Expression and antigenicity of Plasmodium falciparum major merozoite surface protein (MSP1(19)) variants secreted from Saccharomyces cerevisiae.

Four antigenic variants of the 19-kDa carboxy terminal fragment of Plasmodium falciparum merozoite surface protein, MSP1 (MSP1(19)), were expressed in Saccharomyces cerevisiae as a histidine-tagged, secreted polypeptides (rMSP1(19)s). Structural analysis of the rMSP1(19)s indicated that a single amino acid change (E to Q) in the first EGF-like domain of the yeast-secreted rMSP1(19) proteins caused a significant change in their disulfide bond-dependent conformation. The antigenicity of the rMSP1(19)s were qualitatively and quantitatively analyzed by direct and competitive binding ELISAs. The data indicate that conserved and variant B cell determinants of MSP1(19), as well as epitopes that are known targets of protective antibodies, were recreated authentically in the rMSP1(19)s. Secretion of histidine-tagged rMSP1(19)s using the expression system described may be an efficient and effective means of producing a properly folded immunogen for a human vaccine against the blood stages of P. falciparum.