title: Merozoite surface protein 1 of Plasmodium vivax induces a protective response against Plasmodium cynomolgi challenge in rhesus monkeys.
abstract: The 42-kDa fragment of the merozoite surface protein 1 (MSP-1(42)) is a leading candidate for the development of a vaccine to control malaria. We previously reported a method for the production of Plasmodium vivax MSP-1(42) (PvMSP-1(42)) as a soluble protein (S. Dutta, L. W. Ware, A. Barbosa, C. F. Ockenhouse, and D. E. Lanar, Infect. Immun. 69:5464-5470, 2001). We report here a process to manufacture the same PvMSP-1(42) protein but as an insoluble inclusion body-derived protein which was then refolded in vitro. We compared the immunogenicity and protective efficacy of the soluble and refolded forms of PvMSP-1(42) protein by using a heterologous but closely related P. cynomolgi-rhesus monkey challenge model. As comparative controls we also expressed, purified, and immunized rhesus with the soluble and refolded forms of the P. cynomolgi MSP-1(42) (PcMSP-1(42)) proteins. All proteins induced equally high-titer, cross-reacting antibodies. Upon challenge with P. cynomolgi, none of the MSP-1(42)-vaccinated groups demonstrated sterile protection or a delay in the prepatent period. However, following an initial rise in parasitemia, all MSP-1-vaccinated animals had significantly lower parasite burdens as indicated by lower cumulative parasitemia, lower peak parasitemia, lower secondary peak parasitemia, and lower average daily parasitemia compared to the adjuvant control group (P < 0.05). Except the soluble PcMSP-1(42) group, monkeys in all other groups had fewer numbers of days with parasitemia of >10,000 parasites mm(-3). Interestingly, there was no significant difference in the level of partial protection observed in the homologous and heterologous groups in this challenge model. The soluble and refolded forms of PcMSP-1(42) and PvMSP-1(42) proteins also appeared to have a similar partially protective effect.
authors.affiliation: Department of Immunology, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.
authors.forename: Sheetij
authors.initials: S
authors.lastname: Dutta
authors.forename: Deep C
authors.initials: DC
authors.lastname: Kaushal
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Ware
authors.forename: Sunil K
authors.initials: SK
authors.lastname: Puri
authors.forename: Nuzhat A
authors.initials: NA
authors.lastname: Kaushal
authors.forename: Atul
authors.initials: A
authors.lastname: Narula
authors.forename: D S
authors.initials: DS
authors.lastname: Upadhyaya
authors.forename: David E
authors.initials: DE
authors.lastname: Lanar
mesh_terms: D000818:Animals; D008253:Macaca mulatta; D008288:Malaria / Q000097:blood / Q000276:immunology / Q000517:prevention & control*; D017780:Malaria Vaccines / Q000276:immunology*; D020066:Merozoite Surface Protein 1 / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D008969:Molecular Sequence Data; D016789:Plasmodium cynomolgi / Q000276:immunology*; D010966:Plasmodium vivax / Q000276:immunology*; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification; D017422:Sequence Analysis, DNA
chemical_list: D017780:Malaria Vaccines; D020066:Merozoite Surface Protein 1; D011994:Recombinant Proteins