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WO1997003360A1 - VACCIN D'HELICOBACTER CONTENANT UN ANTIGENE RECONNU PAR UN ANTICORPS PROTECTEUR MONOCLONAL (IgG 50) - Google Patents

VACCIN D'HELICOBACTER CONTENANT UN ANTIGENE RECONNU PAR UN ANTICORPS PROTECTEUR MONOCLONAL (IgG 50) Download PDF

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Publication number
WO1997003360A1
WO1997003360A1 PCT/US1996/011245 US9611245W WO9703360A1 WO 1997003360 A1 WO1997003360 A1 WO 1997003360A1 US 9611245 W US9611245 W US 9611245W WO 9703360 A1 WO9703360 A1 WO 9703360A1
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WO
WIPO (PCT)
Prior art keywords
igg
monoclonal antibody
helicobacter
ligand
vaccine
Prior art date
Application number
PCT/US1996/011245
Other languages
English (en)
Inventor
John G. Nedrud
Steven J. Czinn
Original Assignee
Oravax, Inc.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Oravax, Inc. filed Critical Oravax, Inc.
Priority to AU63453/96A priority Critical patent/AU6345396A/en
Publication of WO1997003360A1 publication Critical patent/WO1997003360A1/fr

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/12—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from bacteria
    • C07K16/1203—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from bacteria from Gram-negative bacteria
    • C07K16/121—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from bacteria from Gram-negative bacteria from Helicobacter (Campylobacter) (G)
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/195—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria
    • C07K14/205—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria from Campylobacter (G)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies

