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.
Angov
Evelina
E
Department of Immunology, WRAIR, 503 Robert Grant Avenue, Silver Spring, MD 20910, USA. Evelina.Angov@na.amedd.army.mil
Aufiero
Barbara M
BM
Turgeon
Ann Marie
AM
Van Handenhove
Michel
M
Ockenhouse
Christian F
CF
Kester
Kent E
KE
Walsh
Douglas S
DS
McBride
Jana S
JS
Dubois
Marie-Claude
MC
Cohen
Joe
J
Haynes
J David
JD
Eckels
Kenneth H
KH
Heppner
D Gray
DG
Ballou
W Ripley
WR
Diggs
Carter L
CL
Lyon
Jeffrey A
JA
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