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

Abstract

Abstract. The merozoite surface protein 1 (MSP-1) is expressed in all Plasmodium species and is considered a major malaria vaccine candidate. We found that MSP-1 from Plasmodium vivax (PvMSP-1) contains a region of significant sequence homology with the 190L subunit vaccine derived from the P. falciparum MSP-1. The fragment, termed Pv200L, was expressed as a recombinant protein in Escherichia coli (rPv200L) and used to asses its immunologic relevance as a vaccine target. A cross-sectional, seroepidemiologic study conducted in Buenaventura, Colombia showed that 52.2% (95% confidence interval [CI] ‫ס‬ 39.8-64.3) of individuals previously exposed to P. vivax and 72.8% (95% CI ‫ס‬ 61.8-82.1) of P. vivax-infected patients had IgG antibodies to rPv200L. Immunization of BALB/c mice and Aotus monkeys induced IgG antibodies (titer > 10 6 ) that cross-reacted with P. vivax parasites. Immunized monkeys displayed partial protection against a challenge with P. vivax blood stages. Our results suggest that Pv200L is a new malaria vaccine subunit and deserves further testing.

Evaluation of Recombinant Plasmodium knowlesi Merozoite Surface Protein-133 for Detection of Human Malaria

“…26 It was further shown that that T cell response and antibodies against MSP1 were induced in human clinical trials by using P. falciparum MSP-1, in which epitopes responsible for cytokine production and memory response development were localized to the 33-kDa region of MSP-1 42 . 27,28 Hitherto, most of the studies on MSP-1 33 have focused on P. falciparum, P. vivax, or P. yoelii, but few on P. knowlesi. A large amount of P. knowlesi MSP-1 33 is required for its biochemical, structural, and immunologic studies.…”

“…27,28 Hitherto, most of the studies on MSP-1 33 have focused on P. falciparum, P. vivax, or P. yoelii, but few on P. knowlesi. A large amount of P. knowlesi MSP-1 33 is required for its biochemical, structural, and immunologic studies. In this study, recombinant MSP-1 33 of P. knowlesi was expressed and purified by using an Escherichia coli system.…”

“…21 MSP-1 42 is one of the leading candidates for blood-stage malaria vaccines because it is able to induce cell-mediated and humoral immune responses, 22 and its proteolytic product MSP-1 33 is responsible for the cellular immune protection. 23 For example, P. yoelii MSP-1 33 induces effector T cells that could assist in protective B cells response and mediate significant antiparasitic activity against P. yoelii. 24,25 Plasmodium falciparum MSP-1 33 is naturally immunogenic because antibodies against this antigen could be detected in serum of P. falciparum-exposed blood donors.…”

“…The first processing cleaves the MSP-1 precursor polypeptide into four major fragments, which are held together on the free merozoite surface by noncovalent contacts. 17,18 The second processing further cleaves one of the fragments (MSP-1 42 ) into two fragments with molecular masses of 33 kDa (MSP-1 33 ) and 19 kDa (MSP-1 19 ). The soluble MSP-1 33 , corresponding to the N-terminal region of MSP-1 42 , sheds from the surface, 19,20 whereas the membranebound MSP-1 19 remains anchored to the merozoite and is carried into the new erythrocyte.…”

“…17,18 The second processing further cleaves one of the fragments (MSP-1 42 ) into two fragments with molecular masses of 33 kDa (MSP-1 33 ) and 19 kDa (MSP-1 19 ). The soluble MSP-1 33 , corresponding to the N-terminal region of MSP-1 42 , sheds from the surface, 19,20 whereas the membranebound MSP-1 19 remains anchored to the merozoite and is carried into the new erythrocyte. 21 MSP-1 42 is one of the leading candidates for blood-stage malaria vaccines because it is able to induce cell-mediated and humoral immune responses, 22 and its proteolytic product MSP-1 33 is responsible for the cellular immune protection.…”