Transmission-blocking vaccine (TBV) for malaria

This application focuses on a TBV that targets a mosquito midgut surface protein, the Anopheline Alanyl aminopeptidase N (AnAPN1), which mediates Plasmodium establishment in the mosquito (9, 13). Our recent
studies demonstrate that anti-APN1 antibodies completely block (100% inhibition) the development of naturally circulating isolates of Plasmodium falciparum in Cameroon across replicate infections using infected blood collected from gametocytemic volunteers from two independent transmission seasons (5). The mechanism of action of TBVs in general is restricted solely to the activity of inhibitory antibodies (5, 14, 15). Therefore, the objective of a successful TBV is to induce potent, high-titer antibodies in an appropriate proportion of the population, sustainable for at least one transmission season or ideally greater than 1 year. However, the traditional multiple vaccine dose schedule, coupled with inadequate immune stimulation and the lack of natural boosting, poses a serious challenge to effective delivery of such a vaccine. An ideal TBV formulation for use in malaria endemic regions would be a single dose vaccine that is capable of eliciting potent and long-lasting protection