Lys 130 Tyr Glu Ile Ile Phe 135 For Phe Tyr Wall Gin 140 Asp Ser Wall Ser Gly 145 Ile Trp Wall Ser Ala 150 Asp Ile Ala Ser Gly 155 Lys Asp Gin Lys Tyr 160 Lys Ile Lys Asn Met 155 Ser Ala · Ser Gly Cys 170 Ser Ile Asp Asn For 175 Ile Trp His Wall Asn 180 Ala Thr Ser Gly Ser 185 Phe Asn Met Gin Lys 190 Ser His

269

Leu Ser Met Trp Asn For Lys Ile Tyr Wall Gly Asp Ile For Wall Leu 195 200 205, Tyr Leu For Tyr Ile Phe Met Ser Thr Ser Asn Lys Arg- Thr Thr Gly 210 215 220 Phe Leu Tyr For Glu Phe Gly Thr Ser Asn Leu> Asp Gly Phe Ile Tyr 225 230 235 l X 240

Leu Gin Phe Tyr'Leu Lys Asn Ser Trp Asp Met Thr Phe 245 250 255

Thr Pro Gin Ile Arg. Leu Asn Phe. Glu Ala 260 265 270

Arg Tyr Ile. Asn Ser Lys Thr Gin Val Phe Ile Gin Cys Ala, Leu Phe 275 "280 <'285 (2) Information for SEQ ID NO: 136:

(i) Sequence characteristics:

(A) Length: 128 amino acids (B) Type: amino acid (D) Topology: linear (ii) Molecule type: protein (iii) Hypothetical: YES (vi) Original source:

(A) Organism: Helicobacter pylori (ix)

(A) Name / Key: misc_charakter '(B) Location: 1st .., 128 -' (xi) Sequence Description: SEQ ID NO: 136:

Leu Met Phe Lys Lys Met Cys Leu Ser Leu Leu Met Ile Ser Gly Wall 1 5 10 15 Dec Cys Wall Gly Ala Lys Asp Leu Asp Phe Lys Leu Asp Tyr Arg Ala Thr 20 May 25 30 Gly Gly Lys Phe Met Gly Lys Met Thr Asp Ser Ser Leu Leu Ser Ile 35 40 45 Thr Ser Met Asn Asp Glu For Wall Wall Ile Lys Asn Leu Ile Wall Asn 50 55 - 60 Arg Gly Asn Ser Cys Glu Ala Thr Lys Lys Wall Glu For Lys Phe Gly 65 70 75 80 Asp Lys Phe Lys Lys Glu Lys Leu Phe Asp His Glu Leu Lys Tyr Ser 85 90 95 Gin Gin Ile Phe Tyr Arg Leu Asp Cys Lys For Asn Gin Leu Leu Glu 100 ALIGN! 105 110 Wall Lys Ile Ile Thr Asp Lys Gly Glu Tyr Tyr His Lys Phe Ser Lys 115 120 125 (2) Information for SEQ ID NO: 137:

(i) Sequence characteristics:

(A) Length: 169 amino acids (B) Type: amino acid

270

(ii) Molecule type: protein (iii) Hypothetical: YES (vi) Original source:

(A) Organism: Helicobacter pylori (ix)

(A) Name / Key: misc_charakter (B) Location: 1 ... 169

... (xi) Description of sequence: SEQ ID NO: 137:

Met Gin Ala Leu Lys Ser Leu Leu Glu Wall Ile Thr Lys Leu Gin Asn 1 5 10 15 Dec Leu Gly Gly Tyr Leu Met His Ile Ala Ile Phe Ile Ile Phe Ile Trp 20 May 25 30 Ile Gly Gly Leu Lys Phe Wall For Tyr Glu Ala Glu Gly Ile Ala For 35 40 45 Phe Wall Ala Asn Ser For Phe Phe Ser Phe Met Tyr Lys Phe Glu Lys 50 55 60 For Ala Tyr Lys Gin His Lys Meť Ser Glu Ser Gin Ser Met Gin Glu 65 70 75 80 Glu Met Gin Asp Asn For Lys Ile Wall Glu Asn Lys Glu Trp · His Lys 85 90 95 Glu Asn Arg ' Thr Tyr Leu Wall Ala Glu Gly Leu Gly Ile Thr Ile Met 100 ALIGN! 105 110 Ile Leu Gly Ile Leu Wall Leu Leu Gly Leu Trp Met For Leu Met Gly 115 120 125 Wall Wall Gly Gly Leu Leu Wall Ala Gly Met Thr Ile Thr Thr Leu Phe 13 0 135 140 Phe Phe Ile His Asn Ala Arg Ser Wall Cys Gin Ser Ala Phe For Met 145 150 155 160 Ala Phe Trp Gly Trp Lys Ala Ser Gly 165

(2) Information for SEQ ID NO: 138:

(i) Sequence characteristics:

(A) Length: 487 amino acids (B) Type: amino acid (D) Topology: linear (ii) Molecule type: protein (iii) Hypothetical: YES (vi) Original source:

(A) Organism: Helicobacter pylori

271 (ix) Features:

(A) Name / key: misc_character

(B) ' Location: i ... 487 (xi) Popis sequence description: SEQ NO ID: 138: Met 1 - Ile Glu Trp Met Gin Asn 4 His Arg Lys Tyr Le Val Val Thr Ile 10 15 Trp Ile Ser  Thr Ile Ala Phe 20 May Ile Ala Ala Gly Me He Gly Trp Gly 25 30 Gin Tyr Ser 35 Phe Ser Leu Asp Ser Asp Ser Ala Ala Lys Val Gly Gin 40 Ile Lys Ile Ser Gin Glu 55 Leu Ala Gin Glu Tyr Arg Asp 65 Ala Tyr Ala Glu Ser Ile 69 For Asp Phe Lys Glu Leu Thr Glu Asp 75 80 Gin Ile Lys Ala Met His Leu Glu Lys Ser Ala Leu Asn Gin Ala Leu Leu Arg Asn 100 Phe Ala Leu Gly Leu Asp Leu 105 110 Thr Lys Gin Glu Val Ala Lys Glu Ile Arg. Lys Thr Asn Val Phe 120 · 125 Lys Asp Gly Val Phe Asp Glu Glu Leu Tyr Lys Asn Ser 145 His Tyr Arg Pro Lys His 150 Phe Glu Glu Ser Glu Arg Leu Leu 155 160 Ile Leu Gin Lys Ile Ser Ala Leu Phe Lys Thr Thr Thr Pro Leu 170 175 Glu Gin Ser Ser Leu 180 Trp Ala Lys Leu Gin Asp Ile Leu Ile Leu Asn For Asn Asp Val Lys Asle Glu Glu 200 205 Glu Met Lys Lys'Tyr Tyr Glu 215 Asn His Arg Lys Asp Thr 225 Ser Phe Lys Thr Arg Ser 230 Leu Tyr Phe Asp Ala Ser Thr Asp Leu Lys Glu Leu Glu 245 Glu Tyr Hisr Lys Asn Lys Val Ser 250 255 Tyr Leu Asp Lys Glu Gly Lys 260 Leu Gin Phu Lys Ser Glu Glu 265 270 Gin Val Lys His Asp Leu Asn Met Gin Lys Ala Asn Glu Lys Ala Leu Arg Ser Tyr 290 Ile Ala Leu Lys 295 Lys Gly Asn & Gin Asn Tyr Thr Thr 300 Gin 305 Asp Phe Glu Lys Asn Asn Ser Pro Tyr Thr Ala Glu Lys Leu Thr Ala Leu Lys Pro 325 Leu Glu Val Leu Lys Pro Glu Pro Phe 330 335 Lys Asp Gly Phe Ile Val Val 340 Gin Leu Val Ser Gin Ile Lys Asp Glu 345 350 Leu Gin Asn 355 Phe Asp Glu Ala Lys Ser Ala Leu Gin Glu Lys 370 Thr Leu Met Ala. .375 Leu Gin Thr Leu Glu Lys Leu 380 Lys 385 Asp Phe Lys Gly Lys Ser 390 Val Gly Tyr Val Ser Pro Asn Phe Gly 395 400

»·

272

Gly Thr Ile Ser Glu 405 Leu Asn Gin Thr Leu Phe Asn 420 Arg Gin Glu Lys Lys Wall Wall 435 Leu Tyr Gin Ile Thr 440 Ser Ala 450 Glu Glu Asn Gin Tyr 455 Met

Glu Glu 410 Ser Ala Lys Phe Ile 415 Asn Lys 425 Gly Phe Wall Thr Ile 430 Gly Asn Glu Gin Asn Phe Asn 445 His For Phe Gin Arg Leu Wall 460 Asn Asn Thr Lys

Thr Asp Phe Phe Asp Lys Ala LeU Ile Glu Glu Leu Lys Lys Arg Tyr 465 Lys Ile Wall Lys Tyr 485 470 Ile Gin 475 480

(2) Information for SEQ ID NO: 139:

(i) Sequence characteristics:

(A) Length: 142 amino acids (B) Type: amino acid (D) Topology: linear (ii) Molecule type: protein (iii) Hypothetical: YES (vi) Original source:

(A) Organism: Helicobacter pylori (ix)

(A) Name / Key: misc_character (B) Position: 1 ... 142 (xi) Sequence Description: SEQ ID NO: 139:

Met Lys Thr Asn Phe Tyr Lys Ile Lys Leu Leu Phe Ala Trp Cys Leu 1 5 10 15 Dec Ile Ile Gly Met Phe Asn Ala For Leu Asn Ala Asp Gin Asn Thr Asp 20 May 25 30 Ile Lys Asp Ile Ser For Glu Asp Met Ala Leu Asn Ser Wall Gly Leu 35 40 45 Wall Ser Arg Asp Gin Leu Lys Ile Glu Ile For Lys Glu Thr Leu Glu 50 55 60 Gin Lys Wall Ala Ile Leu Asn Asp Tyr Asn Asp Lys Asn Wall Asn Ile 65 70 75 80 Lys Phe Asp Asp Ile Ser Leu Gly Ser Phe Gin For Asn Asp Asn Leu 85 90 95 Gly Ile Asn Ala Met Trp Gly Ile Gin Asn Leu Leu Met Ser Gin Met 100 ALIGN! 105 110 Met Ser Asn Tyr Gly For Asn Asn Ser Phe Met Tyr Gly Tyr Ala For 115 120 125 Thr Tyr Ser Asp Ser Ser Phe Leu For For Ile Leu Gly Tyr 130 135 140

• · · ·

273

(2) Information for SEQ ID NO: 140:

(i). Sequence characteristics:

(A) Length: 208 amino acids (B) Type: amino acid. ’(D), Topology: Linear.

