title: 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.
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 MSP1(42) 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 MSP1(42) (FVO) as a positive control. Enzyme-linked immunosorbent assay (ELISA) Ab titers induced by E. coli MSP1(42) were significantly higher than those induced by the baculovirus-expressed antigen. None of the six monkeys that were vaccinated with the E. coli MSP1(42) 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 MSP1(42), but not the MSP1(42) protein itself or the EGF-like domain 1 fragment. Soluble MSP1(42) (FVO) expressed in E. coli offers excellent promise as a component of a vaccine against erythrocytic-stage falciparum malaria.
authors.affiliation: Department of Immunology, Walter Reed Army Institute of Research, 503 Robert Grant Ave., Silver Spring, MD 20910, USA.
authors.forename: Christian A
authors.initials: CA
authors.lastname: Darko
authors.forename: Evelina
authors.initials: E
authors.lastname: Angov
authors.forename: William E
authors.initials: WE
authors.lastname: Collins
authors.forename: Elke S
authors.initials: ES
authors.lastname: Bergmann-Leitner
authors.forename: Autumn S
authors.initials: AS
authors.lastname: Girouard
authors.forename: Stacy L
authors.initials: SL
authors.lastname: Hitt
authors.forename: Jana S
authors.initials: JS
authors.lastname: McBride
authors.forename: Carter L
authors.initials: CL
authors.lastname: Diggs
authors.forename: Anthony A
authors.initials: AA
authors.lastname: Holder
authors.forename: Carole A
authors.initials: CA
authors.lastname: Long
authors.forename: John W
authors.initials: JW
authors.lastname: Barnwell
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Lyon
mesh_terms: D000818:Animals; D016645:Aotidae; D003001:Cloning, Molecular; D004797:Enzyme-Linked Immunosorbent Assay; D004912:Erythrocytes / Q000469:parasitology*; D004926:Escherichia coli / Q000235:genetics; D017780:Malaria Vaccines / Q000276:immunology*; D020066:Merozoite Surface Protein 1 / Q000235:genetics / Q000276:immunology*; D010963:Plasmodium falciparum / Q000276:immunology*; D011817:Rabbits; D014611:Vaccination; D014614:Vaccines, Synthetic / Q000276:immunology*
chemical_list: D017780:Malaria Vaccines; D020066:Merozoite Surface Protein 1; D014614:Vaccines, Synthetic