The Clinical-Grade 42-Kilodalton Fragment of Merozoite Surface Protein 1 ofPlasmodium falciparumStrain FVO Expressed inEscherichia coliProtectsAotus nancymaiagainst Challenge with Homologous Erythrocytic-Stage Parasites

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Abstract
A 42-kDa fragment from the C terminus of major merozoite surface protein 1 (MSP1) is among the leading malaria vaccine candidates that target infection by asexual erythrocytic-stage malaria parasites. The MSP142gene fragment from the Vietnam-Oak Knoll (FVO) strain ofPlasmodium falciparumwas expressed as a soluble protein inEscherichia coliand purified according to good manufacturing practices. This clinical-grade recombinant protein retained some important elements of correct structure, as it was reactive with several functional, conformation-dependent monoclonal antibodies raised againstP. falciparummalaria parasites, it induced antibodies (Abs) that were reactive to parasites in immunofluorescent Ab tests, and it induced strong growth and invasion inhibitory antisera in New Zealand White rabbits. The antigen quality was further evaluated by vaccinatingAotus nancymaimonkeys and challenging them with homologousP. falciparumFVO erythrocytic-stage malaria parasites. The trial included two control groups, one vaccinated with the sexual-stage-specific antigen ofPlasmodium vivax, Pvs25, as a negative control, and the other vaccinated with baculovirus-expressed MSP142(FVO) as a positive control. Enzyme-linked immunosorbent assay (ELISA) Ab titers induced byE. coliMSP142were significantly higher than those induced by the baculovirus-expressed antigen. None of the six monkeys that were vaccinated with theE. coliMSP142antigen required treatment for uncontrolled parasitemia, but two required treatment for anemia. Protective immunity in these monkeys correlated with the ELISA Ab titer against the p19 fragment and the epidermal growth factor (EGF)-like domain 2 fragment of MSP142, but not the MSP142protein itself or the EGF-like domain 1 fragment. Soluble MSP142(FVO) expressed inE. colioffers excellent promise as a component of a vaccine against erythrocytic-stage falciparum malaria.

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