PLASMODIUM-FALCIPARUM POLYOXIMES - HIGHLY IMMUNOGENIC SYNTHETIC VACCINES CONSTRUCTED BY CHEMOSELECTIVE LIGATION OF REPEAT B-CELL EPITOPES AND A UNIVERSAL T-CELL EPITOPE OF CS PROTEIN

Effective immunoprophylaxis directed against the pre-erythrocytic stag es of the malaria parasite requires a vaccine that can elicit humoral and cell mediated immunity in individuals of diverse genetic backgroun d. In order for a synthetic peptide malaria vaccine to meet these requ irements, problems associated with genetic restriction, peptide chemis try, adjuvant formulation and physicochemical characterization of the final synthetic vaccine product must first be overcome. To address the se issues, five polyoxime vaccine candidates have been constructed by ligating purified peptide epitopes of the P. falciparum CS protein to a branched template via oxime bonds. All five constructs, including tw o based on templates containing the synthetic adjuvant tripalmitoyl-S- glyceryl cysteine (Pam3Cys), were of sufficient purity for characteriz ation by mass spectrometry. The immunogenicity of the malaria polyoxim es in different murine strains was compared to that of multiple antige n peptide (MAP) constructs synthesized by standard step-wise synthesis . A tri-epitope polyoxime-Pam3Cys construct, based on the repeats and a universal T-cell epitope that contains both helper and CTL epitopes of the CS protein, was shown to be a precisely-defined synthetic malar ia vaccine candidate that was highly immunogenic in murine strains of diverse H-2-haplotypes. (C) 1988 Elsevier Science Ltd. All rights rese rved.