Definitions

  • This invention relates to methods and compositions for preventing and/or treating Helicobacter infection.
  • Helicobacter is a genus of spiral, gram-negative bacteria which colonize the gastrointestinal tracts of mammals. Several species colonize the stomach, most notably, H. pylori , H. heilmanii , H. felis, and H.
  • H. pylori is the species most of the species most of the species most of the species most of the species most of the species most of the species most of the species most of the species most of the species most of the species most of the species most of the species most of the species most of the species most of the species most of the species most of the species most of the species most of the species most of the species most of the species most of the species most of the species most of the species most of the species most of the species.
  • H. heilmanii and H. felis have also been found to infect humans, but at lower frequencies than H. pylori .
  • Helicobacter infects over 50% of adult populations in developed countries, and nearly 100% in developing countries and some Pacific rim countries, making it one of the most prevalent infections of humans worldwide.
  • H. pylori is the causative agent of most peptic ulcers and chronic superficial (type B) gastritis in humans. H. pylori infection is also associated with atrophy of the gastric mucosa, gastric adenocarcinoma, and non-Hodgkin's
  • lymphoma of the stomach see, e.g., Blaser, J. Infect. Dis. 161:626-633, 1990; Scolnick et al . , Infect. Agents Dis. 1:294-309, 1993; Goodwin et al . ,
  • Helicobacter pylori " Biology and Clinical Practice, CRC Press, Boca Raton, FL, 465 pp, 1993; Northfield et al . , "Helicobacter pylori , “ Infection , Kluwer Acad. Pub., Dordrecht, 178 pp, 1994). If untreated, H. pylori infection and the
  • IgG 50 ligand a Helicobacter polypeptide (hereinafter designated "IgG 50 ligand"), which is recognized by monoclonal antibody IgG 50, and may be used, e .g. , in methods and compositions for preventing and/or treating Helicobacter infection.
  • monoclonal antibody IgG 50 is effective in imparting passive immunity against Helicobacter infection. Accordingly, the invention features a method of preventing or treating Helicobacter (e .g. , H. pylori , H. felis, or H. Heilmanii) infection in a mammal
  • a Helicobacter e.g., H. pylori or H. felis
  • IgG 50 monoclonal antibody
  • Mammals that may be treated using the methods of the invention include, but are not limited to, mammals such as humans, cows, horses, pigs, dogs, cats, sheep, and goats.
  • the invention also features a substantially pure Helicobacter (e .g. , H. pylori or H. felis) polypeptide which is recognized by monoclonal antibody IgG 50, e . g. , a Helicobacter polypeptide having a molecular weight of 16-19 kD, as measured by SDS-PAGE, e .g. , IgG 50 ligand, or a fragment or derivative thereof.
  • compositions containing a polypeptide recognized by IgG 50 (or immunogenic fragments or derivatives thereof), as is described above, in a pharmaceutically acceptable carrier or diluent are also included in the invention.
  • the vaccine composition may also include an adjuvant (e .g. , a cholera toxin, the heat-labile enterotoxin of Escherichia coli , or a fragment or derivative thereof having adjuvant activity).
  • the invention also features a monoclonal antibody (e.g., IgG 50) that recognizes a Helicobacter antigen (e .g. , a Helicobacter antigen which has a molecular weight of approximately 16-19 kD, as measured by SDS-PAGE, e.g., IgG 50 ligand) which is recognized by a monoclonal antibody (e.g., IgG 50) that recognizes a Helicobacter antigen (e .g. , a Helicobacter antigen which has a molecular weight of approximately 16-19 kD, as measured by SDS-PAGE, e.g., IgG 50 ligand) which is recognized by a monoclonal antibody (e.g., IgG 50) that recognizes a Helicobacter antigen (e .g. , a Helicobacter antigen which has a molecular weight of approximately 16-19 kD, as measured by SDS-PAGE, e.g., IgG 50
  • monoclonal antibody IgG 50 Such a monoclonal antibody may be used in a method for preventing or treating
  • Helicobacter infection in a mammal involving administering (e.g., to a mucosal surface, e .g. , orally) the monoclonal antibody to the mammal.
  • an antibody may also be used in a method of detecting a Helicobacter antigen in a sample.
  • the sample is contacted with the monoclonal antibody and detection of the antibody bound to the sample is used as an indication of the presence of the antigen in the sample.
  • This method may employ standard immunological assays, e.g., Western blot analysis or ELISA.
  • the invention also features a substantially pure nucleic acid (DNA or RNA) comprising a nucleotide sequence encoding a Helicobacter antigen recognized by monoclonal antibody IgG 50 (e.g., a Helicobacter antigen which has a molecular weight of approximately 16-19 kD, as measured by SDS-PAGE, e .g. , IgG 50 ligand).
  • a Helicobacter antigen recognized by monoclonal antibody IgG 50 (e.g., a Helicobacter antigen which has a molecular weight of approximately 16-19 kD, as measured by SDS-PAGE, e .g. , IgG 50 ligand).
  • protein or “polypeptide” is meant any chain of amino acids, regardless of length or post-translational modification (e.g., glycosylation or phosphorylation).
  • substantially pure is meant a preparation which is at least 60% by weight (dry weight) the compound of interest, e.g., a IgG 50 ligand polypeptide or IgG 50 ligand-specific antibody.
