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 recombinant protein yP2P30Pv20019. The antigen consisted of the C-terminus (amino acid Asn1622-Ser1729) of the merozoite surface protein 1o f thePlasmodium vivax Salvador I strain. Two universal T helper cell epitopes (P 2 and P30) of tetanus toxin and six histidine residues for purification purposes were attached to the N- and C-termini, respectively. Four groups of five monkeys were given three immunizations at four-week intervals with either 250m go f yP 2P30Pv20019 formulated with nonionic block copolymer P1005, 250 mg of antigen adsorbed to alum, 250 mg of antigen in phosphate-buffered saline (PBS), or PBS alone. Five weeks after the last immunization, each animal was inoculated with 100,000 parasitized erythrocytes of the Salvador I strain of P. vivax. Animals were splenectomized one week after 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 protected from rechallenge. One monkey immunized with yP 2 P30Pv20019 with alum was protected; no protection was seen after rechallenge. Two monkeys immunized with antigen alone were protected; none were protected from rechallenge. One control animal had a low parasite count following primary infection; none were protected against rechallenge. Adverse reactions were only observed with animals receiving P1005. It is proposed that splenectomy of the monkeys prevented adequate assessment of the efficacy of this antigen. Identification of a monkey host that supports high density parasitemia without splenectomy appears needed before further testing of blood-stage vaccines against P. vivax. Procedures are being developed and evaluated for the test- ing of different synthetic peptide and recombinant protein vaccines in animals susceptible to infection with different species of Plasmodium. A model system has been developed for the testing of vaccines directed against the sporozoites of Plasmodium vivax using the Salvador I strain of the par- asite and the nonhuman primate model of Saimiri boliviensis boliviensis. 1-7 In previous trials, immunized animals were challenged with 10,000 or more sporozoites dissected from the salivary glands of infected mosquitoes, and the animals were splenectomized one week after challenge to increase parasitemia. Infection rate was highly predictable, but pre- patent periods varied markedly. Our present study was designed to determine if this model system could be used to test the efficacy of a recombinant vaccine directed against the merozoite surface protein (MSP- 1 19 )o fP. vivax. To increase uniformity of parasitemia, all animals were challenged by the intravenous inoculation of parasitized erythrocytes. All animals were splenectomized seven or eight days after challenge. Included in the trial were two adjuvants, a nonionic block copolymer P1005, previ- ously shown to increase antibody responses,