Effect of GPI anchor moiety on the immunogenicity of DNA plasmids encoding the 19-kDa C-terminal portion of Plasmodium falciparum MSP-1

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The glycosylphosphatidylinositol(GPI)-anchored Plasmodium falciparumd merozoite surface protein 1 (MSP-1) is a widely studied malaria vaccine candidate. The C-terminal 19-kDa portion of MSP-1 (MSP-119) is of particular interest because this polypeptide moiety remains bound to the parasite even after erythrocyte invasion, while the remainder of MSP-1 is shed during invasion. Studies have shown that antibodies against MSP-119 inhibit merozoite invasion of erythrocytes efficiently, and that MSP-119 produces protective immunity in mice and monkeys. To investigate the efficacy of MSP-119DNA vaccine and role of GPI anchor moiety in the immunogenicity of MSP-119, we constructed expression vectors that produce MSP-119 as either secretory or GPI-anchored polypeptide. Both constructs efficiently expressed MSP-119 in transfected HEK-293 cells.While the recombinant plasmid lacking GPI anchor signal sequence expressed MSP-119 mainly as secreted polypeptide, that containing GPI anchor signal sequence produced GPI-anchored MSP-119on cell surface. In immunized mice, both constructs produced substantial levels of MSP-119-specific IgG1, IgG2a, IgG2b, IgG3, IgA and IgM antibodies. In both cases, the IgG1 level was significantly higher than other isotypes.Interestingly, the plasmid containing GPI anchor signal sequence produced significantly higher levels of IgG2a and IgG2b than the plasmid that lacks GPI signal sequence.

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