Helicobacter pylori proteins useful for vaccines and diagnostics

Abstract

This invention provides polypeptides of Helicobacter pylori cytotoxin protein. The invention also provides prophylactic and therapeutic vaccines comprising the polypeptides of Helicobacter pylori cytotoxin protein, and methods for their preparation.

What is claimed is:  
     
         1 . A recombinant  Helicobacter pylori  protein, or a derivative or fragment thereof.  
     
     
         2 . The recombinant protein according to  claim 1  wherein the protein is a  Helicobacter pylori  cytotoxin or a precursor, derivative or fragment thereof.  
     
     
         3 . The recombinant protein according to  claim 2  wherein the cytotoxin, precursor, derivative or fragment thereof has the amino acid sequence of FIG. 2, or a portion thereof.  
     
     
         4 . The recombinant protein according to  claim 1  wherein the protein is a  Helicobacter pylori  cytotoxin associated immunodominant antigen, or a derivative or fragment thereof.  
     
     
         5 . The recombinant protein according to  claim 4  wherein the cytotoxin associated immunodominant antigen, derivative or fragment has the amino acid sequence of FIG. 4, or a portion thereof.  
     
     
         6 . The recombinant protein according to  claim 1  wherein the protein is a  Helicobacter pylori  heat shock protein, or a derivative or fragment thereof.  
     
     
         7 . The recombinant protein according to  claim 6 , wherein the heat shock protein, derivative or fragment has the amino acid sequence of FIG. 5 or a portion thereof.  
     
     
         8 . The recombinant protein according to  claim 2  or  3  wherein the recombinant protein exhibits substantially no toxicity, or substantially reduced toxicity.  
     
     
         9 . The recombinant protein according to any one of  claims 4  to  7  wherein the recombinant protein is immunogen and exhibits no functional contribution to toxicity, or a substantially reduced functional contribution to toxicity.  
     
     
         10 . The recombinant protein according to  claim 8  or  9  wherein the recombinant protein is chemically modified to reduce or abolish toxicity or functional contribution to toxicity.  
     
     
         11 . The recombinant protein according to  claim 8  or  9  wherein the recombinant protein contains one or more amino acid substitutions or deletions.  
     
     
         12 . The recombinant protein according to any one of the preceding claims which is labelled or coupled to a solid support.  
     
     
         13 . The recombinant protein according to any one of  claims 1  to  11  for use in the treatment of  Helicobacter pylori  infection.  
     
     
         14 . The recombinant protein according to any one of  claims 1  to  11  for use as a vaccine.  
     
     
         15 . A vaccine or therapeutic composition comprising a recombinant protein according to any one of  claims 1  to  11  and a pharmaceutically acceptable carrier.  
     
     
         16 . The vaccine or therapeutic composition according to  claim 15  comprising two or more recombinant proteins according to any one  claims 1  to  11 .  
     
     
         17 . The vaccine or therapeutic composition according to  claim 16  comprising, in combination, two or more of 
 i) a recombinant  Helicobacter pylori  cytotoxic protein precursor, derivative or fragment thereof,  
 ii) a  Helicobacter pylori  recombinant cytotoxin associated immunodominant antigen, or a derivative or fragment thereof,  
 iii)  Helicobacter pylori  recombinant heat shock protein or a derivative or fragment thereof and/or  
 iv) a  Helicobacter pylori  urease.  
 
     
     
         18 . The vaccine or therapeutic composition according to any one of  claims 15  to  17  comprising an adjuvant.  
     
     
         19 . A method for the preparation of a vaccine or therapeutic composition according to any one of claims  15  or  18  comprising bringing one or more recombinant proteins according to any one of  claims 1  to  11  into association with a pharmaceutically acceptable carrier and optionally an adjuvant.  
     
     
         20 . An immunodiagnostic assay comprising at least one step involving as at least one binding partner, a recombinant protein according to any one of  claims 1  to  12 , optionally labelled or coupled to a solid support.  
     
     
         21 . An immunodiagnosis kit for performing an assay according to  claim 20 , comprising at least one recombinant protein according to any one of  claims 1  to  20 .  
     
     
         22 . Use of one or more recombinant proteins according to any one of  claims 1  to  11  for the manufacture of a medicament for the treatment of  Helicobacter pylori  infection.  
     
     
         23 . A method of treatment of an individual infected with  Helicobacter pylori  comprising administering an effective amount of a recombinant protein according to  1  to  11 .  
     
     
         24 . The method of treatment according to  claim 23  comprising administering an effective amount of, in combination, two or more of 
 i) a recombinant  Helicobacter pylori  cytotoxic protein precursor, derivative or fragment thereof,  
 ii) a  Helicobacter pylori  recombinant cytotoxin associated immunodominant antigen, or a derivative or fragment thereof,  
 iii) a  Helicobacter pylori  recombinant heat shock protein or a derivative or fragment thereof and/or  
 iv) a  Helicobacter pylori  urease.  
 
     
     
         25 . A method of vaccination comprising administering an immunologically effective amount of, in combination, two or more of 
 i) a recombinant  Helicobacter pylori  cytotoxic protein precursor, derivative or fragment thereof,    ii) a  Helicobacter pylori  recombinant cytotoxin associated immunodominant antigen, or a derivative or fragment thereof,    iii) a  Helicobacter pylori  recombinant heat shock protein or a derivative or fragment thereof and/or    iv) a  Helicobacter pylori  urease.    
     
     
         26 . A recombinant polynucleotide encoding a recombinant protein according to any one of  claims 1  to  11 .  
     
     
         27 . A recombinant polynucleotide encoding a  Helicobacter pylori  cytotoxic protein or a derivative or fragment thereof comprising all or part of the nucleotide sequence of FIG. 1.  
     
     
         28 . A recombinant polynucleotide encoding a  Helicobacter pylori  recombinant cytotoxin associated immunodominant antigen or a derivative or fragment thereof comprising all or a part of the nucleotide sequence of FIG. 4.  
     
     
         29 . A recombinant polynucleotide encoding a  Helicobacter pylori  recombinant heat shock protein or a derivative or fragment thereof comprising all or a part of the nucleotide sequence of FIG. 5.  
     
     
         30 . A polynucleotide probe comprising all or part of the recombinant polynucleotide according to any one of  claims 26  to  29 .  
     
     
         31 . A nucleic acid assay wherein in at least one step involves a polynucleotide probe according to  claim 30 .  
     
     
         32 . A kit for performing a nucleic acid assay comprising at least one polynucleotide probe according to  claim 30 .  
     
     
         33 . A polynucleotide amplification process employing a polynucleotide primer wherein in at least one primer is a recombinant polynucleotide comprising all or part of the recombinant polynucleotide according to any one of  claims 26  to  29 .  
     
     
         34 . A kit for performing a polynucleotide amplification process employing a polynucleotide primer wherein in at least one primer is a recombinant polynucleotide comprising all or part of the recombinant polynucleotide according to any one of  claims 26  to  29 .  
     
     
         35 . A vector comprising a recombinant polynucleotide according to any one of  claims 26  to  29 .  
     
     
         36 . A host cell transformed with a vector according to  claim 35 .  
     
     
         37 . A method for the production of a recombinant polypeptide according to any one of  claims 1  to  11 , comprising culturing a host cell according to  claim 36  and isolating the recombinant polypeptide.