(ii) Molecule type: protein (iii) Hypothetical: YES (vi) Original source:

(A) Organism: Helicobacter pylori ------ (ix) Properties:

(A) Name / Key: misc_character (B) Location: 1 ... 208 (xi) Sequence Description: SEQ ID NO: 140:

Leu 1 Ile Asn Asn Asn 5 Asn Asn Asn Lys Lys 10 Leu Arg Gly Phe Phe 15 Dec Leu Lys Wall Leu Leu 20 May Ser Leu Wall Wall Phe 25 Ser Ser Tyr., Gly Ser 30 Ala Asn Asp Asp Lys 35 Glu Ala Lys Lys Glu 40 Ala Leu ¹ Glu Lys Glu 45 Lys Asn Thr For Asn 50 Gly Leu Wall· Tyr Thr 55 Asn Leu Asp Phe Asp 60 Ser Phe Lys Ala Thr 65 Ile Lys Asn Leu Lys 70 Asp Lys Lys wall Thr 75 Phe Lys Glu Wall Asn 80 For Asp Ile Ile Lys 85 Asp Glu Wall Phe Asp 90 Phe Wall Ile Wall Asn 95 Arg Wall Leu Lys Lys 100 ALIGN! Ile Lys Asp Leu Lys 105 His Tyr Asp For Wall 110 Ile Glu Lys Ile Phe 115 Asp Glu Lys Gly Lys 120 Glu Met Gly Leu Asn 125 Wall Glu Leu Gin Ile 130 Asn For Glu Wall Lys 135 Asp Phe Phe Thr Phe 140 Lys Ser Ile Ser Thr 145 Thr Asn Lys Gin Arg 150 Cys Phe Leu Ser Leu 155 His Gly Glu Thr Arg 160 Glu Ile Leu Cys Asp 165 Asp Lys Leu Tyr Asn 170 Wall Leu Leu Ala Wall 175 Phe Asn Ser Tyr Asp 180 For Asn Asp Leu Leu 185 Lys His Ile Ser Thr 190 Tle Glu Ser Leu Lys 195 Lys Ile Phe Tyr Thr 200 Ile Thr Cys Glu Ala 205 Wall Tyr Leu

(2) Information for SEQ ID NO: 141:

(i) Sequence characteristics:

274 ·· ···· (A) Length: 245 amino acids (B.) Type: amino acid (D) 'Topology: linear (iij ’Molecule type: protein (iii) Hypothetical: YES (vi) Original source:

(A) Organism: Helicobacter pylori (ix)

(A) Name / Key: misc_character (B) Location: 1 ... 245

(xi) Description sequence: SEQ ID NO: 141: Met 1 Ala Gly Thr Gin Ala Ile Tyr 4 Glu Ser 10 Ser Ser Ala Gly Phe Leu Ser Gin .Val Ser 20 May Ser Ile Ser Ser 25 Thr Ser Gly Val Ala Phe Ala Gly Ile Val Ala Gly Ala Met Thr Ala Ala Ile Pro Ile 45 Wall Val Gly Phe Thr Asn Pro Gin Met Thr Ala Ile Met Thr Gin Tyr 61 Asn 65 Gin Ser Ile Ala Glu Ala Val 69 Ser Wall For Met Lys Ala Ala Asn 75, 80 Gin Gin Tyr Asn Gin Leu Tyr Gin Gly Phe 90 Asn Asp Gin Ser Met Ala 94 Wall Gly Asn Asn Ile Leu Asn Ile Ser 105 Lys Leu Thr Gly Glu Phe Asn 110 Ala Gin Gly Asn Thr Gin Ser Ala · 120 Gin Ile Ser Ala Val Asn Ser- Gin 125 Ile Ala Ser Ile 130 Leu Ala Ser Asn-Thr 135 Thr Pro Lys Asn Pro Ser Ala 140 Ile 145 Glu Ala Tyr Ala Thr Asn Gin ISO Ile Ala Val Pro Ser Val Pro Thr 155 160 Thr Val Glu Met Met Ser Gly Ile Leu Gly 170 Asn Ile Thr Ser Ala Ala 174 For Lys Tyr Al 180 Leu Ala Leu Gin Glu 185 Gin Leu Arg Gin Ala Ser 190 Asn Ser Ser Met 195 Asn Asp Thr Ala 200 Asp Ser Leu Asp Ser Cys Thr Ala 205 Leu Gly Ala Leu Val Gly Ser Ser 215 Lys Wall Phe Phe Ser Cys Met Gin Ile 225 Ser Met Thr For Met Ser Val 230 Ser Met Pro Thr Val Met Pro Asn 235 240

Thr Ser Gly Cys His 245 (2) Information for SEQ ID NO: 142:

····

275 (i) Sequence characteristics:

(A) Length: 367 amino acids (B) Type: amino acid (D) Topology: linear (ii) _; Molecule type: protein (iii) Hypothetical: YES (vi) Original source:

(A) Organism: Helicobacter pylori

----- (ix) Features:

(A) Name / Key: misc_charakter (B) Location: 1 ... 367 (xi) Description of Sequence: SEQ ID NO: 142:

1 5 10 15 Dec Lys Met Glu Asn 20 May Phe Lys Leu Ile Asn 25 Phe Phe Thr Gly Gin 30 Asn Asp Ala Gly Lys 35 Thr Asn Leu Leu Glu 40 Ala. Leu Tyr Thr Asn 45 Thr Gly Leu Cys Asp 50 For Thr Ala Asn Gin ⁵⁵ Wall Ser. Leu For For 60 Glu His Ala Wall Asn 65 Ile Ser Glu Phe Arg 70 Lys Ue Lys Leu Asp 75 Ala Asp Asn Leu Lys 80 Thr Phe Phe Tyr Gin 85 Gly Asn Thr Ala Asn 90 For Ue Ser Ue Arg 95 Thr Glu Phe Glu His 100 ALIGN! Ala Thr Ile For Leu 105 Thr Ile Gin Tyr For 110 Thr Gin Thr Ser Tyr 115 Ser Lys Asp Ue Asn 120 Leu Asn Ser Asp Asp 125 Ala His Met Thr Asn 130 Leu Ile Asn Thr Thr 135 Ue Thr Lys For Gin 140 Leu Gin Phe Ser Tyr 145 Asn For Ser Leu Ser ISO For Met Thr Met Thr 155 Tyr Glu Phe Glu Arg 160 Gin Asn Leu Gly Leu 165 Ue His Ser Asn Leu 170 Asp Lys Ile Ala Gin 175 Thr Tyr Lys Glu. Asn 180 Ala Met Phe Ile For 185 Ue Glu Leu Ser Ile 190 Wall Asn Ser Leu Lys 195 Ala Leu Glu Asn Leu 200 Gin Leu Ala Ser Lys 205 Glu Lys Glu Leu Ile 210 Glu Ile Leu Gin Cys 215 Phe Asn For Asn Ile 220 Leu Asn Ala Asn Thr 225 Ile Arg Lys Ser Wall 230 Tyr Ile Gin Ile Lys 235 Asp Glu Asn Thr For 240 Leu Glu Glu Ser For 245 Lys Arg Leu Leu Asn 250 Leu Phe Gly Trp Gly 255 Phe Ile Lys Phe Phe 260 Ile Met Wall Ser Ile 265 Leu Ile Asp Asn Arg 270 Wall Lys Tyr Leu Phe 275 Ile Asp Glu Ile Glu 280 Ser Gly Leu His His 285 Thr Lys Met Gin Glu 290 Phe Leu Lys Ala ' Leu * ²⁹⁵ Phe Lys Leu Ala Gin 300 Lys Leu Gin Ile Gin 305 Ile Phe Ala Thr Thr 310 His Asn Lys Glu Phe 315 Leu Leu Asn Ala Ile 320

• 99999999 99 • 9 9 9 9

276 9 9 • 9 <· 9 9 9 9 • 9 9 Asn Thr ile Ser Asp Asn Glu Thr Gly Wall Phe Lys Asp Ile ' 'Ala Leu 325 330 335 Phe Glu Leu Glu Lys Glu Ser Ala Ser Gly Phe Ile Arg His Ser Tyr 340 345 350 Ser Met Leu Glu Lys Ala Leu Tyr Arg Gly Met Glu Wall Arg Gly 355 360 365 ) Information for SEQ ID NO: 143

(i) Sequence characteristics:

(A) Length: 409 amino acids (B) .Type: amino acid (D) Topology: linear (ii) Molecule type: protein (iii) Hypothetical: YES (vi) Original source:

---------- (A) Organism: Helicobacter pylori (ix) Properties:

(A) Name / Key: misc_character (B) Location: 1 ... 409

(xi) Description sequence: SEQ ID NO: 143: Met Ser Leu 1 Ile Arg Val Asn Gly Glu Ala Phe Lys Leu Ser Leu Glu 10 Ser Leu Glu Asp Glu 20 Phe Glu Thr 25 Lys Glu Thr Leu Glu Thr Leu 35 Ile Lys Gin Thr Ser 40 Wall Val Leu Leu Ala Ala Gly Glu 45 Ser Lys Arg Phe Ser Arg Ala 55 Ile Lys Lys Gin Trp Leu Arg His Thr Pro Leu Trp Leu Ser Wall Tyr Glu Ser Phe Lys Glu Ala Leu 75 Asp Phe Lys Glu Val Ile Leu Wall Wall Ser Glu Leu Asp Tyr Val Tyr 90 Ile Gin Arg His Tyr Pro 100 Lys Ile Lys 105 Leu Val Lys Gly Ala Ser 110 Arg Gin Glu Ser Val Arg Asn Ala 120 Leu. Lys Val Ile Asp Ser Thr Tyr 128 Thr Ile Thr 130 Ser Asp Val Ala 135 Arg Gly Leu Ala Asn Met by Glu Ala Leu 140 Lys Ser Leu Phe Leu Thr 150 Leu Gin Gin Thr Ser His Tyr Cys Ile Ala 155 161 For Tyr Leu For Cys Tyr 165 Asp Thr Ala Ile Tyr Tyr Asn Glu Ala Leu Asp Arg Glu Ala Ile Lys Leu Ile Gin 185 Thr Pro Gin Leu Lys Thr Leu 195 Gin Ser Ala Leu Asn 200 Gin Gly Gly Phe Lys Ser Ala Ile Leu Gin Ala Phe 215 For Asn Ser Val Ser Tyr Ile Glu Gly 220 Ser Lys Asp 225 Leu His Lys Leu Thr Thr Ser Gly Asp Leu Lys Phe Phe 235 239 Thr Pro Phe Phe Asn Pro 245 Ala Lys Asp Thr Phe Ile Gly Met Gly Phe 250 Asp Thr His Ala Phe Ile 260 Lys Asp Lys 265 For Met Val Leu Gly Gly Val 270 Val Leu Asp 275 Cys Glu Phe Gly Leu 280 Lys. Ala His Ser Asp (Original Mix) Gly Asp Ala 285 Leu Leu His 290 Ala Val Ile Asp 295 Ala Ile Leu Gly Ala Ile Lys Gly Gly 300

277

Asp Ile Gly Glu Trp Phe For Asp Asn Asp For 305 310 315 Ser Ser Lys Glu Leu Leu Lys Ile Wall Leu Asp 325 330 Gly Phe Glu Leu Leu Glu Met Gly Ala Thr Ile 340 345 Lys Ile Thr For Tyr Lys For Ala Ile Leu Glu 355 360 Leu Gly Leu Glu · Lys Ser Gin Ile Ser Leu Lys 370 375 Lys Met Gly. Phe Ile Gly  Lys Gin Glu Gly Leu 3Θ5 390 395 Wall Ser Met Arg Tyr Lys Gin Lys Leu

405

• · · ·· • • · • · ···· » • - Φ · · · • « '· · • 'Φ' · · · · · · · • • · • · · ··· · • · · '·· • · · · · Lys Tyr Lys Asn Ala 320 Phe Ser Gin Ser 335 Ile Phe Ser Glu 350 Ile For Asn Leu 365 Ser Gin Leu Ala 380 Thr Thr Met Glu Leu Wall Gin Ala His

400 (2) Information for SEQ ID NO: 144:

(i) Sequence characteristics:

(A) Length: 270 amino acids (B) Type: amino acid (D) Topology: linear (ii) Molecule type: protein.

