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

Abstract

Abstract. Saimiri boliviensis monkeys were immunized with the yeast-expressed recombinant 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 Plasmodium vivax Salvador I strain. Two universal T helper cell epitopes (P 2 and P 30 ) 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 250 g of yP 2 P 30 Pv200 19 formulated with nonionic block copolymer P1005, 250 g of antigen adsorbed to alum, 250 g 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 P 30 Pv200 19 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 testing 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 parasite and the nonhuman primate model of Saimiri boliviensis boliviensis. [1][2][3][4][5][6][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 prepatent 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 ) of P. 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 ...

Merozoite Surface Protein 1 of Plasmodium vivax Induces a Protective Response against Plasmodium cynomolgi Challenge in Rhesus Monkeys

“…The results of this study clearly indicate the ability of MSP-1 42 with Montanide ISA720 to induce a partially protective immune response in primates using an adjuvant acceptable for human use instead of FCA. Similar partial protection has been reported in two other challenge trials using PvMSP-1 19 and a nonionic block copolymer in the splenetomized Saimiri monkey model against P. vivax challenge (45,11).…”

Antigenicity, Immunogenicity, and Protective Efficacy of Plasmodium Vivax Msp1 Pv200l: A Potential Malaria Vaccine Subunit

“…4 Because antibodies specific to this protein, particularly to the C-terminal region (42-kD and 19-kD subfragments), have been shown to block parasite invasion in vitro [5][6][7] and to induce protective immunity in animal models, [8][9][10][11][12][13] this MSP-1 fragment has long been considered a major vaccine candidate. 12,14,15 Limited effort has been invested in the definition and testing of other MSP-1 fragments as potential vaccine candidates.…”

Purification, Characterization, and Immunogenicity of a Disulfide Cross-Linked Plasmodium vivax Vaccine Candidate Antigen, Merozoite Surface Protein 1, Expressed in Escherichia coli

“…It has been shown in rodent models of malaria that the presence of the two epidermal growth factorlike domains in the p19 region is critical for the induction of MSP-1-based protective immunity (19,20). In addition, it has been shown that immunization with recombinant P. vivax MSP-1 p19 made in baculovirus-infected insect cells can protect monkeys against parasite challenge (6,30). Although the p33 region has not been shown to be critical for protection, several immunodominant B-and T-cell epitopes have been mapped to it; these epitopes are highly immunogenic during natural malaria infection in humans (10).…”