  • the preparation is at least 75%, more preferably at least 90%, and most preferably at least 99%, by weight the compound of interest. Purity can be measured by any appropriate method, e.g., column chromatography, polyacrylamide gel electrophoresis, or HPLC analysis.
  • purified DNA is meant DNA that is not immediately contiguous with both of the sequences (e . g. , coding sequences) with which it is immediately contiguous (one on the 5' end and one on the 3' end) in the
  • the term therefore includes, for example, a recombinant DNA which is incorporated into a vector; into an autonomously replicating plasmid or virus; or into the genomic DNA of a prokaryote or eukaryote, or which exists as a separate molecule (e.g., a cDNA or a genomic DNA fragment produced by PCR or restriction endonuclease treatment) independent of other sequences. It also includes a recombinant DNA which is part of a hybrid gene encoding additional polypeptide sequence.
  • Pig. 1 is a graph showing the percentages of mice protected against H. felis challenge by passive oral immunization with the indicated monoclonal antibodies, including IgG 50 (50), which were raised against H. felis lysates. Protection was measured by urease broth assays carried out on gastric biopsies obtained one week after inoculation.
  • the Helicobacter antigen recognized by monoclonal antibody IgG 50 can be used in
  • H. pylori a compound that has a high degree of activity in the central nervous system.
  • H. felis a compound that has a high degree of activity in the central nervous system.
  • H. heilmanii a compound that has a high degree of activity in the central nervous system.
  • IgG 50 ligand or an immunogenic fragment or derivative thereof, is
  • a mucosal e.g., intranasal, oral, ocular, gastric, rectal, vaginal, intestinal, or urinary tract
  • a mucosal e.g., intranasal, oral, ocular, gastric, rectal, vaginal, intestinal, or urinary tract
  • a cholera toxin CT
  • LT heat- labile enterotoxin of Escherichia coli
  • a cholera toxin CT
  • LT heat- labile enterotoxin of Escherichia coli
  • RIBI immunoChem, Hamilton, MT
  • aluminum hydroxide may be used in parenteral administration.
  • Recombinant attenuated vectors derived from microorganisms, e.g., bacteria or viruses, such as Salmonella, Shigella, vaccinia virus, rotavirus, adenovirus, BCG virus, and poliovirus may also be used for administration of the vaccines of the invention (see, e . g. , Lagranderie et al . , Vaccine 11:1283, 1993; Morris et al .
  • IgG 50 ligand polypeptides which may be used in the vaccination methods of the invention may be prepared using any of several standard methods. For example, standard recombinant DNA methods may be employed (see, e.g., Ausubel et al., Eds., Current Protocols in
  • a suitable host cell is transformed with an appropriate expression vector containing all or part of an IgG 50 ligand-encoding nucleic acid (e.g., DNA or RNA) fragment.
  • Nucleic acids encoding IgG 50 ligand are isolated using standard methods (see, e.g., Ausubel et al . , supra).
  • monoclonal antibody IgG 50 which specifically recognizes IgG 50 ligand, may be used to immunoprecipitate IgG 50 ligand from Helicobacter lysates (see Fig. 2 and below).
  • the immunoprecipitated polypeptide may be further purified by, e.g., sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), after which it is transferred onto a membrane (e.g., a PVDF or nitrocellulose membrane), from which it is eluted for microsequence analysis (see, e.g., Ausubel et al . , supra).
  • degenerate primers may be designed for use in polymerase chain reaction (PCR) methods for generating probes which may be used for screening
  • Helicobacter e .g. , H. pylori or H. felis
  • DNA libraries e.g., cDNA libraries
  • IgG 50 ligand see, e.g., Ausubel et al . , supra.
  • a nucleic acid clone encoding IgG 50 ligand may also be obtained by screening an expression library, e.g., a ⁇ GT11 expression library, prepared from Helicobacter (e .g. , H. pylori or H. felis) nucleic acid (see, e.g., Blanchard et al . , Infection and Immunity 63 (4) :1394-1399, 1995; Ausubel et al . , supra).
  • an expression library e.g., a ⁇ GT11 expression library, prepared from Helicobacter (e .g. , H. pylori or H. felis) nucleic acid (see, e.g., Blanchard et al . , Infection and Immunity 63 (4) :1394-1399, 1995; Ausubel et al . , supra).
  • IgG 50 ligand polypeptides may be produced in a prokaryotic host (e.g., E. coli) or in a eukaryotic host (e.g., yeast cells (e.g., Saccharomyces cerevisiae), mammalian cells (e.g., COS1, NIH3T3, or JEG3 cells), or arthropod cells (e.g., Spodoptera frugiperda (SF9) cells)).
  • yeast cells e.g., Saccharomyces cerevisiae
  • mammalian cells e.g., COS1, NIH3T3, or JEG3 cells
  • arthropod cells e.g., Spodoptera frugiperda (SF9) cells
  • ATCC American Type Culture Collection
  • IgG 50 ligand polypeptides may also be produced by chemical synthesis, e.g., by the method described in Solid Phase Peptide
  • IgG 50 ligand may be purified from Helicobacter cultures, using standard methods.
  • HCV 50 ligand In addition to native, full length, Helicobacter IgG 50 ligand, polypeptide fragments of IgG 50 ligand, or IgG 50 ligand polypeptides (or polypeptide fragments of IgG 50 ligand) containing mutations, may be used in the invention, provided that antigenicity is retained.
