NDLI: 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

Content Provider	PubMed Central
Author	Stanisic, Danielle I. Martin, Laura B. Liu, Xue Q. Jackson, David Cooper, Juan Good, Michael F.
Copyright Year	2003
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 (MSP119) 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 yMSP119-specific antibodies. While synthetic peptides derived from MSP119 are immunogenic in B10.S mice, they cannot function as helper epitopes, and immunization with yMSP119 does not induce T cells that recognize the recombinant protein or synthetic peptides corresponding to its sequence. Nonresponsiveness could be overcome by using chemical linkers to conjugate yMSP119 to diphtheria toxoid (DT), resulting in immunogens capable of inducing protective yMSP119-specific antibodies in both MSP119-responsive and otherwise nonresponsive mouse strains. The ability of sera from mice immunized with the conjugate to inhibit binding of a protective monoclonal antibody (MAb 302) to yMSP119 correlated strongly with a delay in the prepatent period. Chemical conjugation of yMSP119 to DT may be a preferred method to enhance immunogenicity, as carrier priming experiments demonstrated that an existing immune response to DT enhanced a subsequent antibody response to yMSP119 after vaccination with yMSP119-DT. These results have important implications for the development of a malaria vaccine to protect a population with diverse HLAs.
Related Links	http://dx.doi.org/10.1128/IAI.71.10.5700-5713.2003
Starting Page	5700
File Format	PDF
ISSN	10985522
e-ISSN	10985522
Journal	Infection and Immunity
Issue Number	10
Volume Number	71
Language	English
Publisher	American Society for Microbiology
Publisher Date	2003-10-01
Access Restriction	Open
Rights Holder	American Society for Microbiology
Subject Keyword	Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Infectious Diseases Parasitology Immunology Microbiology

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