Non-toxic double mutant forms of pertussis toxin as adjuvants

Abstract

The invention relates to the use of an antigen which is a non-toxic double mutant form of pertussis toxin for the manufacture of a vaccine composition for intranasal administration to induce an immune response against B. pertussis infection. The invention also relates to the use of a non-toxic double mutant form of pertussis toxin for the manufacture of an adjuvant composition for stimulating or enhancing a protective immune response of an antigen co-administered therewith. The non-toxic double mutant is preferably one in which the glutamic acid 129 amino acid in the S 1 sub-unit has been substituted by glycine and the arginine 9 amino acid has been substituted by lysine.

1 .- 36 . (canceled) 
     
     
         37 . A method of stimulating or enhancing a protective immune response to an antigen in a mammal, which method comprises administering to said mammal with the antigen an effective adjuvant amount of a non-toxic double mutant form of pertussis toxin, said antigen being one which elicits a protective immune response when administered with said effective adjuvant amount of said non-toxic double mutant form of pertussis toxin, wherein said non-toxic double mutant form of pertussis toxin comprises an S 1  sub-unit containing an amino acid at position 129 which is other than glutamic acid and containing an amino acid at position 9 which is other than arginine. 
     
     
         38 . A method according to  claim 37 , wherein the amino acid at position 129 in the S 1  sub-unit is glycine. 
     
     
         39 . A method according to  claim 37  wherein the amino acid at position 9 in the S 1  sub-unit is lysine. 
     
     
         40 . A method according to  claim 37  wherein the antigen and the non-toxic double mutant form of pertussis toxin are administered simultaneously or sequentially. 
     
     
         41 . A method according to  claim 40  wherein the antigen and the non-toxic double mutant form of pertussis toxin are present in admixture in a composition administered to the mammal. 
     
     
         42 . A method according to  claim 37  wherein the antigen is selected from the group consisting of tetanus toxin C-fragment, and one or more immunogenic fragments thereof. 
     
     
         43 . A method according to  claim 37  wherein the antigen is selected from the group consisting of FHA and P69. 
     
     
         44 . A method according to  claim 43  wherein both FHA and P69 are administered with the non-toxic double mutant form of pertussis toxin. 
     
     
         45 . A vaccine composition comprising an antigen, an adjuvant capable of enhancing the immune response to the antigen in a mammal to which the composition is administered, and a pharmaceutically acceptable carrier, wherein the adjuvant is a non-toxic double mutant form of pertussis toxin comprises an S 1  sub-unit containing an amino acid at position 129 which is other than glutamic acid and containing an amino acid at position 9 which is other than arginine. 
     
     
         46 . A vaccine composition according to  claim 45 , wherein the amino acid at position 129 in the S 1  sub-unit is glycine. 
     
     
         47 . A vaccine composition according to  claim 45 , wherein the amino acid at position 9 in the S 1  sub-unit is lysine. 
     
     
         48 . A vaccine composition according to  claim 45 , wherein the antigen is selected from the group consisting of tetanus toxin C-fragment, and one or more immunogenic fragments thereof. 
     
     
         49 . A vaccine composition according to  claim 45 , wherein the antigen is selected from the group consisting of FHA and P69. 
     
     
         50 . A vaccine composition according to  claim 49 , which comprises both FHA and P69.