With improved financial and technical supports, many malaria endemic nations are once again considering a goal of malaria elimination. However, this ambitious goal is met with tremendous technical difficulties especially in regions where Plasmodium vivax is prevalent. Interruption of malaria transmission worldwide has been recognized as one of the greatest challenges in malaria elimination. Vaccines that interrupt malaria transmission are ideally suited to this task. However, the progress in development of transmission blocking vaccines (TBVs) has been very slow. To date, we only have a few TBV immunogens with compelling evidence of transmission blocking activities. For P. vivax, TBV studies lag even behind and only two post-fertilization antigens Pvs25 and Pvs28 have been studied. Therefore, this application targets the serious deficiency of knowledge about pre-fertilization stage antigens in the neglected P. vivax parasite using systematic approaches including antigen discovery in rodent malaria parasites, validation of transmission blocking activities in P. vivax, and development of novel vaccine delivery tools. We aim to 1) identify new sexual stage antigens and evaluate their transmission blocking potentials in the rodent malaria parasite P. berghei; 2) validate known pre-fertilization TBV candidates and newly identified candidates using fresh P. vivax clinical isolates; and 3) improve transmission blocking activities of antigens by expressing the antigens in a baculovirus surface display system and by using a TBV combination strategy targeting both pre- and post-fertilization antigens simultaneously. Results from these comprehensive studies will contribute to increased knowledge about TBV development, which is urgently needed for the ultimate elimination of vivax malaria. PUBLIC HEALTH RELEVANCE: This project seeks to use the rodent malaria parasite as a model for initial screening of new transmission blocking vaccine candidates, which will be further validated in the human malaria parasite Plasmodium vivax. Identification and evaluation of transmission blocking vaccines against vivax malaria parasite are urgently needed for the impending malaria elimination campaigns.