ANTIGENICITY AND IMMUNOGENICITY OF MULTIPLE ANTIGEN PEPTIDES (MAP) CONTAINING PLASMODIUM-VIVAX CS EPITOPES IN AOTUS MONKEYS

Using linear synthetic peptides corresponding to the Plasmodium vivax circumsporozoite (CS) protein of the common type, we have identified s everal T and B-cell epitopes recognized by human individuals. Three T- cell epitopes studied (p6) from the amino, (pll) from the central and (p25) from the carboxyl regions, were widely recognized by lymphocytes of immune donors. A series of six peptides, in addition to p11, repre senting the central repeat domain of the CS (p11-p17) protein were use d in ELISA assays to map the B-cell epitopes of this region. P11 was t ile peptide most frequently recognized by sera containing antibodies t o the homologous CS protein as determined by IFAT. The sequences corre sponding to peptides p6, pll and P25 as well as that representing a un iversal T-cell epitope derived from the tetanus toxin were used to ass emble eight different Multiple Antigen Peptides (MAP), The immunogenic ity of these MAP was analysed in Aotus monkeys. Groups of two animals were immunized with each MAP and both antibody response, T-lymphocyte proliferation and in vitro gamma-IFN production were evaluated. Two MA Ps containing the same B-cell epitope and either a promiscuous CS-prot ein derived T-cell epitope (p25) or the tetanus toxin epitope (p-tt30) proved to be the most immunogenic and induced high levels of anti-pep tide antibodies that recognized the native protein. Except for animals immunized with MAP VII, there was no correlation between antibody lev els, lymphocyte proliferation or gamma-IFN production in vitro, The br oad recognition of these epitopes by individuals which had been expose d to malaria, the capacity of these MAPs to induce antibodies, recogni ze the cognate protein, and in vitro gamma-IFN production encourages f urther analyses of the potential of these proteins as malaria vaccine candidates for human use.