Bridging the Knowledge Gap in Transmission-Blocking Immunity to Malaria: Deciphering Molecular Mechanisms in Mosquitoes

The worldwide decline over the last decade in the number of clinical cases of malaria does not mean an end to the universal problem of malaria pathogenesis in those afflicted by infection. Resistance to drugs, higher risk of disease relapse and failure to maintain effective memory of the pathogen in the absence of persistent exposure result in the repeated failure of anti-malarial treatments. The artificial blocking of transmission of the Plasmodium parasite between hosts from human to Anopheles mosquito, and vice versa, is crucial to restricting the spread of disease. However, a limited knowledge of the molecular mechanisms in operation for transmission of malaria has impeded progress towards a transmission-blocking vaccine. This review highlights the role of anti-malarial immune responses to antigen-specific targets for designing effective vaccines against the sexual stages of Plasmodium that occur within the invertebrate vector. In particular, artificial induction of gametocyte and ookinete apoptosis as a novel means to prevent gamete fertilization and oocyte development, respectively, is highlighted. This and other recent insights into our understanding of the molecular regulation of transmission-blocking immunity are discussed and future prospects considered.