SYNTHETIC VACCINES: TEST OF CONCEPTS AND APPLICATION TO RIFT VALLEY FEVER VIRUS

USE OF SYNTHETIC PEPTIDES, COMPRISING BOTH B AND T CELL DETERMINANTS, IS BEING CONSIDERED A VIABLE APPROACH TO VACCINE DEVELOPMENT. WE WILL EXPLORE THE SUITABILITY OF THIS STRATEGY EMPLOYING RIFT VALLEY FEVER VIRUS (RVFV) AS THE STUDY MODEL. THE IMMUNOGENICITY OF SYNTHETIC PEPTIDES REPRESENTING SEVERAL PREVIOUSLY IDENTIFIED B CELL ANTIGENIC DETERMINANTS ON THE G2 GLYCOPROTEIN OF RVFV WILL BE EVALUATED IN FOUR STRAINS OF MICE DIFFERING IN H-2 HAPLOTYPE. A PEPTIDE SHOWING LOW IMMUNOGENICITY IN AT LEAST SOME MOUSE STRAINS WILL BE SELECTED FOR FURTHER STUDY. THE EFFECT OF KNOWN HELPER T CELL EPITOPES ON THE IMMUNOGENICITY OF THIS B EPITOPE PEPTIDE WILL THEN BE ESTABLISHED. FINALLY, HELPER T CELL SITE PREDICTIVE ALGORITHMS WILL BE TESTED FOR THEIR ABILITY TO IDENTIFY DETERMINANTS FROM THE GLYCOPROTEIN G2 SEQUENCE CAPABLE OF OVERRCOMING THE NONRESPONSIVENESS TO THE ABOVE B CELL EPITOPE. THESE STUDIES WILL EVALUATE SEVERAL CONCEPTS CENTRAL TO SYNTHETIC VACCINE DEVELOPMENT, AND IF VALIDATED, WILL ADVANCE THEIR APPLICATION TOWARD SUCH A VACCINE FOR RVFV.