Development, Characterization and Immunogenicity of a Multi-Stage, Multivalent Plasmodium falciparum Vaccine Antigen (FALVAC-1A) Expressed in Escherichia coli

Abstract

A synthetic multistage, multi-epitope Plasmodium falciparum malaria antigen(FALVAC-1A) was designed and evaluated in silico, and then the gene wasconstructed and expressed in Escherichia coli. The FALVAC-1A protein waspurified by inclusion body isolation, followed by affinity and ion exchangechromatography. Although FALVAC-1A was a synthetic antigen, it folded to aspecific, but as yet incompletely defined, molecular conformation that was stableand comparable from lot to lot. When formulated with 4 different adjuvants,FALVAC-1A was highly immunogenic in rabbits, inducing not only ELISAreactivity to the cognate antigen and most of its component epitopes, but also invitro activity against P. falciparum parasites as demonstrated by inhibition ofsporozoite invasion, antibody dependent cellular inhibition and theimmunofluorescence assay.