Malaria transmission-blocking vaccines (TB) represent a potential tool to control malaria in areas of low malaria endemicity. Since TB responses to P. vivax have been demonstrated in malaria endemic areas, we propose to first evaluate the existence of such responses in communities from a P. vivax malaria endemic area of Colombia and will to study the TM response of Aotus monkeys infected experimentally or immunized with TBV candidates. We plan to study the potential blockage of P. vivax by the presence of circulating specific antibodies in P. vivax infected individuals. These studies will be performed by artificial-membrane feeding of mosquitoes with whole and serum-depleted blood of donor from endemic areas (aim1). If natural TB is observed, we will attempt to characterize the targets of this immune response by analyzing the specificity of the blocking antibodies. Second, since it has been demonstrated that P. falciparum antigens homologous to P. vivax Pvs25 and Pvs28 antigens (Pvs25/28) are capable of inducing parasite transmission blocking antibodies, we propose to focus on the study of their role in natural induction of TB and the potential to induce TB antibodies in Pvs25/28 immunized Aotus monkeys. Sera of individuals from endemic areas, including those that may have displayed TB activity will be studied for the presence of specific antiPvs 25/28. The presence of such antibodies in endemic communities will suggest the expression of these antigens in parasite blood stages (aim 2). Due to the potential of these antigens as vaccine candidates, we will further evaluate the extension of their expression during the parasite life cycle and will characterize the relevant epitopes and functional domains. Once such epitopes are defined, the presence and extent of polymorphism will be assessed (aim 3). These studies will allow the establishment at this TMRC of the Aotus model system to study the immunogenicity and protective efficacy of P. vivax TBV candidates.
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