(iii) Hypothetical: YES (vi) Original Source:

(A) Organism: Helicobacter pylori (ix)

(A) Name / Key: misc_character (B) Location: 1 ... 270 (xi) Sequence Description: SEQ ID NO: 144:

Met Lys Lys Phe Wall Ala Leu Gly Leu Leu Ser Ala Wall Leu Ser Ser 1 5 10 15 Dec Ser Leu Leu Ala Glu Gly Asp Gly Wall Tyr Ile Gly Thr Asn Tyr Gin 20 May 25 30 Leu Gly Gin Ala Arg Leu Asn Ser Asn Ile Tyr Asn Thr Gly Asp Cys 35 40 - 45 Thr Gly Ser Wall Wall Gly Cys For For Gly Leu Thr Ala Asn Lys His 50 55 60 Asn For Gly Gly Thr Asn Ile Asn Trp His Ser Lys Tyr Ala Asn Gly 65 70 75 80 Ala Leu Asn Gly Phe Gly Leu Asn Wall Gly Tyr Lys Lys Phe Phe Gin 85 90 95 Phe Lys Ser Leu Asp Met Thr Ser Lys Trp Phe Gly Phe Arg Wall Tyr 100 ALIGN! 105 110 Gly Leu Phe Asp Tyr Gly His Ala Asp Leu Gly Lys Gin Wall Tyr Ala 115 120 125 For Asn Lys Ile Gin Leu Asp Met Wall Ser Trp Gly Val Gly Ser Asp 130 135 140

• 0 900 «

278 • · ·

0 0 »0 0 0 0

Wall

Lys

225

Lys

Lys

Ala 210 Phe Gin wall Trp Leu 215 Asn Phe His Asn Gly Wall Glu 230 Phe Gly Wall Phe Leu Ser Ala 245 .Giy · For Asn Ala Arg Asp Tyr 260 Ser Leu. Tyr Leu Gly 265

Gly Wall Arg Ala Asn ile Tyr 220 Arg wall For Leu Leu Ile Asn 235 240 Thr Asn Leu Tyr Tyr His Leu 250 255 Tyr Asn Tyr Thr Phe 270

(2) Information for SEQ ID NO: 145:

(i) Sequence characteristics:

(A) Length: 438 amino acids (B) Type: amino acid (D) Topology: linear (ii) Molecule type: protein (iii) Hypothetical: YES (vi) Original source:

(A) Organism: Helicobacter pylori (ix)

(A) Name / Key: misc_charakter (B) Location: 1 ... 438 (xi) Sequence Description: SEQ ID NO: 145:

Met 1 Ala Tyr Lys For 5 Asn Lys Lys Lys Leu Lys Glu Leu Arg Glu 15 Dec Gin For Asn Leu Phe 20 May Ser Ile Leu Asp Lys 25 Gly Asp Wall Ala Thr 30 Asn Asn For Wall Glu 35 Glu Ser Asp Lys Ala 40 Asn Lys Ile Gin Glu 45 For Leu For Tyr Wall 50 Wall Lys Thr Gin Ile 55 Asn Lys Ala Ser Met 60 Ile Ser Arg Asp For 65 Ile Glu Trp Ala Lys 70 Tyr Leu Ser Phe Glu 75 Lys Arg Wall Tyr Lys 80 Asp Asn Ser Lys Glu 85 Asp Wall Asn Phe Phe Ala Asn Gly Glu Ile 95 Lys

279

• ·· ·· ···· ·, · ·· • · ♦ · · • · • · · · • · · · • · • ··· ··· • · · • · • · • ·· · ··· ·· · ·· ··

Glu Ser Ser Arg Val Glu Glu Ala Asn Lys Glu Gly Phe Arg Arg 100 ALIGN! 105 110 Ile Thr Lys Arg Tyr Asp Leu Ile Asp Arg Asn Arg Arg Asn Arg 115 120 125 Glu Phe Ile Lys Glu Ile Leu Thr His Thr Asn Ser Leu 130 135 140 Lys Glu Leu Lys Glu Gin Leu Glu Ile Gin Leu Thr His His Asn 145 150 155 160 Glu Thr'His Lys Lys Ala Leu Glu Asn Gly Asn Glu 165 170 175 Asp-His Leu Lys Asp Ile Tyr Gin Glu Val Glu Arg Thr Lys Asp 180 185 190 Gly Gly. Leu Wall Arg Glu Ile Ile-Pro Ser Ile Ser.Ser Ala Glu Tyr  195 200 205 Phe Lys Tyr Asn Lys'Leu Pro Phe Glu Ser: lle Asn.Asn Glu..Asn 210 215 220 Lys Leu Thr Asn Thr Asn Asp Asn Glu Glu Val Lys Leu Glu Phe 225 ----- 230 235_240 Glu Leu Ala Lys Glu Val His lele Leu Gle Gin Gle Leu Leu 245 250 255 Ser Ala Thr Asn Tyr Tyr Ser Trp Ile Asp Lys Asp Asp Asn Ala Asn 260 265 270 Phe Ala Trp Lys Met His Arg - Leu Ile Asn Lys Asn Lys Leu Lys Glu 275 280 285 Asn His Leu Ser Ala Asn Asn Lys Gle Phe Phe Phe 290 295 300 Asn Gly Ser Gle Trp Thr Lys Glu Glu Ser Ala Ile 305 310 315 320 Gin Glu Asn Arg Asp Tyr Ser Ser Ala Leu Leu Ser Leu Glu 325 330 335 Glu Ile Ala Gin Ala Lys Gle Leu Gin Lys Tyr Glu Ser Val 340 345 350 Tyr Val Asn Gly Asp Gly Asn Lys Arg Glu Ile Lys Pro Phe, Lys Glu 355 360 365 Ile Leu Arg Asp Thr Asn Phn Glu Lys Ala Tyr 370 375 380 Asp Lys Leu Wall Ser Leu Ser Ala Ala Ile Ile Gin 385 390 395 400 Gly Asn Glu Arg For Asn Ser Ser Ala Asn Asn Asn Asn For Ile Lys 405 410 415 Asn Thr Ile Glu Thr Asn Thr Ser Asn Asn Asle Asle Asn Asp 420 425 430 Asn Ile Ile Ile Gin Ile

435 (2) Information for SEQ ID NO: 146:

(i) Sequence characteristics:

(A) Length: 215 amino acids (B) Type: amino acid ·· ·· »·

280 · 99 • 9

9 9

9 9-9 9

9 (D) Topology: lineami (ii) Molecule type: protein (iii) 'Hypothetical: YES (vi), Original source:

(A) Organism: Helicobacter pylori (ix)

(A) Name / key: misc_character

B) Location: 1.. . 215 (xi) Sequence description: SEQ ID

Met 1 Gin Ala Leu Lys 5 Ser Leu Leu Gly Gly Tyr 20 May Leu Met His Ile Ile Gly Gly 35 Leu Lys Phe Wall For 40 Phe Wall 50 Ala Asn Ser For Phe 55 Phe · For 55 Ala Tyr Lys Gin His 70 Lys Met Glu Met Gin Asp Asn 85 For Lys Ile Glu Asn Arg Thr 100 ALIGN! Tyr Leu Wall Ala Ile Leu Gly 115 Ile Leu Wall Leu Leu 120 Wall Wall 130 Gly Gly Leu Leu Wall 135 Ala Phe 145 Leu Phe Thr Thr For 150 Glu Wall Leu Ser Gly Ala Gly 165 Arg Leu Wall Gly Gly Leu Phe 180 Wall Ala Gly Phe Lys Gly Phe 195 Cys Leu Met Asp Arg 200 Cys Ser 210 Ser Gly Cys Cys Ser 215

NO: 146:

Glu Val Ile Thr Lys Leu Gin Asn 10

Ala Ile Phe Ile ^Phle He Trp 25 30

Tyr Glu Ala Glu Gly 45 Ile Ala For Ser Phe Met Tyr 60 Lys Phe Glu Lys. Ser Glu Ser 75. Gin Ser Met Gin Glu 80 Wall Glu 90 Asn Lys Glu Trp His. 95. Lys Glu 105 Gly Leu Gly Ile Thr 110 Ile Met Gly Leu Trp Met For 125 Leu Met Gly Gly Met Thr Ile 140 Thr Thr Leu Ser Phe Wall Asn 155 Gin His Phe For Trp 160 Wall Lys 170 Asp Leu Ala Leu Phe 175 Ala Asp 185 Ala Lys Arg Tyr Leu 190 Glu Gly Ser Ser Wall Gly Ile 205 Lys Thr Lys

(2) Information for SEQ ID NO:

147:

TAG (i) Sequence characteristics:

(A) Length: 20 pairs of flanks

281 · ♦ ♦ «« «« «t t t t t t t t t t t t t t t t t t t t t t · (Β) Type: nucleic acid (C). String: double.

(D) Topology: circular, _k (ii) Molecule type: DNA (genomic) (iii); Hypothetical: NO (iv) Antisense: NO (vi) Original Source:

(A) Organism: Helicobacter pylori (ix)

(A) Name / Key: misc_character (B) Location: 1 ... 20 (xi) Sequence Description: SEQ ID NO: 147:

TATACCATGG TGGGCGCTAA (2) Information for SEQ ID NO: 148:

(i) Sequence characteristics:

(A) Length: 23 pairs (B) Type: nucleic acid (C) String: double (D) Topology: circular Y (ii) Molecule type: DNA (genomic) (iii) Hypothetical: NO (iv) Antisense: NO (vi) Original source:

(A) Organism: Helicobacter pylori (ix)

(A) Name / Key: misc_charakter (B) Location: 1 ... 23 (xi) Sequence Description: SEQ ID NO: 148:

ATGAATTCGA GTAAGGATTT TTG ²³ (2) Information for SEQ ID NO: 149:

(I) Sequence characteristics:

(A) Length: 22 pairs (B) Type: nucleic acid (C) String: double (D). Topology: circular (ii) Molecule type: DNA (genomic) (iii) Hypothetical: NO (iv) Antisense: NO (vi) Original source:

(A) Organism: Helicobacter pylori (ix)

(A) Name / Key: misc_charakter (B) Location: 1 ... 22 (xi) Sequence Description: SEQ ID NO: 149:

TTAACCATGG TGAAAAGCGA TA (2) Information for SEQ ID NO: 150:

(i) Sequence characteristics:

(A) Length: 23 pairs (B) Type: nucleic acid (C) String: double (D) Topology: circular (ii) Molecule type: DNA (genomic) (iii) Hypothetical: NO (iv) Antisense: NO ( (vi) Original source:

(A) Organism: Helicobacter pylori (ix)

(A) Name / Key: misc_charakter (B) Location: 1 ... 23 (xi) Sequence Description: SEQ ID NO: 150:

TAGAATTCGC ATAACGATCA ATC • 0

• · • • · • 0 0 0 00 00 0 0 · • • * · • 0 0 0 0 • • • • · • 0 0 0 0 0 0 0 0 • 0 • • 0 0 0 • · · · · • · • · 0 0 0 0 0

(2) Information for SEQ ID NO: 151:.

(i) Sequence characteristics:

(A) Length: 22 pairs throws.

(B) Type: 'nucleic acid' (C) Chain: double (D) Topology: circular (ii) Molecule type: DNA (genomic) (iii) Hypothetical: 'NO (iv) Antisense: NO ------ (vi) Original source:

(A) Organism: Helicobacter pylori (ix)

(A) Name / Key: misc_charakter (B) Location: 1 ... 22 (xi) Sequence Description: SEQ ID NO: 151:

ATATCCATGG TGAGTTTGAT GA ‘22 (2) Information for SEQ ID NO: 152:

(i) Sequence characteristics:

(A) Length: 25 pairs (B) Type: nucleic acid (C) String: double (D) Topology: circular (ii) Molecule type: DNA (genomic) (iii) Hypothetical: NO (iv) Antisense: NO ( (vi) Original source:

(A) Organism: Helicobacter pylori (ix)

(A) Name / Key: misc_charakter (B) Location: 1 ... 25 (xi) Sequence Description: SEQ ID NO: 152:

ATGAATTCAA TTTTTTATTT TGCCA

AND.

