Plasmodium sexual stage parasites present distinct targets for malaria transmission-blocking vaccine design

Malaria is an infectious disease that in humans is caused by one of five species of the protozoan parasite Plasmodium and which is transmitted by mosquitoes of the genus Anopheles. Despite much investment over many years to eradicate or control the global incidence of malaria, infection remains a major cause of morbidity and mortality throughout the world, particularly in developing countries in tropical and subtropical regions. A large number of candidate vaccines has been developed against different antigens expressed by separate life cycle stages of Plasmodium. Transmission-blocking vaccines (TBVs) aim to combat the sexual stages of parasite development that occur distinctively inside the mosquito vector. This also has a potentially significant impact on the efficacy of other malaria vaccines which target stage-specific antigens expressed within humans by reducing the spread of parasites in the community, an altruistic approach that leads to a local herd immune response. In 1958 the first successful steps towards producing a TBV used an avian model to raise sexual stage-specific antibodies. In the almost 60 years that have elapsed since this proof of principle demonstration considerable effort has been expended in order to identify parasite antigens the expression of which elicits transmission-blocking activity. This review considers the significance of an anti-malaria TBV strategy, the range of potential targets, and the incremental advances which have been made to produce effective TBVs.