SYNTHETIC POLYPEPTIDES CORRESPONDING TO THE NON-REPEAT REGIONS FROM THE CIRCUMSPOROZOITE PROTEIN OF PLASMODIUM-FALCIPARUM - RECOGNITION BY HUMAN T-CELLS AND IMMUNOGENICITY IN OWL MONKEYS

Synthetic polypeptides encompassing the non-repeated regions of the ci rcumsporozoite protein (CSP) of Plasmodium falciparum are very immunog enic in mice and are recognized by sera from donors living in regions where malaria is endemic, both in Africa and South America. Long polyp eptides, encompassing the N- or C-terminal regions, have now been used to demonstrate peptide-specific T cells in donors living in an endemi c area of Colombia. Although the N-terminal peptide (22-125) was recog nized almost exclusively by donors from the endemic area, the patterns of recognition of the C-terminal peptide (289-390) in donors from end emic and non-endemic areas were similar and like the pattern with smal ler peptides. The availability of the long polypeptides made it possib le to compare T-cell responses to the non-repeated regions of the CSP with the presence of peptide-specific antibodies. No correlation was f ound and no antibodies were detected in donors from non-endemic region s. The long polypeptides also elicited strong antibody and T-cell resp onses in owl monkeys (Aotus lemurinus). The antibodies generated again st the synthetic peptides in such monkeys also recognized sporozoites, the natural infective form of the parasite. The results emphasise the potential of the peptides tested as malaria-vaccine candidates. Not o nly are they recognized by humans at both the B- and T-cell level but they also elicit strong responses in monkeys and encompass several dis tinct T-cell epitopes, thus overcoming the limitations of specific, ma jor-histocompatibility-complex restriction.