'TO

4

284

4 (2) Information for SEQ ID NO: 153:

(i) Sequence characteristics:

(A) Length: 21 pairs (b) Type: nucleic acid (C) String: double (D) Topology: circular (ii) Typ. molecules: DNA (genomic) (iii) Hypothetical: NO (iv) Antisense: NO (vi) Original source:

(A) Organism: Helicobacter pylori (ix)

(A) Name / Key: misc_character (B) Location: 1 ... 21 (xi) Sequence Description: SEQ ID NO: 153: AATTCCATGG TGGGGGCTAT G (2) Information for SEQ ID NO: 154:

(i) Sequence characteristics:

(A) Length: 23 pairs (B) Type: nucleic acid (C) String: double (D) Topology: circular (ii) Molecule type: DNA (genomic) (iii) Hypothetical: NO (iv) Antisense: NO ( (vi) Original source:

(A) Organism: Helicobacter pylori (ix)

(A) Name / Key: misc_charakter (B) Location: 1 ... 23 (xi) Sequence Description: SEQ ID NO: 154:

ATGAATTCTC GATAGCCftAA ATC

285 (2) Information for SEQ ID NO: 155:

(i) Sequence characteristics:

(A) Length: 25 pairs (B) Type: nucleic acid (C). String: double. .

(D) Topology: circular (ii) Type of molecule: DNA (genomic) (iii) .Hypothetic: NO (iv) Antisense: NO (vi) Original source:

(A) Organism: Helicobacter pylori (ix)

(A) Name / Key: misc_character (B) Location: 1 ... 25 (xi) Sequence Description: SEQ ID NO: 155:

aattccatgg tgcataactt ccatt (2) Information for SEQ ID NO: 156 .: ^- '' (i) Sequence characteristics:

(A) Length: 25 pairs (B) Type: nucleic acid (C) String: double (D) Topology: circular (ii) Molecule type: DNA (genomic) (iii) Hypothetical: NO (iv) Antisense: NO ( (vi) Original source:

(A) Organism: Helicobacter pylori (ix)

(A) Name / Key: misc_charakter (B) Location: 1 ... 25 (xi) Sequence Description-.SEQ ID NO: 156:

AAGAATTCTC TAGCATCCAA ATGGA

286

(2) Information forSEQ ID NO: 157:

(i) Sequence characteristics:

(A) Length: 24 pairs (B) Type: nucleic acid (C) String: double.

, (D) Topology: circular (ii) Molecule type: DNA (genomic) (iii) Hypothetical: NO (iv) Antisense: NO ---- (vi) Original source:

(A) Organism: Helicobacter pylori (ix)

(A) Name / Key: misc_charakter (B) Location: 1 ... 24 (xi) Sequence Description: SEQ ID NO: 157:

ATTTCCATGG TCATGTCTCA TATT (2) Information for SEQ ID NO: 158:

(i) Sequence characteristics:

(A) Length: 23 pairs (B) Type: nucleic acid (C) String: double (D) Topology: circular (ii) Molecule type: DNA (genomic) (iii) Hypothetical: NO (iv) Antisense: NO ( (vi) Original source:

(A) Organism: Helicobacter pylori (ix)

(A) Name / Key: misc_charakter (B) Location: 1 ... 23 (xi) Sequence Description: SEQ ID NO: 158:

ATGAATTCCA TCTTTTATTC CAC

287

(2) Information for SEQ ID NO: 159:

(i) 'Sequence characteristics:

(A) Length: 27 pairs.

(B) Type: nucleic acid (C) String: double (D) Topology: circular. · (Ii) Molecule type: DNA (genomic) (iii) Hypothetical: NO

------------- (- iv) Antisense: NO (vi) Original Source:

(A) Organism: Helicobacter pylori (ix)

(A) Name / Key: misc_charakter (B) Location: 1 ... 27 (xi) Sequence Description: SEQ ID NO: 159:

AACCATGGTG ATTTTAAGCA TTGAAAG. ´ 27 (2) Information for SEQ ID NO: 160:

(i) Sequence characteristics:

(A) Length: 28 pairs (B) Type: nucleic acid (C) String: double (D) Topology: circular (ii) Molecule type: DNA (genomic) (iii) Hypothetical: NO (iv) Antisense: NO ( (vi) Original source:

(A) Organism: Helicobacter pylori (ix)

(A) Name / Key: misc_charakter (B) Location: 1 ... 28 (xi) Sequence Description: SEQ ID NO: 160:

aagaattcca ctcaaaattt TTTAACAG

288

(2) Information for SEQ ID NO: 161:

(i). Sequence characteristics:

• (A) Length: 25 bp (B) Type: nucleic acid (C) String: double ‘. (D / '. Topology: circular (ii) Molecule type: DNA (genomic) (iii) Hypothetical: NO (iv) Antisense: NO (vi) Original source:

(A) Organism: Helicobacter pylori (ix)

(A) Name / Key: misc_character (B) Location: 1 ... 25 (xi) Sequence Description: SEQ ID NO: 161: GATCATCCAT ATGTTATCTT CTAAT (2) Information for SEQ ID NO: 162 :. (i) Sequence characteristics:

(A) Length: 23 pairs (B) Type: nucleic acid (C) String: double (D) Topology: circular (ii) Molecule type: DNA (genomic) (iii) Hypothetical: NO (iv) Antisense: NO ( (vi) Original source:

(A) Organism: Helicobacter pylori (ix)

(A) Name / Key: misc_character (B) Location: 1 ... 23 (xi) Sequence Description: SEQ ID NO: 162:

TGAATTCAAC CATTTTAACC CTG

(2) Information for SEQ ID NO: 163:

(i) Sequence characteristics:

(A) * Length: 27 pairs (B) Type: nucleic acid (C) String: double (D) Topology: circular (ii) Molecule type: DNA (genomic) (iii) Hypothetical: NO (iv) Antisense: NO .....

(vi) Original source:

(A) Organism: Helicobacter pylori (ix)

(A) Name / Key: misc_character (B) Location: 1 ... 27 (xi) Sequence Description: SEQ ID NO: 163: TATACCATGG TGAAATTTTT TCTTTTA (2) Information for SEQ ID NO: 164:

(i) Sequence characteristics:

(A) Length: 25 pairs (B) Type: nucleic acid (C) String: double (D) Topology: circular (ii) Molecule type: DNA (genomic) (iii) Hypothetical: NO (iv) Antisense: NO ( (vi) Original source:

(A) Organism: Helicobacter pylori (ix)

(A) Name / Key: misc_character (B) Location: 1 ... 25 (xi) Sequence Description: SEQ ID NO: 164: AGAATTCAAT TGCGTCTTGT AAAAG • 4 ····

290 (2) Information for SEQ ID NO: 165:

(i) Sequence characteristics:

(A). Length: 24 pairs (B) Type: nucleic acid (C) String: double (D) Topology: circular (ii) Molecule type: DNA (genomic) (iii) Hypothetical: NO (iv) Antisense: NO (vi) Original source:

(A) Organism: Helicobacter pylori (ix)

(A) Name / Key: misc_character (B) Location: 1 ... 24 (xi) Sequence Description: SEQ ID NO: 165: TATACCATGG TGATGGACAA ACTC (2) Information for SEQ ID NO: 166:

(i) Sequence characteristics:

(A) Length: 23 pairs (B) Type: nucleic acid (C) String: double (D) Topology: circular (ii) Molecule type: DNA (genomic) (iii) Hypothetical: NO (iv) Antisense: NO ( (vi) Original source:

(A) Organism: Helicobacter pylori (ix)

(A) Name / Key: misc_charakter (B) Location: 1 ... 23 (xi) Sequence Description: SEQ ID NO: 166:

ATGAATTCCC ACTTGGGGCG ATA

291

• BB «· * • B «·· <* • · • · »· B • 0 • B • «B BBB • · • • B (B) ·· ···· • · · Λ ·

(2) Information for SEQ ID NO: 167:

(i) Sequence characteristics:

(A) Length: 25 pairs (B) Type: nucleic acid (C) String: double (D) Topology: circular (ii) Molecule type: DNA (genomic) (iii) Hypothetical: NO (iv) Antisense: NO ( (vi) Original source:

(A) Organism: Helicobacter pylori (ix)

(A) Name / Key: misc_character (B) Location: 1 ... 25 (xi) Sequence Description: SEQ ID NO: 167: TTATGGATCC AAACCAATTA AAACT (2) Information for SEQ ID NO: 168:

(i) Sequence characteristics:

(A) Length: 23 pairs (B) Type: nucleic acid (C) String: double (D) Topology: circular (ii) Molecule type: DNA (genomic) (iii) Hypothetical: NO (iv) Antisense: NO ( (vi) Original source:

(A) Organism: Helicobacter pylori (ix)

(A) Name / Key: misc_charakter (B) Location: 1 ... 23 (xi) Sequence Description: SEQ ID NO: 168:

TATCTCGAGT TATAGAGAAG GGC

292

(2) Information for SEQ ID NO: 169:

(i) Sequence Characteristics:

(A) Length: 22 pairs (B) Type: nucleic acid, (C) String: double (D) Topology: circular (ii) Molecule type: DNA (genomic) (iii) Hypothetical: NO (iv) Antisense: NO (vi) Original source:

(A) Organism: Helicobacter pylori (ix)

(A) Name / Key: misc_charakter (B) Location: 1 ... 22 (xi) Sequence Description: SEQ ID NO: 169:

TTAACCATGG TGAAAAGCGA TA ²² (2) Information for SEQ ID NO: 170:

(i) Sequence characteristics:

(A) Length: 24 pairs (B) Type: nucleic acid (C) String: double (D) Topology: circular (ii) Molecule type: DNA (genomic) (iii) Hypothetical: NO (iv) Antisense: NO ( (vi) Original source:

(A) Organism: Helicobacter pylori (ix)

(A) Name / Key: misc_charakter (B) Location: 1 ... 24 (xi) Sequence Description: SEQ ID NO: 170:

TAGAATTCGC CTCTAAAACT TTAG

(2) Information for SEQ ID NO: 171:

(i) Sequence characteristics:

(A) Length: 22 pairs (B) Type: nucleic acid (C). String: “double (D). Topology: circular (ii) Molecule type: DNA (genomic) (iii) Hypothetical: NO (iv) Antisense: NO (vi) Original source:

(A) Organism: Helicobacter pylori (ix)

(A) Name / Key: misc_character (B) Location: 1 ... 22 (xi) Sequence Description: SEQ ID NO: 171: TTAACCATGG TGAAAAGCGA TA (2) Information for SEQ ID NO: 172:

(i) Sequence characteristics:

(A) Length: 23 pairs (B) Type: nucleic acid (C) String: double (D) Topology: circular (ii) Molecule type: DNA (genomic) (iii) Hypothetical: NO (iv) Antisense: NO ( (vi) Original source:

(A) Organism: Helicobacter pylori (ix)

(A) Name / Key: misc_charakter (B) Location: 1 ... 23 (xi) Sequence Description: SEQ ID NO: 172:

TAGAATTCGC ATAACGATCA ATC

294 (2) Information for SEQ ID NO: 173:

(i) Sequence characteristics:

