EXPRESSION OF MALARIA CSP ANTIGEN IN RECOMBINANT HERPESVIRUS

MALARIA IS ONE OF THE MOST IMPORTANT PARASITIC DISEASES OF MAN. IT IS CAUSED BY SPECIES OF THE PROTOZOAN PLASMODIUM WHICH HAVE A COMPLEX LIFE CYCLE OF SEVERAL DEVELOPMENTAL STAGES THAT OCCUR IN BOTH MAN AND THE INSECT VECTOR ANOPHELINE MOSQUITO. RECENTLY, SEVERAL PLASMODIUM GENES HAVE BEEN CLONED THAT HAVE BEEN SHOWN TO CODE FOR ANTIGENS PRESENTED BY BOTH SPOROZOITES AND MEROZOITES. THESE ANTIGENS HAVE BEEN EXPRESSED IN BACTERIA AND SOME OF THEM WILL SOON BE UNDERGOING CLINICAL TRIALS AS CANDIDATES FOR SUBUNIT VACCINES. SYNTRO HAS DEVELOPED THE TECHNOLOGY FOR ATTENUATING HERPESVIRUSES AND FOR USING THESE VIRUS VECTORS FOR THE EXPRESSION OF FOREIGN GENES. IN THIS PHASE I APPLICATION WE PROPOSE TO EXPRESS THE CIRCUMSPOROZOITE SURFACE ANTIGEN (CSP) OF P.FALCIPARUM IN RECOMBINANT PSEUDORABIES OF SWINE. THE ENGINEERED VIRUS WILL BE INOCULATED INTO WEANLING PIGS AND THE PRODUCTION OF ANTI-CSP ANTIBODY WILL BE ASSAYED. POSITIVE RESULTS WILL INDICATE THAT THIS APPROACH IS FEASIBLE FOR THE DEVELOPMENT OF A MALARIA VACCINE FOR HUMANS AND WILL LEAD TO A PHASE II APPLICATION TO DEVELOP A HUMAN VACCINE USING A RECOMBINANT HERPERSVIRUS AS A VECTOR.