Testing the efficacy of a recombinant merozoite surface protein (MSP-1(19)) of Plasmodium vivax in Saimiri boliviensis monkeys

Saimiri boliviensis monkeys were immunized with the yeast-expressed recombi nant protein yP(2)P(30)Pv200(19). The antigen consisted of the C-terminus ( amino acid Asn(1622)-Ser(1729)) of the merozoite surface protein 1 of the P lasmodium vivax Salvador I strain. Two universal T helper cell epitopes (P- 2 and P-30) of tetanus toxin and six histidine residues for purification pu rposes were attached to the N- and C-termini, respectively. Four groups of five monkeys were given three immunizations at four-week intervals with eit her 250 mu g of yP(2)P(30)Pv200(19) formulated with nonionic block copolyme r P1005, 250 mu g of antigen adsorbed to alum, 250 mu g of antigen in phosp hate-buffered saline (PBS), or PBS alone. Five weeks after the last immuniz ation, each animal was inoculated with 100,000 parasitized erythrocytes of the Salvador I strain of P. vivax. Animals were splenectomized one week aft er challenge to increase parasite densities; after seven weeks of infection , animals were treated. Eighteen weeks later, the animals were rechallenged with the homologous parasite. Following the first challenge, three monkeys immunized with the antigen with P1005 were protected; no animals were prot ected from rechallenge. One monkey immunized with yP(2)P(30)Pv200(19) with alum was protected; no protection was seen after rechallenge. Two monkeys i mmunized with antigen alone were protected; none were protected from rechal lenge. One control animal had a low parasite count following primary infect ion; none were protected against rechallenge. Adverse reactions were only o bserved with animals receiving P1005. It is proposed that splenectomy of th e monkeys prevented adequate assessment of the efficacy of this antigen. Id entification of a monkey host that supports high density parasitemia withou t splenectomy appears needed before further testing of blood-stage vaccines against P. vivax.