  • IgG 50 ligand polypeptides are made by standard methods, including, e.g., recombinant, chemical synthetic, or proteolytic methods (see, e.g., Ausubel et al . , supra).
  • IgG 50 ligand fragments should be at least 10 amino acids in length, for example 50-200 amino acids in length, in order to maintain antigenicity.
  • Genes encoding fragments of IgG 50 ligand, and/or IgG 50 ligand containing mutations are made using standard methods (see, e.g., Ausubel et al . , supra).
  • Fragments and derivatives of IgG 50 ligand which are included in the invention may be screened for antigenicity using standard methods in the art, e.g., by measuring induction of a mucosal immune response or induction of protective and/or therapeutic immunity (see below).
  • Fusion proteins containing IgG 50 ligand (or a fragment or derivative thereof) fused to, e.g., an adjuvant (e.g., CT, LT, or a fragment or derivative thereof having adjuvant activity), are also included in the invention, and can be prepared using standard methods (see, e.g., Ausubel et al . , supra).
  • an adjuvant e.g., CT, LT, or a fragment or derivative thereof having adjuvant activity
  • the vaccines of the invention may be covalently coupled or cross-linked to adjuvants (see, e .g. , Cryz et al . ,
  • the amount of vaccine administered depends on, e.g., the particular vaccine antigen, whether an adjuvant is co-administered with the antigen, the type of adjuvant co-administered, the mode and frequency of
  • ⁇ g and 100 mg are administered in amounts ranging between, e.g., 1 ⁇ g and 100 mg. If adjuvants are administered with the vaccines, amounts ranging between, e.g., 1 ng and 1 mg may be used. Administration is repeated as necessary, as can be determined by one skilled in the art. For example, a priming dose can be followed by 3 booster doses at weekly intervals.
  • Antibodies against IgG 50 ligand e.g., monoclonal antibodies such as IgG 50
  • Monoclonal antibodies against IgG 50 ligand are produced using standard immunological methods (see, e . g. , Coligan et al., Eds., Current Protocols in Immunology, John Wiley & Sons, Inc., New York, New York, 1994). Antigens for use in these methods may be obtained, e.g., by
  • Antibodies of any isotype may be used in the invention.
  • purified polyclonal antibodies single chain antibodies, chimeric antibodies (e.g., human/murine chimeric antibodies), humanized antibodies (e.g.,
  • fragments which recognize IgG 50 ligand may be used in the invention.
  • antibodies e.g., monoclonal antibodies which recognize IgG 50 ligand, e.g., IgG 50, are administered to a mucosal (e.g., oral or intragastric) surface of a mammal.
  • a mucosal e.g., oral or intragastric
  • the amount of antibody used in this method can be determined by one skilled in the art.
  • the IgG 50 ligand polypeptides, nucleic acids, and antibodies of the invention may also be used for
  • the H. felis mouse model is an accepted model for H. pylori infection of humans (see, e .g. , Lee et al . , European Journal of Gastroenterology and Hepatology
  • Monoclonal antibodies (including IgG 50) against sonicated H. felis lysates were produced by a
  • mice obtained from the Jackson Laboratory (Bar Harbor, Maine) were immunized intragastrically four times over a 6-week period. The first three times, the mice were immunized with 2 mg of sonicated H. felis plus 10 ⁇ g cholera toxin (Sigma Chemical Co., St. Louis, MO). For the last immunization, the cholera toxin was omitted, and, in addition to the intragastric immunization, the mice received an intravenous boost of 2 mg of H. felis sonicate.
  • cholera toxin Sigma Chemical Co., St. Louis, MO
  • mice were sacrificed, and their spleen cells were hybridized to SP2/01-Ag myeloma cells (ATCC accession number CRL 8006), using standard methods (see, e.g., Harlow et al ., Antibodies, A Laboratory Manual, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New York; Coligan et al . , supra).
  • Clones obtained by limited dilution were screened for secretion of anti-H. felis monoclonal antibodies by an enzyme-linked immunosorbent assay (ELISA) using an H. felis outer-membrane
  • OMPs as an antigen (Blanchard et al . , supra).
  • IgG 50 monoclonal antibodies which recognize H. felis antigens, including IgG 50, were isolated using this method.
  • CFU colony-forming units
  • PBS phosphate-buffered saline
  • mice Four hundred ⁇ l ( ⁇ 10 6 organisms) of the bacteria/antibody mixture was administered to mice by gastric intubation. The mice received an additional 200 ⁇ l of ascites fluid at 4, 8, and 24 hours. Mice were necropsied on day 9, and their gastric tissues were examined for H. felis colonization by urea broth assays (see, e . g. , Blanchard et al . , supra). Using these methods, monoclonal antibody IgG 50 was found to be effective at passively protecting mice from H. felis challenge (see Fig. 1 and Table 1, below).
  • Monoclonal antibody IgG 50 is produced by:
  • hybridoma cell line #50-G 6 -B 7 which was deposited with the ATCC (Rockville, MD) on June 30, 1995, and assigned ATCC accession number HB-11952.
  • IgG 50 immunoprecipitates two bands (Fig. 2, lane C) from H. felis lysates which are close to each other in molecular weight. Amino acid analysis of the polypeptides in these bands shows that their amino acid contents are very similar (Table 2 (upper band) and Table 3 (lower band)). Other embodiments are in the following claims. What is claimed is:

