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 overall focus of this research has been to optimize the design, composition and formulation of malaria Modular Chimeric Vaccines (MCVs) as effective intervention measures to control the disease in endemic areas. MCVs are synthetic genes designed to express an array of protective antigens derived from several proteins and a number of Plasmodium universal T cell epitopes. Malaria parasites'universal T cell epitopes will promote helper T-cell responses, overcome the genetic restriction associated with several malaria antigens and facilitate the boosting effect induced by natural exposure to malaria parasites. MCVs are designed to induce immune responses to several stages of the parasite life cycle. Our rigorous evaluation of MCVs in stringent models of protection will provide critical data to advance the development of this vaccine platform for use in clinical trials. Relevance: malaria caused by P. vivax is a major worldwide health problem with an estimated 80 million cases annually. Outside Africa, P. vivax is the most widely distributed malaria parasite. P. vivax malaria is resurging and now represents a serious threat in areas where it had been eradicated. The emergence of P. vivax chloroquine and primaquine drug resistant strains has brought increased emphasis to the need for alternative prophylactic and therapeutic strategies to control this infection. During this period proof of principle studies, using the rodent malaria parasite P. yoelii, have been completed. Three chimeric proteins designed to cover two different stages of the parasite development have been tested for efficacy in mice. Two additional MCVs designed for P. vivax have been also expressed and purified during this period and preliminary biological characterization has been completed. These experiments open the way to study vaccine efficacy of MCVs in non-human primate models of malaria.
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