Development and pre-clinical analysis of a Plasmodium falciparum Merozoite Surface Protein-1(42) malaria vaccine.
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.
Department of Immunology, WRAIR, 503 Robert Grant Avenue, Silver Spring, MD 20910, USA. Evelina.Angov@na.amedd.army.mil
Evelina
E
Angov
Barbara M
BM
Aufiero
Ann Marie
AM
Turgeon
Michel
M
Van Handenhove
Christian F
CF
Ockenhouse
Kent E
KE
Kester
Douglas S
DS
Walsh
Jana S
JS
McBride
Marie-Claude
MC
Dubois
Joe
J
Cohen
J David
JD
Haynes
Kenneth H
KH
Eckels
D Gray
DG
Heppner
W Ripley
WR
Ballou
Carter L
CL
Diggs
Jeffrey A
JA
Lyon
D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D004353:Drug Evaluation, Preclinical; D005260:Female; D008253:Macaca mulatta; D017780:Malaria Vaccines / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D016778:Malaria, Falciparum / Q000517:prevention & control; D008297:Male; D020066:Merozoite Surface Protein 1 / Q000145:classification / Q000276:immunology*; D008957:Models, Genetic; D008969:Molecular Sequence Data; D010963:Plasmodium falciparum / Q000254:growth & development / Q000276:immunology*; D011817:Rabbits; D014614:Vaccines, Synthetic / Q000737:chemistry / Q000235:genetics / Q000276:immunology
D000913:Antibodies, Protozoan; D017780:Malaria Vaccines; D020066:Merozoite Surface Protein 1; D014614:Vaccines, Synthetic