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Biochemistry (AREA)
  • Biophysics (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Medicinal Chemistry (AREA)
  • Molecular Biology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
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  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)

Abstract

L'invention concerne des polypeptides d'Helicobacter qui sont reconnus par l'anticorps monoclonal IgG 50, des anticorps monoclonaux (par exemple IgG 50) qui reconnaissent ces polypeptides, et des procédés pour prévenir et/ou traiter les infections par Helicobacter faisant appel à ces polypeptides et ces anticorps monoclonaux. La figure montre la protection passive de souris contre Helicobacter felis avec des anticorps monoclonaux.
PCT/US1996/011245 1995-07-07 1996-07-02 VACCIN D'HELICOBACTER CONTENANT UN ANTIGENE RECONNU PAR UN ANTICORPS PROTECTEUR MONOCLONAL (IgG 50) WO1997003360A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU63453/96A AU6345396A (en) 1995-07-07 1996-07-02 Helicobacter vaccine antigen recognized by a protective monoclonal antibody (igg 50)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US49942295A 1995-07-07 1995-07-07
US08/499,422 1995-07-07

Publications (1)

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WO1997003360A1 true WO1997003360A1 (fr) 1997-01-30

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Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1998024885A1 (fr) * 1996-12-06 1998-06-11 Sanitaria Scaligera S.P.A. ANTIGENE D'HELICOBACTER PYLORI POSSEDANT UN POIDS MOLECULAIRE APPARENT DE 16 ± 2 kDa, ANTICORPS SPECIFIQUE, ET SON UTILISATION POUR LA DETECTION DE CET ANTIGENE
WO1999012037A1 (fr) * 1997-09-02 1999-03-11 Massachusetts Institute Of Technology Compositions et procedes pour le traitement de la bursite infectieuse
US6419926B2 (en) * 1997-04-11 2002-07-16 Ghen Corporation Specific antibodies for use in preparation of pharmaceutical compositions useful in the prevention or treatment of gastritis, gastric ulcers and duodenal ulcers
WO2005113603A1 (fr) * 2004-05-18 2005-12-01 Universite De Lausanne Eradication d'une infection a helicobacter par activation de mastocytes dans l'estomac

