Immunogenic detoxified mutant e. coli lt-a toxin

Abstract

An immunogenic detoxified protein is provided which comprises the amino acid sequence of subunit A of an E. coli heat labile toxin (LT-A) or a fragment thereof in which at least amino acid Ala-72 of the A subunit is mutated, preferably by substitution with Arg. The toxoid is useful as vaccine against an enterotoxigenic strain of E. coli and is produced by recombinant DNA means by site-directed mutagenesis. It is also an effective adjuvant.

1 . An immunogenic detoxified protein comprising the amino acid sequence of subunit A of an  E.coli  heat labile toxin (LT-A), or a fragment thereof, for use as a mucosal adjuvant, wherein amino acid Ala-72 in said sequence or fragment is substituted with an arginine residue.  
     
     
         2 . An immunogenic composition comprising (i) a pharmaceutically acceptable carrier and (ii) an immunogenic detoxified protein comprising the amino acid sequence of subunit A of an  E.coli  heat labile toxin (LT-A), or a fragment thereof, for use as a vaccine, wherein amino acid Ala-72 in said sequence or fragment is substituted with an arginine residue.  
     
     
         3 . An immunogenic composition according to  claim 2 , further comprising a second immunogenic antigen.  
     
     
         4 . The use of an immunogenic detoxified protein comprising the amino acid sequence of subunit A of an  E.coli  heat labile toxin (LT-A), or a fragment thereof, in the manufacture of a vaccine, wherein amino acid Ala-72 in said sequence or fragment is substituted with an arginine residue.  
     
     
         5 . The use of claims  4 , wherein said vaccine comprises a second immunogenic antigen.  
     
     
         6 . A method of vaccinating a mammal, comprising administering (i) an effective amount of an immunogenic detoxified protein comprising the amino acid sequence of subunit A of an  E.coli  heat labile toxin (LT-A), or a fragment thereof, wherein amino acid Ala-72 in said sequence or fragment is substituted with an arginine residue, optionally in association with (ii) a second immunogenic antigen.