SYNTHETIC PEPTIDES AS CARRIERS FOR CONJUGATE VACCINES.

THE LONG TERM OBJECTIVE OF THIS RESEARCH IS TO GENERATE BACTERIAL CAPSULAR POLYSACCHARIDE-PEPTIDE CONJUGATE VACCINESTHAT WILL PROTECT INFANTS, WHO UNLIKE OLDER CHILDREN AND ADULTS, CAN NOT PRODUCE ANTIBODIES TO POLYSACCHARIDE ANTIGENS. CONJUGATE VACCINES THAT ARE UNDER DEVELOPMENT IN DIFFERENT COMPANIES USING INTACT PROTEINS AS CARRIERS FOR POLYSACCHARIDES WILL OFFER PROTECTION TO INFANTS IN THE IMMEDIATE FUTURE. HOWEVER, THE COMPLEX AND UNKNOWN CHARACTERISTICS OF CARRIER PROTEINS MAY INDUCE SIDE REACTIONS THAT WILL BE AGGREVATED WHEN MULTIPLE CONJUGATE VACCINES WITH THE SAME CARRIER PROTEINS ARE PREPARED. THIS PROPOSAL IS AIMED AT PRODUCING WELL DEFINED SYNTHETIC CONJUGATE VACCINES BY COVALENTLY COUPLING PRP FROM HEMOPHILUS INFLUENZAE TO SYNTHETIC PEPTIDES CORRESPONDING TOT CELL EPITOPE OF CRM(197). T CELL EPITOPE OF CRM (PRIMARILY RESIDUES 357-380) WILL BE COUPLED TO PRP BY PERIODATE OXIDATION AND REDUCTIVE AMINATION PROCEDURES. THE CONJUGATES WILL BE CHARACTERIZED IN T AND B CELL STIMULATION ASSAY. THE IMMUNOGENICITY WILL BE EVALUATED BY VACCINATING CARRIER PRIMED MICE WITH CONJUGATE VACCINES. THESE SYNTHETIC CONJUGATE VACCINES CAN BE PRODUCED COST EFFECTIVELY FOR COMMERCIAL PURPOSES. THE CARRIER PEPTIDE CAN BE POTENTIALLY CONJUGATED TO DIFFERENT POLYSACCHARIDES AND ANTIGENIC PEPTIDES FROM PARASITES, VIRUSAND OTHER BACTERIA IN ORDER TO PRODUCE SYNTHETIC CONJUGATE VACCINES.