(A) Length: .22 pairs of baffles (B) Type: nucleic acid (C) String: double (D) Topology: circular. (ii) Type. molecules: DNA (genomic) (iii) Hypothetical: NO (iv) Antisense: NO (vi) Original source:

(A) Organism: Helicobacter pylori (ix)

(A) Name / Key: misc_charakter (B) Location: 1. ..22 (xi) Sequence Description: SEQ ID NO: 173:

ATATCCATGG TGAGTTTGAT GA (2) Information for SEQ ID NO: 174:

(i) Sequence characteristics:

(A) Length: 25 pairs (B) Type: nucleic acid (C) String: double (D) Topology: circular (ii) Molecule type: DNA (genomic) (iii) Hypothetical: NO (iv) Antisense: NO ( (vi) Original source:

(A) Organism: Helicobacter pylori (ix)

(A) Name / Key: misc_charakter (B) Location: 1 ... 25 (xi) Sequence Description: SEQ ID NO: 174:

ATGAATTCAA TTTTTTATTT TGCCA

295

(2) Information for SEQ ID NO: 175 ,:

(i) Sequence characteristics:

(A) Length: 23 pairs (B) Type: nucleic acid (C). String: double (D) Topology: circular (ii) Type-molecule: DNA (genomic) (iii) Hypothetical: NO (iv) Antisense: NO (vi) Original Source:

(A) Organism: Helicobacter pylori (ix)

(A) Name / Key: misc_charakter (B) Location: 1 ... 23 (xi) Sequence Description: SEQ ID NO: 175:

AATTCCATGG CTATCCAAAT CCG (2) Information for SEQ ID NO: 176:

(i) Sequence characteristics:

(A) Length: 25 pairs (B) Type: nucleic acid (C) String: double (D) Topology: circular (ii) Molecule type: DNA (genomic) (iii) Hypothetical: NO (iv) Antisense: NO ( (vi) Original source:

(A) Organism: Helicobacter pylori (ix)

(A) Name / Key: misc_charakter (B) Location: 1 ... 25 (xi) Sequence Description: SEQ ID NO: 176:

ATGAATTCGC CAAAATCGTA GTATT

296 (2) Information for SEQ ID NO: 177:

(i) Sequence characteristics:

(A) Length: 24 bp (B) Type: nucleic acid (C) String: double (D) ‘Topology: circular (ii). Molecule Type: DNA (genomic) (iii) Hypothetical: NO (iv) Antisense: NO ---- (vi) Original Source:

(A) Organism: Helicobacter pylori (ix)

(A) Name / Key: misc_charakter (B) Location: 1 ... 24 (xi) Sequence Description: SEQ ID NO: 177:

GATACCATGG AATTTATGAA AAAG ²⁴ (2) Information for SEQ ID NO: 178:

(i) Sequence characteristics:

(A) Length: 25 pairs (B) Type: nucleic acid (C) String: double (D) Topology: circular (ii) Molecule type: DNA (genomic) (iii) Hypothetical: NO (iv) Antisense: NO ( (vi) Original source:

(A) Organism: Helicobacter pylori (ix)

(A) Name / Key: misc_character (B) Location: 1 ... 25 (xi) Sequence Description: SEQ ID NO: 178:

TGAATTCGAA AAAGTGTAGT TATAC

297

(2) Information for SEQ ID NO: 179:

(i) Sequence characteristics:

(A) Length: 19 bp (B) Type :, nucleic acid (C) String: "double (D) -Topology: circular (ii) 'Molecule type: DNA (genomic) (iii) Hypothetical: NO (iv) ) Antisense: NO (vi) Original Source:

(A) Organism: Helicobacter pylori (ix)

(A) Name / Key: misc_charakter (B) Location: 1 ... 19 (xi) Sequence Description: SEQ ID NO: 179:

CCCTTCATTT TAGAAATCG (2) Information for SEQ ID NO: 180:

(i) Sequence characteristics:

(A) Length: 20 pairs (B) Type: nucleic acid (C) String: double (D) Topology: circular (ii) Molecule type: DNA (genomic) (iii) Hypothetical: NO (iv) Antisense: NO ( (vi) Original source:

(A) Organism: Helicobacter pylori (ix)

(A) Name / Key: misc_character (B) Location: 1 ... 20 (xi) Sequence Description: SEQ ID NO: 180:

ATTTCAACCA ATTCAATGCG

298 • (2). Information for SEQ ID NO: 181:

(i) .Sequence characteristics:

(A) Length: 20 pairs. (B) Type: nucleic acid (C). String: double (D) Topology: circular (ii) Molecule type: DNA .. (genomic) (iii) Hypothetical: NO (iv) Antisense: NO (vi) Original source:

. (A) Organism: Helicobacter pylori (ix)

(A) Name / Key: misc_Character (B) Location: 1 ... 20 (xi) Sequence Description: SEQ ID NO: 181: GCCCCTTTTG ATTTGAAGCT (2) Information for SEQ ID NO: 182:

(i) Sequence characteristics:

(A) Length: 22 pairs (B) Type: nucleic acid (C) String: double (D) Topology: circular (ii) Molecule type: DNA (genomic) (iii) Hypothetical: NO (iv) Antisense: NO ( (vi) Original source:

(A) Organism: Helicobacter pylori (ix)

(A) Name / Key: misc_charakter (B) Location: 1 ... 22 (xi) Sequence Description: SEQ ID NO: 182:

TCGCTCCAAG ATACCAAGAA GT

299 (2) Information for SEQ ID NO: 183:

(i) Sequence characteristics:

(A) Length: 22 pairs · (B) Type: nucleic acid (C), String: double (D) Topology: circular (ii) Molecule type: DNA (genomic) (iii) Hypothetical: NO (iv) Antisense : NO (vi) Original source:

(A) Organism: Helicobacter pylori (ix)

(A) Name / Key: misc_character (B) Location: 1 ... 22 (xi) Sequence Description: SEQ ID NO: 183: CTTGAATTAG GGGCAAAGAT CG (2) Information for SEQ ID NO: 184:

(i) Sequence characteristics:

(A) Length: 22 pairs (B) Type: nucleic acid (C) String: double (D) Topology: circular (ii) Molecule type: DNA (genomic) (iii) Hypothetical: NO (iv) Antisense: NO ( (vi) Original source:

(A) Organism: Helicobacter pylori (ix)

(A) Name / Key: misc_charakter (B) Location: 1 ... 22 (xi) Sequence Description: SEQ ID NO: 184:

ATGCGTTTTT ACCCAAAGAA GT

300 2 2 2 2 2 2 2 2 2 (2) Information for SEQ ID NO: 185:

(i) Sequence characteristics: '.

* (A) Length: 22 pairs · · '* (B) Type: nucleic acid. :

(C) String: double (D) Topology: circular (ii) Molecule type: DNA (genomic).

(iii) Hypothetical: NO (iv) Antisense: NO (vi) Original Source:

. (AND). Organism: Helicobacter pylori (ix)

(A) Name / Key: misc_character (B) Location: 1 ... 22 (xi) Sequence Description: SEQ ID NO: 185:

ATAACGCCAC TTCCTTATTG GT '22 (2) Information for SEQ ID NO: 186:

(i) Sequence characteristics:

(A) Length: 19 pairs (B) Type: nucleic acid (C) String: double (D) Topology: circular (ii) Molecule type: DNA (genomic) (iii) Hypothetical: NO (iv) Antisense: NO ( (vi) Original source:

(A) Organism: Helicobacter pylori (ix)

(A) Name / Key: misc_character (B) Location: 1 ... 19 (xi) Sequence Description: SEQ ID NO: 186:

CTTTGGGTAA AAACGCATC.:

(2) Information for SEQ ID NO: 187:

(i) Sequence characteristics:

(A) Length: 20 bp (B) Type: nucleic acid (C) String: double '.

(D) Topology: circular (ii) Molecule type: DNA (genomic) (iii) Hypothetical: NO (iv) Antisense: NO (vi) Original source:

(A) Organism: Helicobacter pylori (ix)

(A) Name / Key: misc_charakter (B) Location: 1 ... 20 (xi) Sequence Description: SEQ ID NO: 187:

CGATCTTTGA TCCTAATTCA 20 (2) Information for SEQ ID NO: 188:

(i) Sequence characteristics:

(A) Length: 19 pairs (B) Type: nucleic acid (C) String: double (D) Topology: circular (ii) Molecule type: DNA (genomic) (iii) Hypothetical: NO (iv) Antisense: NO ( (vi) Original source:

(A) Organism: Helicobacter pylori (ix)

(A) Name / Key: misc_charakter (B) Location: 1 ... 19 (xi) Sequence Description: SEQ ID NO: 188:

ATCAAGTTGC CTATGCTGA

302

(2) Information for SEQ ID NO: 189:

(i) Sequence characteristics:

(A) Length: 22 pairs (B) Type: nucleic acid (C) String: double (D) Topology: circular (ii) Molecule type: DNA (genomic) (iii) Hypothetical: NO (iv) Antisense: NO ( (vi) Original source:

(A) Organism: Helicobacter pylori (ix)

(A) Name / Key: misc_charakter (B) Location: 1 ... 22 (xi) Sequence Description: SEQ ID NO: 189:

TTGAACACTT TTGATTATGC GG (2) Information for SEQ ID NO: 190:

(i) Sequence characteristics:

(A) Length: 23 pairs (B) Type: nucleic acid (C) String: double (D) Topology: circular (ii) Molecule type: DNA (genomic) (iii) Hypothetical: NO (iv) Antisense :. NO (vi) Original source:

(A) Organism: Helicobacter pylori (ix)

(A) Name / Key: misc_charakter (B) Location: 1 ... 23 (xi) Sequence Description: SEQ ID NO: 190:

GGATTATGCG ATTGTTTTAC AAG

303 »9 * ··· (2) Information for SEQ ID NO: .191:

(i) Sequence characteristics:

(A) Length: 21 pairs (b) Type: nucleic acid (C) String: double (D) Topology: circular (ii) Typ. molecules: DNA (genomic) · (iii) Hypothetical: NO (iv) Antisense: NO (vi) Original source:

(A) Organism: Helicobacter pylori (ix)

(A) Name / Key: misc_charakter (B) Location: 1 ... 21 (xi) Sequence Description: SEQ ID NO: 191:

GTCTTTAGCA AAAATGGCGT C (2) Information for SEQ ID NO: 192:

(i) Sequence characteristics:

(A) Length: 21 pairs (B) Type: nucleic acid (C) String: double (D) Topology: circular (ii) Molecule type: DNA (genomic) (iii) Hypothetical: NO (iv) Antisense: NO ( (vi) Original source:

(A) Organism: Helicobacter pylori (ix)

(A) Name / Key: misc_character (B) Location: 1 ... 21 (xi) Sequence Description: SEQ ID NO: 192:

• AATGAGCGTA AGAGAGCCTT C

304

• · * ·· «· · * · * • · · · • • · • · · · · • · • · · · · ··· ··· • · • Λ · • · ·· «· · ·· · • · · ·

(2) Information for SEQ ID NO: 193:

(i) Sequence characteristics:

(A) .Length: 18 pairs (B) Type: nucleic acid (C) String: double (D) Topology: circular (ii) Type, molecules: DNA. (genomic) (iii) Hypothetical: NO (iv) Antisense: NO (vi) Original Source:

(A) Organism: Helicobacter pylori (ix)

(A) Name / Key: misc_character (B) Location: 1 ... 18 (xi) Sequence Description: SEQ ID NO: 193: CTTATGGGGG TATTGTCA (2) Information for SEQ ID NO: 194:

(i) Sequence characteristics:

