A RECOMBINANT BACULOVIRUS 42-KILODALTON C-TERMINAL FRAGMENT OF PLASMODIUM-FALCIPARUM MEROZOITE SURFACE PROTEIN-1 PROTECTS AOTUS MONKEYS AGAINST MALARIA

The immunogenicity and protective efficacy of a baculovirus recombinan t polypeptide based on the Plasmodium falciparum merozoite surface pro tein 1 (MSP-1) has been evaluated in Aotus lemurinus griseimembra monk eys. The MSP-1-based polypeptide, BVp42, corresponds to the 42-kDa C-t erminal processing fragment of the precursor molecule, Immunization of Aotus monkeys,vith BVpl2 in complete Freund's adjuvant resulted in hi gh antibody titers against the immunogen as well as parasite MSP-1. Fi ne specificity studies indicated that major epitopes recognized by the se antibodies localize to conserved determinants of the 19-kDa C-termi nal fragment derived from cleavage of the 42-kDa processing fragment, Effective priming of MSP-1-specific T cells was also demonstrated in l ymphocyte proliferation assays, All three Aotus monkeys immunized with BVp42 in complete Freund's adjuvant showed evidence of protection aga inst blood-stage challenge with P. falciparum. Two animals were comple tely protected, with only one parasite being detected in thick blood f ilms on a single day after infection. The third animal had a modified course of infection, controlling its parasite infection to levels belo w detection by thick blood smears for an extended period in comparison with adjuvant control animals, All vaccinated, protected Aotus monkey s produced antibodies which inhibited in vitro parasite growth, indica ting that this assay may be a useful correlate of protective immunity and that immunity induced by BVp42 immunization is mediated, at least in part, by a direct effect of antibodies against the MSP-1 C-terminal region. The high level of protection obtained in these studies suppor ts further development of BVp42 as a candidate malaria vaccine.