Antibody DNA Vaccine Against Malaria

The overall goal of this proposal is to validate a new principle and method of immunization against the malaria parasite, gen immunization using as a vaccine an immunoglobulin gene re-engineered to encode a discrete epitope of the malaria parasite. We refer to this approach as "antigenization of antibody". As a model system we will use the tetrapeptide sequence Asn-Ala-Asn Pro (NANP) of the malaria parasite Plasmodium falciparum CS protein. Recently, we obtained evidence that immunization with a plazmid DNA encoding the wild type immunoglobulin heavy chain polypeptide combined with targeting of the lymphoid tissue elicits an antiimmunoglobulin response direct at both the constant and variuable portion of the molecule. Moreover, following DNA immunization the gene product appears in the circulation for a period of approximately 10 days in quantifialbe amounts. Previosly, we demonstrated that an antiboldy antigenized to express three contiguous repeats of the NANP epitope could be used to induce antibodies reacting wit P. falciparum sporozoites, a NANP synthetic peptide, and the immunizing antigenized antibodies, and that these atnibodies could inhibit sporozoite invasion of human hepatoma cells in vitro. In the studies proposed her we intend to use plasmid DNA for the heavy chain of an antigenized antibody encoding for (NANP)3 to immunize mice and induce an anti-P. falciparum antibody response specific for the NANP peptide. The studies are designed at verifying feasibility and empirically establishing a series of parameters such as specificity and titer of the antibody response, isotype of NANP-reactive antibodies, duration of the antibody response and priming effect on a subsequent immune response elecited by a protein antigen. We are excited hy this new approach and hopeful that the ensemble of results that will be generated in the proposed work will constitute the permise for future and wider spectrum investigations on the potential use of antigenized antibody DNA immunization against malaria parasite in humans.