The murine malarial parasite P. yoelii 17X is a model system which clearly requires the production of antibody by the infected host for resolution of infection. We have constructed a monoclonal antibody (McAb 302) which provides dramatic protection from a lethal P. yoelii 17XL challenge, even in the antibody is given after infection. We propose to use this antibody as a probe to investigate a number of aspects of the murine humoral response to malarial infection. Our primary studies will involve determining the biological role of the idiotype represented by McAb 302. This will be approached by the generation of anti-idiotypic antibody to the 302 idiotype, leading to the development of a specific 302 idiotype assay. This assay will be used to compare the kinetics of appearance and concentration of these antibodies in a variety of protective and nonprotective sera. The in vivo regulatory role of anti-idiotypic antibodies will be explored by passive transfer of anti-idiotypic antibody. We also propose to examine the possible role of the unusual IgG3 isotype in the biological activity of McAb 302. Finally, we will isolate and study the major 230kd plasmodial antigen recognized by this antibody with particular attention to identification of significant epitopes. These studies will define more critically the biological role of antibodies to a protective plasmodial molecule and particularly those antibodies of the 302 idiotype. If the constraints are severe on the idiotype, isotype, or concentration of antibodies that must be attained to give protection, then this has significant consequences for human vaccination programs.
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