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The Clinical-Grade 42-Kilodalton Fragment of Merozoite Surface Protein 1 of Plasmodium falciparum Strain FVO Expressed in Escherichia coli Protects Aotus nancymai against Challenge with Homologous Erythrocytic-Stage Parasites

Christian A. Darko ,^1,, Evelina Angov,^1*, William E. Collins,² Elke S. Bergmann-Leitner,¹ Autumn S. Girouard,¹ Stacy L. Hitt,¹ Jana S. McBride,³ Carter L. Diggs,⁴ Anthony A. Holder,⁵ Carole A. Long,⁶ John W. Barnwell,² and Jeffrey A. Lyon¹

Department of Immunology, Walter Reed Army Institute of Research, Silver Spring,¹ Malaria Vaccine Development Unit, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland,⁶ Division of Parasitic Diseases, Centers for Disease Control and Prevention, Chamblee, Georgia,² USAID Malaria Vaccine Development Program, U.S. Agency for International Development, Washington, D.C.,⁴ School of Biological Sciences, University of Edinburgh, Edinburgh, Scotland,³ Division of Parasitology, National Institute for Medical Research, London, United Kingdom⁵

Received 2 July 2004/ Returned for modification 9 August 2004/ Accepted 20 September 2004

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 MSP1₄₂ gene fragment from the Vietnam-Oak Knoll (FVO) strain of Plasmodium falciparum was expressed as a soluble protein in Escherichia coli and 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 against P. falciparum malaria 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 vaccinating Aotus nancymai monkeys and challenging them with homologous P. falciparum FVO erythrocytic-stage malaria parasites. The trial included two control groups, one vaccinated with the sexual-stage-specific antigen of Plasmodium 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 by E. coli MSP1₄₂ were significantly higher than those induced by the baculovirus-expressed antigen. None of the six monkeys that were vaccinated with the E. coli MSP1₄₂ antigen 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 MSP1₄₂ protein itself or the EGF-like domain 1 fragment. Soluble MSP1₄₂ (FVO) expressed in E. coli offers excellent promise as a component of a vaccine against erythrocytic-stage falciparum malaria.

Editor: W. A. Petri, Jr.

C.D. and E.A. contributed equally to this work.

Present address: Department of Cellular Injury, Walter Reed Army Institute of Research, Silver Spring, MD 20910.

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