A vaccine to prevent transmission of human malaria: a long way to travel on a dusty and often bumpy road.

摘要

The goal for an effective malaria transmission-blocking vaccine (TBV) is to induce immunity against the stages of the parasite that infect mosquitoes so that malaria transmission can be reduced or halted. Malaria transmission is generally spatially confined to an infectious source, thus a TBV used in a community can effectively suppress malaria transmission to others. Antibodies induced by TBVs target antigens on the surface of sexual and mosquito midgut stages of the malaria parasite and antibodies interfere with the development of the parasites in the midgut of the mosquito. Proteins synthesized in the gametocytes (pre-fertilization antigens, in Plasmodium falciparum: Pfs230 and Pfs48/45) and in the zygotes-ookinetes (post-fertilization antigens, in P. falciparum: Pfs25 and Pfs28) represent some of the key target antigens for the development of TBVs. All the four proteins contain multiple cysteinerich sequences and the epitopes recognized by transmission- blocking antibodies are reduction-sensitive conformational in nature. The inability to express properly folded proteins has frustrated a protein-based TBV development approach and DNA-based vaccine constructs were envisaged to overcome the conformational problem in recombinant proteins. Indeed studies in mice and monkeys have firmly established the value of DNA-based TBV approach. Although immunogenic in larger animals, delivery of DNA-based TBVs needs to be further optimized to elicit a strong and long lasting functional immune response. This DNA vaccine platform can also facilitate evaluation of a cocktail of preand post-fertilization antigens in pre-clinical setting prior to the development of an ideal and effective TBV for clinical trials in human volunteers.