Conjugates of plasmodium falciparum surface proteins as malaria vaccines

Abstract

Conjugates of ookinete surface protein Pfs25 are provided that are efficacious as vaccines against Plasmodium falciparum , the most severe form of malaria. Conjugates of ookinete surface protein Pvs25 for use as a vaccine against Plasmodium vivax are also provided. Methods for preparing the conjugates, which comprise the ookinete surface protein bound onto itself or onto another protein by a linking group, are also provided.

1 . A conjugate comprising a first protein that comprises a  Plasmodium vivax  surface protein Pfs25 bound to a second protein that comprises a  Plasmodium vivax  surface protein Pvs25, or a  Pseudomonas aeruginosa  recombinant exoprotein A. 
     
     
         2 .- 41 . (canceled) 
     
     
         42 . The conjugate of  claim 1 , wherein said second protein comprises a  Plasmodium falciparum  surface protein Pvs25. 
     
     
         43 . The conjugate of  claim 1 , wherein said second protein comprises a  Pseudomonas aeruginosa  recombinant exoprotein A. 
     
     
         44 . The conjugate of  claim 1 , having the formula: 
       
         
           
           
               
               
           
         
       
       wherein n is an integer of from 3 to 5, X 1  is a  Plasmodium vivax  surface protein Pfs25, and X 2  is a  Plasmodium vivax  surface protein Pvs25 or a  Pseudomonas aeruginosa  recombinant exoprotein A. 
     
     
         45 . The conjugate of  claim 44 , wherein n is 4. 
     
     
         46 . The conjugate of  claim 44 , wherein X 2  is a  Plasmodium falciparum  surface protein Pvs25. 
     
     
         47 . The conjugate of  claim 1 , having the formula: 
       
         
           
           
               
               
           
         
       
       wherein p is an integer of from 1 to 3, q is an integer of from 1 to 3, r is 1 to 2, X 1  is a  Plasmodium vivax  surface protein Pfs25, and X 2  is a  Plasmodium falciparum  surface protein a  Plasmodium vivax  surface protein Pvs25 or a  Pseudomonas aeruginosa  recombinant exoprotein A. 
     
     
         48 . The conjugate of  claim 47 , wherein p is 2, q is 2, and r is 1. 
     
     
         49 . The conjugate of  claim 47 , wherein X 1  is a  Plasmodium falciparum  surface protein Pfs25 and X 2  is a  Plasmodium falciparum  surface protein Pvs25. 
     
     
         50 . A pharmaceutical composition for eliciting transmission-blocking activity of antibodies to a  Plasmodium  in a host, comprising:
 a conjugate of  claim 1 ; and   a pharmaceutically acceptable excipient.   
     
     
         51 . The pharmaceutical composition of  claim 50 , further comprising an adjuvant. 
     
     
         52 . The pharmaceutical composition of  claim 51 , wherein the adjuvant is aluminum hydroxide. 
     
     
         53 . A method of inducing an immune response to a Malaria antigen in a mammal comprising:
 providing the conjugate of  claim 1  to said mammal; and measuring the immune response of said mammal.