Method of immunizing humans against Salmonella typhi using a Vi-rEPA conjugate vaccine

Abstract

This invention relates to conjugates of the Vi polysaccharide of S. typhi with the carrier Pseudomonas aeruginosa recombinant exoprotein A (rEPA), and compositions thereof, and to methods of using of these conjugates and/or compositions thereof for eliciting an immunogenic response in humans, including responses which provide protection against, or reduce the severity of, S. typhi bacterial infections. The conjugates, and compositions thereof, are useful as vaccines to induce serum antibodies againt S. typhi and are useful to prevent and/or treat illnesses caused by S. typhi.

1 - 10 . (canceled).  
     
     
         11 . A method of passively immunizing a mammal against  S. typhi,  comprising administering to said mammal an immunologically sufficient amount of a first composition, the first composition comprising antibodies which are immunoreactive with  S. typhi  Vi polysaccharide, said antibodies being obtained from a human after administration to said human of a second composition comprising a conjugate molecule comprising the  S. typhi  Vi polysaccharide covalently bound through a carboxylic acid dihydrazide linker to  Pseudomonas aeruginosa  recombinant exoprotein A.  
     
     
         12 - 15 . (canceled).  
     
     
         16 . The method of  claim 11 , wherein the  S. typhi  Vi polysaccharide comprises an N-acetyl group.  
     
     
         17 . The method of  claim 11 , wherein the  S. typhi  Vi polysaccharide is covalently bound to the  Pseudomonas aeruginosa  recombinant exoprotein A by means of an adipic acid dihydrazide linker.  
     
     
         18 . The method of  claim 11 , wherein the first composition is administered to the mammal at a dosage of about 1 mg/kg to about 10 mg/kg body weight of the mammal.  
     
     
         19 . The method of  claim 11 , wherein the mammal is a human.  
     
     
         20 . The method of  claim 19 , wherein the human is a 2 to 4 year old.  
     
     
         21 . The method of  claim 19 , wherein the human is a 5 to 14 year old.  
     
     
         22 . A composition comprising antibodies which are immunoreactive with  S. typhi  Vi polysaccharide, said antibodies being obtained from a human after administration to said human of a composition comprising a conjugate molecule comprising the  S. typhi  Vi polysaccharide covalently bound through a carboxylic acid dihydrazide linker to  Pseudomonas aeruginosa  recombinant exoprotein A.  
     
     
         23 . The composition of  claim 22 , further comprising antibodies which are immunoreactive with ETA.  
     
     
         24 . The composition of  claim 22 , wherein the composition is chosen from the group consisting of plasma, serum, and gamma globulin fraction.  
     
     
         25 . The composition of  claim 23 , wherein the composition is chosen from the group consisting of plasma, serum, and gamma globulin fraction.  
     
     
         26 . An antibody which is immunoreactive with  S. typhi  Vi polysaccharide which is obtained from a human, after administration to said human of a composition comprising a conjugate molecule comprising the  S. typhi  Vi polysaccharide covalently bound through a carboxylic acid dihydrazide linker to  Pseudomonas aeruginosa  recombinant exoprotein A.