Malaria Transmission Blocking Vaccine Discovery

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In order to develop a transmission blocking vaccine (TBV) against P. falciparum and P. vivax, LMIV has focused on antigen discovery to identify new targets of TBV, as well as evaluation of different platforms particularly protein-protein conjugation to enhance immunogenicity of known antigens. Antigen discovery has focused on using human serum samples collected from individuals that are naturally exposed to malaria, and who appear to develop effective immunity that prevents gametocytemia, or that blocks parasite transmission to mosquitoes, as tools to identify candidate vaccine antigens. Specifically, serum samples that have activity of interest, are compared to sera that lack this activity, for their ability to select or recognize individual recombinant proteins constructs in P. falciparum expression libraries. Recombinant proteins identified through differential screening are tyhen prepared as immunogens and tested for their ability to induce effective anti-gametocyte or transmission blocking antibodies. Improvement of immunogenicity projects have focused on chemical conjugation of recombinant proteins from P. falciparum or their orthologues from P. vivax, to protein carriers. The monomeric proteins and conjugates thereof are being evaluated in animal studies for functional activity and immune enhancement, respectively and the antisera are being evaluated for transmission blocking activities in mosquitoes.