Development, characterization and immunogenicity of a multi-stage, multi-valent Plasmodium falciparum vaccine antigen (FALVAC-1A) expressed in Escherichia coli.
A synthetic multistage, multi-epitope Plasmodium falciparum malaria antigen (FALVAC-1A) was designed and evaluated in silico, and then the gene was constructed and expressed in Escherichia coli. The FALVAC-1A protein was purified by inclusion body isolation, followed by affinity and ion exchange chromatography. Although FALVAC-1A was a synthetic antigen, it folded to a specific, but as yet incompletely defined, molecular conformation that was stable and comparable from lot to lot. When formulated with four different adjuvants, FALVAC-1A was highly immunogenic in rabbits, inducing not only ELISA reactivity to the cognate antigen and most of its component epitopes, but also in vitro activity against P. falciparum parasites as demonstrated by inhibition of sporozoite invasion, antibody dependent cellular inhibition and the immunofluorescence assay.
Zhou
Zhiyong
Z
Division of Parasitic Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia 30341, USA. zaz6@cdc.gov
Todd
Charles W
CW
Wohlhueter
Robert M
RM
Price
April
A
Xiao
Lihua
L
Schnake
Paul
P
Bonner
Phillip Cullison
PC
Martin
Amy M
AM
Goldman
Ira F
IF
De La Vega
Patricia
P
Udhayakumar
Venkatachalam
V
Lal
Altaf A
AA
D000595:Amino Acid Sequence; D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood / Q000276:immunology; D000953:Antigens, Protozoan / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism*; D017780:Malaria Vaccines / Q000276:immunology*; D016778:Malaria, Falciparum / Q000517:prevention & control; D010963:Plasmodium falciparum / Q000276:immunology*; D011817:Rabbits
D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D017780:Malaria Vaccines