This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The broad long-term objective of this project is to develop Plasmodium vivax merozoite surface protein-3 (PvMSP-3) and PvMSP-9 recombinant proteins as candidate malaria vaccine products.
The specific aims of the proposed studies are to: 1) Optimize the expression of PvMSP-3 and PvMSP-9 full-length and partial gene constructs in bacterial or yeast expression systems to obtain appropriate products for further testing of these antigens as malaria vaccine candidates; 2) Identify natural immunogenic B and T cell epitopes in PvMSP-3 and PvMSP-9 by evaluating currently available blood samples from individuals with different levels of exposure to P. vivax malaria infections in endemic areas of Brazil; 3) Evaluate immune responses in mice and rabbits, generated against several PvMSP-3 and PvMSP-9 candidate vaccine containing B and T cell epitopes formulated in clinical grade adjuvants; and 4) Test the safety, immunogenicity and efficacy of selected PvMSP-3 and PvMSP-9 candidate vaccine formulations in non-human primates.
This research aims to produce up to three candidate products that can be evaluated for vaccine efficacy in New World monkeys. The most promising products will also be tested in rhesus macaques for safety and immunogenicity in order to judge the potential for producing adequate responses in human clinical studies. These combined approaches will help to identify the most efficacious PvMSP-3 and PvMSP-9 vaccine immunogens. This proposal will advance the development of several P. vivax vaccine candidates based on these antigens and also serve to establish reliable procedures to test and evaluate antigens in non-human primate models for safety, immunogenicity and efficacy.
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