(A) Length: 18 pairs (B) Type: nucleic acid (C) String: double (D) Topology: circular (ii) Molecule type: DNA (genomic) (iii) Hypothetical: NO (iv) Antisense: NO ( (vi) Original source:

(A) Organism: Helicobacter pylori (ix)

(A) Name / Key: misc_charakter (B) Location: 1 ... 18 (xi) Sequence Description: SEQ ID NO: 194:

AGCATGTGGG TATCCAGC ·· ····

305 (2) Information for SEQ ID NO: 195:

(i) Characteristics, sequence:

(A) Length: 19 pairs (B) Type: nucleic acid (C) String: double (D) Topology: circular (ii) Molecule type: DNA (genomic) (iii) Hypothetical: NO (iv) Antisense: NO ( (vi) Original source:

(A) Organism: Helicobacter pylori (ix)

(A) Name / Key: misc_charakter (B) Location: 1 ... 19 (xi) Sequence Description: SEQ ID NO: 195:

AGGTTGTTGC CTAAAGACT (2) Information for SEQ ID NO: 196:

(i) Sequence characteristics:

(A) Length: 18 pairs (B) Type: nucleic acid (C) String: double (D) Topology: circular (ii) Molecule type: DNA (genomic) (iii) Hypothetical: NO (iv) Antisense: NO ( (vi) Original source:

(A) Organism: Helicobacter pylori (ix)

(A) Name / Key: misc_charakter (B) Location: 1 ... 18 (xi) Description of Sequence: SEQ ID NO: 196:

CTGCCTCCAC CTTTGATC • f

Β

306 V V e e 9 * * * * * * * * * * * * * * 2 * 2 (2) Information for SEQ ID NO: 197:

(i) Sequence characteristics:

(A) Length: 19 pairs of throws (B) Type: nucleic acid 7 (C) String: double ¹ '.

(D) Topology: circular (ii) Molecule type: DNA (genomic) (iii) Hypothetical: NO (iv) Antisense: NO. __________. ..

(vi) Original source:

(A) Organism: Helicobacter pylori (ix)

(A) Name / Key: misc_charakter (B) Location: 1 ... 19 (xi) Sequence Description: SEQ ID NO: .197:

ACCAATATCA ATTGGCACT 19 (2) Information for SEQ ID NO: 198:

(i) Sequence characteristics:

(A) Length: 18 pairs (B) Type: nucleic acid (C) String: double (D) Topology: circular (ii) Molecule type: DNA (genomic) (iii) Hypothetical: NO (iv) Antisense: NO ( (vi) Original source:

(A) Organism: Helicobacter pylori (ix)

(A) Name / Key: misc_charakter (B) Location: 1 ... 18 (xi) Sequence Description: SEQ ID NO: 198:

ACTTGGAAAA GCTCTGCA

307 (2) Information for SEQ ID NO: 199:

(i) Sequence characteristics:

(A) Length: 19 bp (B) Type: nucleic acid (C). String: double '·· (D) Topology:' circular (ii) Molecule type: DNA (genomic) (iii) Hypothetical: NO ( iv) Antisense: NO - ---------- (vi) Original source:

(A) Organism: Helicobacter pylori (ix)

(A) Name / Key: misc_charakter (B) Location: 1 ... 19 (xi) Sequence Description: SEQ ID NO: 199:

CTTGCTTGTC ATATCTAGC (2) Information for SEQ ID NO: 200:

(i) Sequence characteristics:

(A) Length: 18 pairs (B) Type: nucleic acid (C) String: double (D) Topology: circular (ii) Molecule type: DNA (genomic) (iii) Hypothetical: NO (iv) Antisense: NO ( (vi) Original source:

(A) Organism: Helicobacter pylori (ix)

(A) Name / Key: misc_charakter (B) Location: 1 ... 18 (xi) Sequence Description: SEQ ID NO: 200:

GTTGAAGTGT TGGTGCTA i

· · · · ·

308 (2) Information for SEQ ID NO: 201:

. . (i) Sequence characteristics:

(A) Length: 22 pairs of cravings. - ^K (B) Type: nucleic acid (C). String: double '*, (D) Topology: circular'; .

(ii) Type of molecule: DNA (genomic).

(iii) Hypothetical: NO

- (iv) Antisense: NO '(vi) Original source:

(A) Organism: Helicobacter pylori (ix)

(A) Name / Key: misc_charakter (B) Location: 1 ... 22 · (xi) Sequence Description: SEQ ID NO: 201:

CAAGCAAGTG GTTTGGTTTT AG '22 (2) Information for SEQ ID NO: 202: · (i) Sequence characteristics:' (A) Length: 22 pairs (B) Type: nucleic acid (C) String: double (D) Topology: circular (ii) Type of molecule: DNA (genomic) (iii) Hypothetical: NO (iv) Antisense: NO (vi) Original source:

(A) Organism: Helicobacter pylori (ix)

(A) Name / Key: misc_character (B) Location: 1 ... 22 (xi) Sequence Description: SEQ ID NO: 202:

TGGAAAGAGC AAATCATTGA AG

(2) Information for SEQ ID NO: 203:

(i) Sequence characteristics:

(A) Length: 21 pairs (B) Type :, nucleic acid (C) String: double (D) Topology: circular (ii) Molecule type: DNA (genomic) (iii) Hypothetical: NO (iv) Antisense: NO (vi) Original source:

(A) Organism: Helicobacter pylori (ix)

(A) Name / Key: misc_character (B) Location: 1 ... 21 (xi) Sequence Description: SEQ ID NO: 203:

GCCCA.TAATC AAAAAGCCCA T .. 21 »

(2) Information for SEQ ID NO: 204:

(i) Sequence characteristics:

(A) Length: 24 pairs (B) Type: nucleic acid (C) String: double (D) Topology: circular (ii) Molecule type: DNA (genomic) (iii) Hypothetical: NO (iv) Antisense: NO ( (vi) Original source:

(A) Organism: Helicobacter pylori (ix)

(A) Name / Key: misc_charakter (B) Location: 1 ... 24 (xi) Sequence Description: SEQ ID NO: 204:

CTAAAACCAA ACCACTTGCT TGTC

310

(2) Information for SEQ ID NO: 205:

(i) Sequence characteristics:

(A) Length: 16 pairs (B) Type: nucleic acid (C) String: double (D) Topology: circular, (ii) Molecule type: DNA (genomic) (iii) Hypothetical: NO (iv) Antisense: NO - · -; --------------— (vi) Original Source:

(A) Organism: Helicobacter pylori (ix)

(A) Name / Key: misc_charakter (B) Location: 1 ... 16 (xi) Sequence Description: SEQ ID NO: 205:

GTAAAACGAC GGCCAG 16 (2) Information for SEQ ID NO: 206:

(i) Sequence characteristics:

(A) Length: 17 pairs (B) Type: nucleic acid (C) String: double (D) Topology: circular (ii) Molecule type: DNA (genomic) (iii) Hypothetical: NO (iv) Antisense: NO ( (vi) Original source:

(A) Organism: Helicobacter pylori (ix)

(A) Name / Key: misc_charakter (B) Location: 1 ... 17 (xi) Sequence Description: SEQ ID NO: 206:

CAGGAAACAG CTATGAC

311

(2) Information for SEQ ID NO: 207:

(i) Sequence characteristics:

(A) Length: 21 pairs (B) Type: nucleic acid (C) String: double '(D) Topology: circular (ii) Molecule type: DNA (genomic) (iii) Hypothetical: NO .——--- - (iv) Antisense: NO '' · (vi) Original source:

(A) Organism: Helicobacter pylori (ix)

(A) Name / Key: misc_charakter (B) Location: 1 ... 21 te · | (xi) Sequence description: SEQ ID NO: 207:

»ATCTTACCTA TCACCTCAAA T’ /!? (2) Information for SEQ ID NO: 208:

(i) Sequence characteristics:

. (A) Length: 21 pairs of t _t (B) Type: nucleic acid ['(C) String: double | (D) Topology: circular (ii) Molecule type: DNA (genomic)> (iii) Hypothetical: NO (iv) Antisense: NO (vi) Original source:

(A) Organism: Helicobacter pylori (ix)

(A) Name / Key: misc_charakter ⁷ (B) Location: 1 ... 21 (xi) Sequence Description: SEQ ID NO: 208:

AGACAGCAAC ATCTTTGTGA A ·· ····

0 0

000 000

312

The claims

Claims (65)