Citations (1)

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Publication number Priority date Publication date Assignee Title
US5262156A (en) * 1991-08-12 1993-11-16 Hycor Biomedical, Inc. Antigenic compositions and their use for the detection of Helicobacter pylori

Patent Citations (1)

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US5262156A (en) * 1991-08-12 1993-11-16 Hycor Biomedical, Inc. Antigenic compositions and their use for the detection of Helicobacter pylori

Non-Patent Citations (8)

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Title
EUROPEAN JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, 1993, Vol. 5, (Suppl. 2), RAPPUOLI et al., "Development of a Vaccine Against Helicobacter Pylori: a Short Review", pages 576-578. *
INFECTION AND IMMUNITY, February 1989, Vol. 57(2), CLAYTON et al., "Molecular Cloning and Expression of Campylobacter Pylori Species Specific Antigens in Escherichia Coli K-12", pages 623-629. *
INFECTION AND IMMUNITY, July 1991, Vol. 39(7), CZINN et al., "Oral Immunization Against Helicobacter Pylori", pages 2359-2363. *
INTERNATIONAL WORKSHOP ON CAMPYLOBACTER, HELICOBACTER AND RELATED ORGANISMS, 7-10 October, S10, PAVLOVSKIS et al., "Adjuvant Effect of Escherichia Coli Heat-Labile Enterotoxin on Host Immune Response Following Vaccination with Non-Viable Campylobacter Antigens". *
JOURNAL OF CLINICAL MICROBIOLOGY, August 1991, Vol. 29(8), DROUET et al., "Characterization of an Immunoreactive Species-Specific 19-Kilodalton Outer Membrane Protein from Helicobacter Pylori by Using a Monoclonal Antibody", pages 1620-1624. *
VACCINE, 1992, Vol. 10(2), McGHEE et al., "The Mucosal Immune System from Fundamental Concepts to Vaccine Development", pages 75-88. *
VACCINE, April 1993, Vol. 11(6), CZINN et al., "Protection of Germ-Free Mice from Infection by Helicobacter Felis after Active Oral or Passive IgA Immunization", pages 637-642. *
VACCINE, June 1988, Vol. 6, CLEMENTS et al., "Adjuvant Activity of Escherichia Coli Heat-Labile Enterotoxin and Effect on the Induction of Oral Tolerance in Mice to Unrelated Protein Antigens", pages 269-277. *

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1998024885A1 (fr) * 1996-12-06 1998-06-11 Sanitaria Scaligera S.P.A. ANTIGENE D'HELICOBACTER PYLORI POSSEDANT UN POIDS MOLECULAIRE APPARENT DE 16 ± 2 kDa, ANTICORPS SPECIFIQUE, ET SON UTILISATION POUR LA DETECTION DE CET ANTIGENE
US6419926B2 (en) * 1997-04-11 2002-07-16 Ghen Corporation Specific antibodies for use in preparation of pharmaceutical compositions useful in the prevention or treatment of gastritis, gastric ulcers and duodenal ulcers
US6793921B2 (en) 1997-04-11 2004-09-21 Nisshin Pharma Inc. Specific antibodies for use in preparation of pharmaceutical compositions useful in the prevention or treatment of gastritis, gastric ulcers and duodenal ulcers
WO1999012037A1 (fr) * 1997-09-02 1999-03-11 Massachusetts Institute Of Technology Compositions et procedes pour le traitement de la bursite infectieuse
US6599509B2 (en) 1997-09-02 2003-07-29 Massachusetts Institute Of Technology Compositions and methods comprising helicobacter antigens for treatment and prevention of inflammatory bowel disease
WO2005113603A1 (fr) * 2004-05-18 2005-12-01 Universite De Lausanne Eradication d'une infection a helicobacter par activation de mastocytes dans l'estomac

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ZA965734B (en) 1998-01-08

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