Development and pre-clinical analysis of a Plasmodium falciparum Merozoite Surface Protein-1(42) malaria vaccine |
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Authors: | Angov Evelina Aufiero Barbara M Turgeon Ann Marie Van Handenhove Michel Ockenhouse Christian F Kester Kent E Walsh Douglas S McBride Jana S Dubois Marie-Claude Cohen Joe Haynes J David Eckels Kenneth H Heppner D Gray Ballou W Ripley Diggs Carter L Lyon Jeffrey A |
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Affiliation: | Department of Immunology, WRAIR, 503 Robert Grant Avenue, Silver Spring, MD 20910, USA. Evelina.Angov@na.amedd.army.mil |
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Abstract: | Merozoite Surface Protein-1(42) (MSP-1(42)) is a leading vaccine candidate against erythrocytic malaria parasites. We cloned and expressed Plasmodium falciparum MSP-1(42) (3D7 clone) in Escherichia coli. The antigen was purified to greater than 95% homogeneity by using nickel-, Q- and carboxy-methyl (CM)-substituted resins. The final product, designated Falciparum Merozoite Protein-1 (FMP1), had endotoxin levels significantly lower than FDA standards. It was structurally correct based on binding conformation-dependent mAbs, and was stable. Functional antibodies from rabbits vaccinated with FMP1 in Freund's adjuvant inhibited parasite growth in vitro and also inhibited secondary processing of MSP-1(42). FMP1 formulated with GlaxoSmithKline Biologicals (GSK) adjuvant, AS02A or alum was safe and immunogenic in rhesus (Macaca mulatta) monkeys. |
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