An isolated nucleic acid comprising a nucleotide sequence encoding an H. pylori polypeptide having at least 60% homology to an amino acid sequence selected from the group consisting of SEQ ID NO: 74 to SEQ ID NO: 146. An isolated nucleic acid comprising a nucleotide sequence encoding a H. pylori polypeptide selected from the group consisting of SEQ ID NO: 74 to SEQ ID NO: 146. An isolated nucleic acid encoding an H. pylori polypeptide comprising a nucleotide sequence having at least 60% homology to a nucleotide sequence selected from the group consisting of SEQ ID NO: 1 to SEQ ID NO: 73, or complementary sequences thereof. The isolated nucleic acid of claim 1 comprising a nucleotide sequence selected from the group consisting of SEQ ID NO: 1 to SEQ ID NO: 73, or complementary sequences thereof. An isolated nucleic acid encoding an H. pylori polypeptide comprising a nucleotide sequence that hybridizes under stringent hybridization conditions to a nucleic acid molecule comprising a nucleotide sequence selected from the group consisting of SEQ ID NO: 1 to SEQ ID NO: 73, or complementary sequences thereof. An isolated nucleic acid comprising a nucleotide sequence of at least 8 nucleotides in length that hybridizes under stringent hybridization conditions to a nucleic acid molecule comprising a nucleotide sequence selected from the group consisting of SEQ ID NO: 1 to SEQ ID NO: 73, or complementary sequences thereof. • «9 · · - 313 · 313 β 313 313 313 313 313 313 313 313 313 313 313 313 313 313 313 313 313 313 313 313 313 1 · 1. 1 ·· · · · An isolated nucleic acid comprising a sequence of nucleotides encoding a H. pylori cell envelope polypeptide or fragment thereof, wherein said nucleic acid is selected from the group consisting of SEQ ID NO: 3, SEQ ID NO: 25, SEQ ID NO: 48 SEQ ID NO: 16, SEQ ID NO: 10, SEQ ID NO: 45, SEQ ID NO: 35, SEQ ID NO: 37, SEQ ID NO. NO: 7, SEQ ID NO: 39, SEQ ID NO: 55, SEQ ID NO NO: 18, SEQ ID NO. 19, SEQ ID NO: 28, SEQ ID NO: 30, SEQ ID NO. 52 SEQ ID NO: 54 SEQ ID NO: 56, SEQ ID NO: 58, SEQ ID NO: 1 SEQ SEQ ID NO: 42; NO: 14, SEQ ID NO: 43, SEQ ID NO NO: 11, SEQ i NO SEQ ID NO: 71 17, SEQ ID NO: 57, SEQ ID NO: 5, SEQ ID NO. 6, SEQ ID NO: 8 and SEQ ID NO: 21, or complementary sequences thereof. The isolated nucleic acid of claim 7, wherein said H. pylori cell envelope polypeptide or fragment thereof is an H. pylori inner membrane polypeptide or fragment thereof encoded by a nucleic acid selected from the group consisting of SEQ ID NO: 3, SEQ ID NO: 25 and SEQ ID NO: 48, or complementary sequences thereof. The isolated nucleic acid of claim 7, wherein said H. pylori cell envelope polypeptide or fragment thereof is an outer membrane polypeptide of H. pylori or a fragment thereof encoded by a nucleic acid selected from the group consisting of SEQ ID NO: 16, SEQ ID NO: 10 SEQ ID NO: 45, SEQ ID NO: 35, SEQ ID NO: 37, SEQ ID NO NO: 7, SEQ ID NO: 39, SEQ ID NO: 55, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 28, SEQ ID NO: 30, SEQ ID NO: 52, SEQ ID NO: 54, SEQ ID NO: 56, SEQ ID NO: 58, SEQ ID NO: 1, SEQ ID NO: 42, SEQ ID NO NO: 14, SEQ ID NO: 43, SEQ ID NO: 11 and SEQ ID NO: 71, or their complementary sequences. The isolated nucleic acid of claim 9, wherein said H. pylori outer membrane polypeptide or fragment thereof is an H. pylori polypeptide having a terminal phenylalanine residue. 9 9 9 9 9,999 • · 9 * ·· And a C-terminal tyrosine moiety or a fragment thereof encoded by a nucleic acid selected from the group consisting of SEQ ID NO: 1 SEQ ID NO: 42, SEQ ID NO: 14, SEQ ID NO: 43,. SEQ ID NO: 11 and SEQ ID NO: 71, or complementary sequences thereof. . The isolated nucleic acid of claim 9, wherein said outer membrane polypeptide of H. pylori 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: 16, SEQ SEQ ID NO: 45, SEQ. SEQ ID NO: 35, SEQ ID NO: 37, SEQ ID NO: 7, SEQ ID NO: 39, SEQ ID NO: 55, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 28, SEQ ID NO. SEQ ID NO: 52, SEQ ID NO: 54, SEQ ID NO: 56 and SEQ ID NO: 58, or their complementary sequences. An isolated nucleic acid comprising a sequence of nucleotides encoding a H. pylori cell envelope polypeptide or fragment thereof selected from the group consisting of SEQ ID NO: 76, SEQ ID NO: 98, SEQ ID NO: 121, SEQ ID NO: 89, SEQ ID NO: 83, SEQ ID NO: 118, SEQ SEQ ID NO: 108, SEQ ID NO: 110, SEQ ID NO: 80, SEQ ID NO: 112, SEQ ID NO NO: 128, SEQ ID NO: 91, SEQ ID NO: 92, SEQ ID NO: 101, SEQ ID NO: 103, SEQ ID NO: 125, SEQ ID NO: 127, SEQ ID NO: 129, SEQ ID NO: &lt; tb &gt; 131, SEQ ID NO: 74, SEQ ID NO: 115, SEQ ID NO: 87, SEQ ID NO: 116, SEQ ID NO: 84, SEQ ID NO: 144, SEQ ID NO: 90, SEQ ID NO: 130, SEQ ID NO: 78, SEQ ID NO: 79, SEQ ID NO: 81, and SEQ ID NO: 94. The isolated nucleic acid of claim 12, wherein said H. pylori cell envelope polypeptide or fragment thereof is an H. pylori inner membrane polypeptide or fragment thereof selected from the group consisting of SEQ ID NO: 76, SEQ ID NO: 98 and SEQ ID NO. NO: 121. 14. The isolated nucleic acid of claim 12, wherein said. The H. pylori cell envelope polypeptide or fragment thereof is an H. pylori outer membrane polypeptide or fragment thereof selected from the group consisting of SEQ ID 118, SEQ ID NO: 108, SEQ ID NO. NO: 89, SEQ ID NO: 83, SEQ ID NO: 112, SEQ ID NO: 101, SEQ ID NO. 128, SEQ ID NO. 103, SEQ ID NO 129, SEQ ID NO: 131, SEQ ID NO 87, SEQ ID NO: 116, SEQ ID NO: and SEQ ID NO: 130. 110, SEQ ID NO 91, SEQ ID NO: 125, SEQ ID NO 74, SEQ ID NO: 84, SEQ ID NO: 80, SEQ ID NO: 92, SEQ ID NO: No. 127, SEQ ID NO: 115, SEQ ID NO: 144, SEQ ID NO: 90 The isolated nucleic acid of claim 14, wherein said H. pylori outer membrane polypeptide or fragment thereof is H. pylori polypeptide having a terminal phenylalanine residue and a C-terminal tyrosine moiety or fragment thereof selected from the group consisting of SEQ ID NO: 74, SEQ ID NO: 115, SEQ ID NO: 87, SEQ ID NO: 116, SEQ ID NO: 84, and SEQ ID NO: 144., The isolated nucleic acid of claim 14, wherein said H. pylori outer membrane polypeptide or fragment thereof is H. pylori polypeptide having a terminal phenylalanine residue or fragment thereof selected from the group consisting of SEQ ID NO: 89, SEQ ID NO: 118, SEQ ID NO: 108, SEQ ID NO: 110, SEQ ID NO: 80, SEQ ID NO: 112, SEQ ID NO: 128, SEQ ID NO: 91, SEQ ID NO: 92, SEQ ID NO: 101 SEQ ID NO: 103 SEQ ID NO: 125 SEQ ID NO: 127 SEQ SEQ ID NO: 129 and SEQ ID NO: 131. An isolated nucleic acid comprising a nucleotide sequence encoding a secreted H. pylori polypeptide or fragment thereof, wherein said nucleic acid is selected from the group consisting of SEQ ID NO: 72, SEQ ID NO: 32, SEQ ID NO: 51, SEQ ID NO. NO: 2, SEQ ID NO: 4, SEQ ID NO: 9, SEQ ID NO: 13, SEQ ID NO: 22, SEQ ID NO: 29, SEQ ID NO: 31, SEQ ID NO: 33, SEQ ID NO: 34, SEQ ID NO: 36, SEQ ID NO: 38, SEQ ID NO: 40, SEQ ID NO: 41, SEQ. - 316 SEQ ID NO: 53 SEQ ID NO: 63 68, or theirs SEQ ID NO: 44, SEQ ID NO: 46, SEQ ID NO: 49, SEQ ID NO: 59, SEQ ID NO: 61, SEQ ID NO: 62, SEQ ID 65, SEQ ID NO: 66, SEQ ID NO: 67 and SEQ ID NO. complementary sequences. An isolated nucleic acid comprising a nucleotide sequence encoding a secreted H. pylori polypeptide or fragment thereof selected from the group consisting of SEQ ID NO: 145, SEQ ID NO: 105, SEQ ID NO: 124, SEQ ID NO: 75, SEQ ID NO. NO: 77, SEQ ID NO NO: 82! SEQ ID 104, SEQ ID NO 111, SEQ ID NO 119, SEQ ID NO 134, SEQ ID NO 139, SEQ ID NO NO: 86, SEQ ID NO 106, SEQ ID NO: 113, SEQ ID NO: 122, SEQ ID NO: 135, SEQ ID NO: 140 and SEQ ID NO: 95, SEQ ID NO 107, SEQ ID NO: 114, SEQ ID NO: 126, SEQ ID NO: 136, SEQ ID NO: 141 102, SEQ ID NO. 109, SEQ ID NO 117, SEQ ID NO 13 2, SEQ. ID NO 138, 'SEQ; ID NO An isolated nucleic acid comprising a nucleotide sequence encoding a H. pylori cell polypeptide or fragment thereof, wherein said nucleic acid is selected from the group consisting of SEQ ID NO: 12, SEQ ID NO: 15, SEQ ID NO: 20, SEQ ID NO. NO: 23, SEQ ID NO: 24, SEQ ID NO: 26, SEQ ID NO: 27, SEQ ID NO: 47, SEQ ID NO: 50, SEQ ID NO: 60, SEQ ID NO: 64, SEQ ID NO: 69, SEQ ID NO. 70 and SEQ ID NO: 73, or complementary sequences thereof. An isolated nucleic acid comprising a nucleotide sequence encoding a H. pylori cell polypeptide or a fragment thereof selected from the group consisting of SEQ ID NO: 85, SEQ ID NO: 88, SEQ ID NO: 93, SEQ ID NO: 96, SEQ ID NO. NO: 97, SEQ ID NO: 99, SEQ ID NO: 100, SEQ ID NO: 120, SEQ ID NO: 123, SEQ ID NO: 133, SEQ ID NO: 137, SEQ ID NO: 142, SEQ ID NO: 143 and SEQ ID NO: 146. 21. A probe comprising a nucleotide sequence consisting of at least 8 nucleotides a nucleotide sequence selected from the group consisting of ···· » 317 from SEQ ID NO: 1 to SEQ ID NO :. 73. or their complementary sequences. ' 22. A recombinant expression vector comprising a nucleic acid according to any one of claims 1, 2, 3, 4, 5, 6, 7, 12, (1, 7, 18, 19 or 20 operably linked to transcriptional). / regulatory. element. A cell comprising the recombinant expression vector of claim 22. 