Bacterial antigens and vaccine compositions

Abstract

The present invention relates to recombinant polypeptides which constitute Helicobacter pylori surface-exposed antigens with an approximate molecular weight of 29 kDa. The invention furthermore provides nucleic acid molecules coding for the said polypeptides, as well as vectors and host cells comprising such nucleic acid molecules. The said recombinant polypeptides are useful for the diagnosis of H. pylori infections and for the manufacture of vaccine compositions which will elicit a protective immune response against such infections, said vaccine compositions being suitable for both therapeutic and prophylactic use.

1 . A recombinant polypeptide which has an amino acid sequence identical with, or substantially similar to, a  Helicobacter pylori  surface-exposed exposed antigen with an approximate molecular weight of 29 kDa.  
     
     
         2 . A polypeptide according to  claim 1  which amino acid sequence is identical with, or substantially similar to, positions 1-260 or 28-260 in SEQ ID NO: 2 or SEQ ID NO: 4 in the Sequence Listing.  
     
     
         3 . A peptide with a length of at least 5 amino acids comprising an immunogenic epitope of a polypeptide according to  claim 1 .  
     
     
         4 . An isolatedi nucleic acid molecule which has a nucleotide sequence coding for a polypeptide according to  claim 1  or  2 .  
     
     
         5 . An isolated nucleic acid molecule selected from: 
 (a) nucleic acid molecules comprising a nucleotide sequence which is identical with, or substantially similar to, positions 796-1572 or 874-1572 in SEQ ID NO: 1 or SEQ ID NO: 3 in the Sequence Listing;    (b) nucleic acid molecules comprising a nucleotide sequence capable of hybridizing to a nucleotide sequence complementary to the polypeptide coding region of a nucleic acid molecule as defined in (a) and which codes for a polypeptide according to  claim 1  or  2 , or a functionally equivalent modified form thereof; and    (c) nucleic acid molecules comprising a nucleic acid sequence which is degenerate as a result of the genetic code to a nucleotide sequence as defined in (a) or (b) and which codes for a polypeptide according to  claim 1  or  2 , or a functionally equivalent modified form thereof.    
     
     
         6 . A vector which comprises the nucleic acid molecule according to  claim 4  or  5 .  
     
     
         7 . A vector according to  claim 6  which is the plasmid vector pAE1 (NCIMB 40732).  
     
     
         8 . A vector according to  claim 6  which is an expression vector capable of mediating the expression of a DNA molecule according to  claim 4  or  5 .  
     
     
         9 . A vector according to  claim 8  which is the plasmid vector pS863.  
     
     
         10 . A host cell harbouring a vector according to any one of  claims 6  to  9 .  
     
     
         11 . A proces for production of a polypeptide which is a  Helicobacter pylori  surface-exposed 29 kDa antigen, which comprises culturing a host cell transformed with an expression vector according to  claim 8  or  9  under conditions whereby said polypeptide is produced, and recovering said polypeptide.  
     
     
         12 . A polypeptide or peptide according to any one of  claims 1  to  3  for use in therapy.  
     
     
         13 . A polypeptide or peptide according to any one of  claims 1  to  3  for use in the diagnosis of  Helicobacter pylori  infection.  
     
     
         14 . A polypeptide or peptide according to any one of  claims 1  to  3  for use as a vaccine.  
     
     
         15 . A vaccine composition for inducing a protective immune response to  Helicobacter pylori  infection, comprising an immunogenically effective amount of a polypeptide according to any one of  claims 1  to  3 , or a modified form of said polypeptide which retains the capability to induce protective immunity against  Helicobacter pylori  infection, optionally together with a pharmaceutically acceptable carrier or diluent.  
     
     
         16 . A vaccine composition according to  claim 15  for use as a therapeutic vaccine in a mammal, including man, which is infected by  Helicobacter pylori.    
     
     
         17 . A vaccine composition according to  claim 15  for use as a prophylactic vaccine to protect a mammal, including man, from infection by  Helicobacter pylori.    
     
     
         18 . Use of a polypeptide according to any one of  claims 1  to  3 , or a modified form of said antigen which retains the capability to induce protective immunity against  Helicobacter pylori  infection, in the manufacture of a composition for the treatment, prophylas or diagnosis of  Helicobacter pylori  infection.  
     
     
         19 . Use of a polypeptide according to any one of  claims 1  to  3 , or a modified form of said antigen which retains the capability to induce protective immunity against  Helicobacter pylori  infection, in the manufacture of a diagnostic kit for diagnosis of  Helicobacter pylori  infection.  
     
     
         20 . Use of a polypeptide according to any one of  claims 1  to  3 , or a modified form of said polyppeptide which retains the capability to induce protective immunity against  Helicobacter pylori  infection, in the manufacture of a vaccine for use in eliciting a protective immune response against  Helicobacter pylori.    
     
     
         21 . A method of eliciting in a mammal a protective immune response against  Helicobacter pylori  infection, said method comprising the step of administering to the said mammal an immunologically effective amount of a vaccine composition according to any one of  claims 15  to  17 .  
     
     
         22 . A method according to  claim 21  wherein the said mammal is a human.  
     
     
         23 . A method of in vitro diagnosis of  Helicobacter pylori  infection comprising at least one step wherein a polypeptide according to any one of  claims 1  to  3 , optionally labelled or coupled to a solid support, is used.  
     
     
         24 . A method according to  claim 23  comprising the steps 
 (a) contacting a said polypeptide, optionally bound to a solid support, with a body fluid taken from a mammal; and  
 (b) detecting antibodies from the said body fluid binding to the said polypeptide.  
 
     
     
         25 . A diagnostic kit for the detection of  Helicobacter pylori  infection in a mammal, including man, comprising components which enable the method according to  claim 23  or  24  to be carried out.