A whole parasite transmission-blocking vaccine for malaria: an ignored strategy

Malaria vaccine approaches can be divided into 'subunit' and 'whole parasite', and these can be directed at the sporozoite, liver stage, asexual or sexual stages. All combinations of approach and stage are under development with the exception of a whole parasite sexual stage (gametocyte) vaccine. A gametocyte vaccine would aim primarily to block transmission of malaria from the human host to the mosquito vector and as such is referred to as a 'transmission-blocking vaccine'. An immunological feature of whole parasite vaccines for the sporozoite/liver stage and for the asexual blood stage is the reliance on cellular immunity involving T-cells to control parasite growth. T-cells can also respond vigorously to gametocytes and kill them in the vertebrate host and/or arrest their development. To date, cellular immunity has not been exploited in transmission-blocking vaccine development. Here, the data supporting a gametocyte whole parasite vaccine are reviewed and a strategy for vaccine development and testing is outlined.