Analysis of immunological nonresponsiveness to the 19-kilodalton fragment of merozoite surface protein 1 of Plasmodium yoelii: Rescue by chemical conjugation to diphtheria toxoid (DT) and enhancement of immunogenicity by prior DT vaccination

Abstract

The Plasmodium merozoite surface protein 1 (MSP1) is a leading vaccine candidate for protecting against the blood stage of malaria. Previous studies have shown that the 19-kDa carboxyl terminus of this protein is able to induce protective immunity in some monkey and mouse strains. We show that immunization with the recombinant Plasmodium yoelii 19-kDa fragment of MSP1 (MSP1 19) expressed in Saccharomyces cerevisiae (yMSP119) can induce protective antibodies in several inbred mouse strains and one outbred mouse strain. However, mice expressing the H-2s major histocompatibility complex haplotype are unable to generate yMSP1 19-specific antibodies. While synthetic peptides derived from MSP119 a..