IMMUNOGENICITY AND IN-VIVO EFFICACY OF RECOMBINANT PLASMODIUM-FALCIPARUM MEROZOITE SURFACE PROTEIN-1 IN AOTUS MONKEYS

Background: The carboxy-terminus of the merozoite surface protein-1 (M SP1) of Plasmodium falciparum has been implicated as a target of prote ctive immunity. Materials and Methods: Two recombinant proteins from t he carboxy-terminus of MSP1, the 42 kD fused to GST (bMSP1(42)) and th e 19 kD (yMSP1(19)), were expressed in Escherichia coli and secreted f rom Saccharomyces cerevisiae, respectively. To determine if vaccinatio n with these recombinant proteins induces protective immunity, we cond ucted a randomized, blinded vaccine trial in two species of Aotus monk eys, A. nancymai and A. vociferans. After three injections using Freun d's adjuvant, the monkeys were challenged with the virulent Vietnam Oa k Knoll (FVO) strain of P. falciparum. Results: All three control monk eys required treatment by Day 19. Two of three monkeys vaccinated with bMSP1(42) required treatment by Day 17, whereas the third monkey cont rolled parasitemia for 28 days before requiring treatment. In contrast , both of the A. nancymai vaccinated with yMSP1(19) self-resolved an o therwise lethal infection. One of the two yMSP1(19)-vaccinated A. vaci ferans had a prolonged prepatent period of >28 days before requiring t reatment. No evidence of mutations were evident in the parasites recov ered after the prolonged prepatent period. Sera from the two A. nancym ai that self-cured had no detectable effect on in vitro invasion. Conc lusions: Vaccination of A. nancymai with yMSP1(19) induced protective immune responses. The course of recrudescing parasitemias in protected monkeys suggested that immunity is not mediated by antibodies that bl ock invasion. Our data indicate that vaccine trials with the highly ad apted FVO strain of P. falciparum can be tested in A. nancymai and tha t MSP1(19) is a promising anti-blood-stage vaccine for human trials.