24. A method for producing H. pylori polypeptides comprising culturing the cells of claim 23 under conditions that allow expression of the polypeptides. . and 25. The method of claim 24, further comprising purifying the polypeptides from the cells. A method for detecting the presence of a Helicobacter nucleic acid in a sample comprising (a) contacting the sample with the nucleic acid of any one of claims 6 or 21 in such a way that a hybrid can be formed between the probe and the Helicobacter nucleic acid in the sample; and (b) detecting the hybrid formed in step (a), wherein the detection of the hybrid indicates the presence of Helicobacter nucleic acid in the sample. An isolated H. pylori polypeptide comprising an amino acid sequence having at least 60% homology to an H. pylori polypeptide selected from the group consisting of SEQ ID NO: 74 to SEQ ID NO: 146. - 318 28. An isolated pylori polypeptide encoded by a nucleic acid comprising a nucleotide sequence having at least 60%. homology with a nucleotide sequence selected from the group consisting of. from SEQ ID NO: 1 to SEQ ID NO: 73. The isolated H. pylori polypeptide of claim 28, wherein said polypeptide is encoded by a nucleotide sequence selected from the group consisting of SEQ ID NO: 1 to SEQ ID NO: 73. An isolated H. pylori polypeptide encoded by a nucleic acid that hybridizes under stringent hybridization conditions to a nucleic acid selected from the group consisting of SEQ ID NO: 1 to SEQ ID NO: 73, or complementary sequences thereof. An isolated H. pylori polypeptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 74 to SEQ ID NO: 146. An isolated H. pylori cell envelope polypeptide or fragment thereof, wherein said polypeptide is selected from the group consisting of SEQ ID NO: 76, SEQ ID NO: 98, SEQ ID NO: 121, SEQ ID NO: 89, SEQ ID NO: 83, SEQ ID NO: 118, SEQ ID NO: 108, SEQ ID NO. 110, SEQ ID NO: 80, SEQ ID NO: 112, SEQ ID NO: 128, SEQ ID NO: &lt; tb &gt; 91, SEQ ID NO: 92, SEQ ID NO: 101, SEQ ID NO: 103, SEQ ID NO: &lt; tb &gt; 125, SEQ ID NO: 127, SEQ ID NO: 129, SEQ ID NO: 131, SEQ ID NO: 74, SEQ ID NO: 115, SEQ ID NO: 87, SEQ ID NO: 116, SEQ ID NO: 84, SEQ ID NO: 144, SEQ ID NO: 90, SEQ ID NO: 130, SEQ ID NO: 78, SEQ ID NO: 79, SEQ ID NO: 81, and SEQ ID NO: 94. The isolated polypeptide of claim 32, wherein said H. pylori cell envelope polypeptide or fragment thereof is an H. pylori inner membrane polypeptide or fragment thereof selected from the group consisting of: 319 consisting. from .SEQ ID.NO: 76, .SEQ ID NO: .98, and SEQ ID'NO: 121. The isolated polypeptide of claim 32, wherein said H. pylori cell envelope or fragment thereof is an H. pylori outer membrane polypeptide or fragment thereof selected from the group consisting of SEQ ID NO: 89, SEQ ID NO. No. 83, SEQ ID NO: 118, SEQ ID NO: 108, SEQ ID NO: 110, SEQ ID NO: 80, SEQ ID NO: 112, SEQ ID NO: 128, SEQ ID NO: 91, SEQ ID NO: 92, SEQ ID NO: 101; SEQ ID NO: 103; SEQ ID NO: 125; SEQ ID NO: 127; 129, SEQ ID NO: 131, SEQ ID NO: 74, SEQ ID NO: 115, SEQ ID NO: 87, SEQ ID NO: 116, SEQ ID NO: 84, SEQ ID NO: 144, SEQ ID NO: 90, and SEQ ID NO: 130. The isolated polypeptide of claim 34, wherein said H. pylori outer membrane polypeptide or fragment thereof is an H. pylori polypeptide. having terminal. phenylalanine: residue · and C-terminal tyrosine moiety or. a fragment thereof selected from the group consisting of SEQ ID NO: 74, SEQ ID NO: 115, SEQ ID NO: 87, SEQ ID NO: 116, SEQ ID NO: 84, and SEQ ID NO: 144. The isolated polypeptide of claim 34, wherein said H. pylori outer membrane polypeptide or fragment thereof is H. pylori polypeptide having a terminal phenylalanine residue or fragment thereof selected from the group consisting of SEQ ID NO: 89, SEQ ID NO: 118, SEQ. SEQ ID NO: 108, SEQ ID NO: 110, SEQ ID NO: 80, SEQ ID NO: 112, SEQ ID NO: 128, SEQ ID NO: 91, SEQ ID NO: 92, SEQ SEQ ID NO: 101, SEQ ID NO: 103, SEQ ID NO: 125, SEQ ID NO: 127, SEQ SEQ ID NO: 129 and SEQ ID NO: 131. An isolated H. pylori envelope polypeptide or fragment thereof, wherein said polypeptide is encoded by a nucleic acid selected from the group consisting of SEQ ID NO: 3, SEQ ID NO: 25, SEQ ID NO: 48, SEQ ID NO: 16, SEQ. SEQ ID NO: 10, SEQ ID NO: 45, SEQ ID NO: 35, 320 • ···· SEQ ID NO: 37 SEQ ID -NO: 7, SEQ ID NO: 39, SEQ ID NO: 55, SEQ ID NO NO :, 18, SEQ ID NO NO: 19, SEQ ID NO NO: 28, SEQ ID NO: 30, SEQ ID NO: 52, SEQ ID NO: 54, SEQ ID NO: 56, SEQ ID NO: 58. ‘SEQ ID NO: 1, SEQ ID NO: 42 SEQ ID NO: 14, .SEQ.ID.NO: 43, .SEQ.ID NO: 11, SEQ ID NO. 71, SEQ ID NO: 17, SEQ SEQ ID NO: 57, SEQ ID NO: 5, SEQ ID NO: 6 z SEQ ID NO: 8 a SEQ ID NO: 21. The isolated polypeptide of claim 37, wherein said H. pylori envelope polypeptide or fragment thereof is an H. pylori inner membrane polypeptide or fragment thereof encoded by a nucleic acid selected from the group consisting of SEQ ID NO: 3, SEQ ID NO: 25 and SEQ. ID NO: 48. The isolated polypeptide of claim 37, wherein said H. pylori envelope polypeptide or fragment thereof is a polypeptide. H. pylori outer membrane or a fragment thereof encoded by a nucleic acid selected from the group consisting of SEQ.ID NO: 16, SEQ ID NO: 10, SEQ ID NO: 45, SEQ ID NO: 35, SEQ ID NO: 37, SEQ ID NO: 7, SEQ ID NO: 39, SEQ ID NO: 55, SEQ ID NO: 18, SEQ ID NO: 19, SEQ SEQ ID NO: 28, SEQ ID NO: 30, SEQ ID NO: 52, SEQ ID NO: 54, SEQ ID NO NO: 56, SEQ ID NO: 58, SEQ ID NO: 1, SEQ ID NO: 42, SEQ ID NO: 14, SEQ ID NO: 43, SEQ ID NO: 11, and SEQ ID NO: 71. The isolated polypeptide of claim 39, wherein said H. pylori outer membrane polypeptide or fragment thereof is H. pylori polypeptide having a terminal phenylalanine residue and a C-terminal tyrosine moiety or a fragment thereof encoded by a nucleic acid selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 42, SEQ ID NO: 14, SEQ ID NO: 43, SEQ ID NO: 11, and SEQ ID NO: 71. The isolated polypeptide of claim 39, wherein said H. pylori outer membrane polypeptide or fragment thereof is - 321 H. pylori polypeptide having a terminal phenylalanine residue or fragment thereof encoded by a nucleic acid selected from the group consisting of SEQ ID NO: 16, SEQ ID NO: 45, SEQ ID NO: 35, SEQ ID NO: 37, SEQ : ID NO: 7, SEQ ID SEQ ID NO: 55, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO : 28, SEQ ID NO: 30, .SEQ ID NO: 52, SEQ ID NO: 54, SEQ ID NO: 56 and SEQ ID NO: 58. 42. An isolated H. pylori polypeptide polypeptide or fragment thereof, wherein said polypeptide is selected from the group consisting of SEQ ID NO: 85, SEQ ID NO: 88, SEQ ID NO: 93, SEQ ID NO: 96, SEQ ID NO: 97, SEQ ID NO: 99, SEQ ID NO: 97, SEQ ID NO: 99, SEQ ID NO: 100, SEQ ID NO: 120, SEQ ID NO: 123, SEQ ID NO: 133, SEQ ID NO: 137, SEQ ID NO: 142, SEQ ID NO: 143, and SEQ ID NO: 146. An isolated cellular polypeptide of H. pylori or a fragment thereof, wherein said polypeptide is encoded by a nucleic acid selected from the group consisting of SEQ ID NO: 12, SEQ ID NO: 15, SEQ ID NO. NO: 20, SEQ ! ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 26, SEQ ID NO: 27, SEQ ID NO: 47, SEQ ID NO: 50 SEQ ID NO: 60, SEQ ID NO: 64, SEQ ID NO: 69, SEQ ID NO: 70 and SEQ ID NO: 73 • 44. An isolated secreted H. pylori polypeptide or fragment thereof, wherein said polypeptide is selected from the group consisting of: SEQ SEQ ID NO: 145 105, SEQ ID NO: 124, SEQ ID NO: 75, SEQ ID NO SEQ ID NO: 82 SEQ ID NO: 86, SEQ ID NO : 95, SEQ ID NO: 102, SEQ ID NO: 104, SEQ ID NO: 106; 107, SEQ ID NO: 109, SEQ ID NO: 111, SEQ ID NO: 113; 114, SEQ ID NO: 117, SEQ ID NO: 119, SEQ ID NO: 122; 126, SEQ ID NO: 132, SEQ ID NO: 134, SEQ ID NO: 135, SEQ ID NO: 136, SEQ ID NO: 138, SEQ ID NO: 139, SEQ ID NO: 140 and SEQ ID NO : 141. 45. An isolated secreted H. pylori polypeptide or fragment thereof, wherein said polypeptide is encoded by a nucleic acid. 322 selected from the group consisting of 32, SEQ ID NO. , 51, SEQ ID NO: SEQ ID NO: 13, SEQ IĎ NO: 22, SEQ NO: 33, SEQ ID NO NO: 34, SEQ ID NO 40, SEQ ID NO. ⁴¹ SEQ ID NO: SEQ ID NO: 53 SEQ NO NO: 59, SEQ ID NO: 63, SEQ ID NO. 65, SEQ NO: 68. with SEQ. ID. NO: 7.2, SEQ ID NO: 2, SEQ ID NO: 4, SEQ ID NO: 9, SEQ ID NO: 29, SEQ ID NO: 31, SEQ ID NO: 36, SEQ ID NO: 38,. SEQ ID NO: 44, SEQ ID NO; .46, SEQ ID NO: 49, SEQ ID NO: 61, S.EQ ID NO: 62. SEQ ID NO: 66, SEQ ID NO: '67 and SEQ ID NO 46. A fusion protein comprising an H. pylori polypeptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 74 to SEQ ID NO: 146 operably linked to a non-H. pylori polypeptide. 47. A vaccine composition for the prophylaxis or treatment of an H. pylori infection comprising an effective amount of at least one isolated nucleic acid of any one of claims 1, 2, 3, 4, 5, 6, 7, 12, 17. , 18, 19, or 20. 48. A vaccine composition for the prophylaxis or treatment of an H. pylori infection comprising an effective amount of at least one of the H. pylori polypeptides or fragments thereof according to any one of claims 26, 27, 28, 29, 30, 31, 32, 37. 42, 43, 44 or 45. 49. The vaccine composition of claim 47, further comprising a pharmaceutically acceptable carrier. 50. The vaccine composition of claim 48, further comprising a pharmaceutically acceptable carrier. 51. The vaccine composition of claim 49, wherein the pharmaceutically acceptable carrier comprises an adjuvant. • · 4 4 - 323 44 4 · 4 4 4 « 5 · · « 4 * 4 45 « 52. The vaccine composition of claim 50, wherein the pharmaceutically acceptable carrier comprises an adjuvant. 53. The vaccine composition of claim 49, wherein the pharmaceutically acceptable carrier comprises a delivery system for administration. * 54. The vaccine composition of claim 50, wherein the pharmaceutically acceptable carrier comprises a delivery system for administration. 55. The vaccine composition of claim 53, wherein the delivery system for administration comprises a live vector. 56. The vaccine composition of claim 54, wherein the delivery system comprises a live vector. 57. The vaccine composition of claim 55, wherein the living vector is a bacterium or a virus. 58. The vaccine composition of claim 56, wherein the living vector is a bacterium or a virus. 59. The vaccine composition of claim 53, wherein the pharmaceutically acceptable carrier further comprises an adjuvant. 60. The vaccine composition of claim 54, wherein the pharmaceutically acceptable carrier further comprises an adjuvant. 61. A method for treating or reducing the risk of H. pylori infection 324 In a subject comprising administering to the subject a vaccine composition according to claim 47 such that the treatment or reduction of the risk of H. pylori infection is accomplished. 62. A method for treating or reducing the risk of H. pylori infection in a subject comprising administering to the subject a vaccine composition according to claim 48 such that the risk or infection of H. pylori infection is treated or reduced. . 63. A method for producing a vaccine composition comprising combining at least one of the isolated H. pylori polypeptides or fragments thereof selected from the group consisting of SEQ ID NO: 74 to SEQ ID NO: 146 with a pharmaceutically acceptable carrier to form a vaccine. means. 64. A method for making a vaccine composition comprising (a) providing at least one isolated H. pylori polypeptide or fragment thereof selected from the group consisting of SEQ ID NO: 74 to SEQ ID NO: 146; and (b) combining at least one of said isolated H. pylori polypeptides or fragment thereof with a pharmaceutically acceptable carrier to form a vaccine composition. 65. A method for making a vaccine composition comprising (a) culturing the cells under conditions allowing expression of H. pylori polypeptides or a fragment thereof selected from the group consisting of SEQ ID NO: 74 to SEQ ID NO: 146; (b) isolating said H. pylori polypeptides from the cells; and (c) combining at least one of said isolated H. pylori polypeptides or fragment thereof with a pharmaceutically acceptable carrier to form a vaccine composition.