BACULOVIRUS MEROZOITE SURFACE PROTEIN-1 C-TERMINAL RECOMBINANT ANTIGENS ARE HIGHLY PROTECTIVE IN A NATURAL PRIMATE MODEL FOR HUMAN PLASMODIUM-VIVAX MALARIA

A successful anti-blood stage malaria vaccine trial based on a leading vaccine candidate, the major merozoite surface antigen-1 (MSP1), is r eported here, The trial was based on Plasmodium cynomolgi, which is a primate malaria parasite which is highly analogous to the human parasi te Plasmodium vivax, in its natural host, the toque monkey, Macaca sin ica, Two recombinant baculovirus-expressed P. cynomolgi MSP1 proteins, which are analogous to the 42- and 19-kDa C-terminal fragments of P.f alciparum MSP1, were tested by immunizing three groups of three animal s each with either p42, p19, or both together, The vaccines were deliv ered subcutaneously in three doses at 4-week intervals with complete a nd incomplete Freund's adjuvants, Very high antibody titers were obtai ned against both vaccinating antigens as measured by enzyme-linked imm unosorbent assay (10(6) and above) and against whole parasites as meas ured by indirect immunofluorescence assay (>10(5)), achieving, in most animals, about a 10-fold increase from the first to the last immuniza tion, A blood stage challenge with P. cynomolgi parasites led, in thre e adjuvant-treated and three naive control animals, to blood infection s which were patent for at least 44 days, reaching peak densities of 0 .6 and 3.8%, respectively, In contrast, all except one of the nine ani mals in the three vaccinated groups were highly protected, shelving ei ther no parasitemia at all or transient parasitemias which were patent for only 1 or 2 days, When the three p19-vaccinated monkeys were rech allenged 6 months later, the protective efficacy was unchanged, The su ccess of this trial, and striking analogies of this natural host-paras ite system with human P. vivax malaria, suggests that it could serve a s a surrogate system for the development of a human P, vivax malaria v accine based on similar recombinant analogs of the P. vivax MSP1 antig en.