Vaccination with purified microgamete antigens prevents transmission of rodent malaria

Malaria vaccination with preparations of microgametes has been shown to inhibit transmission of Plasmodium spp. to the mosquito vectors of avian1,2, rodent3 and simian4,5 parasites. This transmission-blocking immunity results from the induction of microgamete-agglutinating antibodies in the vaccinated host which, when ingested in a mosquito blood meal, react with exflagellating microgametes in the midgut to prevent fertilization and oocyst development. Here we have passively transferred the immunity with gamete-specific monoclonal antibodies raised against the rodent malaria parasite Plasmodium yoelii nigeriensis6, and an IgG2a isotype monoclonal antibody from a hybridoma cell line, PYG-1, has been used to identify the target antigens on the gametes and to affinity-purify sufficient quantities of specific gamete antigen to facilitate vaccination studies. This transmission-blocking monoclonal antibody immunoprecipitated microgamete antigens of apparent relative molecular mass (Mr) 67K (67,000), 59K, 57K, 42K and 35K. Immunization of mice with these proteins before infection and mosquito feeding led to a 85–99.7% reduction in transmission to the mosquito vector; vaccination via intravenous or intramuscular routes was equally effective and did not require an adjuvant.