Nontoxic mucosal adjuvant

Abstract

The present invention is directed to immunogenic compositions comprising an immunologically effective amount of an antigen against which an immune response is desired and a mucosal adjuvant, wherein the mucosal adjuvant comprises a detoxified mutant A subunit or detoxified mutant holotoxin of pertussis toxin (PT) or Pseudomonas endotoxin A, wherein the antigen is not the detoxified mutant. The present invention is also directed to methods for the manufacture of the same, and to methods of enhancing an immune response to an antigen in a mammal comprising administering to the mammal the immunogenic compositions.

1 . A pharmaceutical composition comprising a non-toxic mucosal adjuvant in admixture with a second antigen.  
     
     
         2 . A composition according to  claim 1  wherein the non-toxic mucosal adjuvant is a detoxified mutant of a bacterial ADP-ribosylating toxin.  
     
     
         3 . A composition according to  claim 2  wherein the non-toxic adjuvant is a detoxified mutant of CT or LT.  
     
     
         4 . A composition according to  claim 2  or  claim 3  wherein the non-toxic mucosal adjuvant comprises one or more amino acid additions, deletions or substitutions in the A subunit of the holotoxin.  
     
     
         5 . A composition according to  claim 4  wherein the non-toxic mucosal adjuvant is LTK7.  
     
     
         6 . Use of a non-toxic mutant as defined in any one of  claims 2  to  5  as a mucosal adjuvant in the preparation of a composition for mucosal administration.  
     
     
         7 . Use according to  claim 6 , wherein the composition is a vaccine.  
     
     
         8 . Use according to  claim 7 , wherein the vaccine is for use in prophylactic or therapeutic applications.  
     
     
         9 . Use according to any on of  claims 6  to  8 , wherein the composition further comprises a second antigen.  
     
     
         10 . A method for the prevention or treatment of a disease in a subject comprising administering to the subject an immunologically effective dose of an antigen adjuvanted with a non-toxic mutant as defined in any one of  claims 2  to  5  by contacting a mucosal surface of the subject with said adjuvanted antigen.  
     
     
         11 . A method according to  claim 10  comprising administration of a composition according to any one of  claims 1  to  5 .  
     
     
         12 . A method according to  claim 11  or  claim 12 , wherein the adjuvanted antigen is administered orally or intranasally.  
     
     
         13 . A non-toxic mucosal adjuvant and a second antigen for simultaneous separate or sequential administration.  
     
     
         14 . A non-toxic mucosal adjuvant and a second antigen for simultaneous administration when combined in a single vehicle, carrier or particle.  
     
     
         15 . A method for the manufacture of an adjuvanted vaccine comprising the steps of: 
 a) performing site-directed mutagenesis on the A-subunit of a bacterial ADP-ribosylating toxin in order to detoxify the toxin; and    b) bring the detoxified toxin into association with a second antigen, such that it functions as a mucosal adjuvant.