Priming or Boosting <i>Plasmodium falciparum</i> Transmission-Blocking Responses With Recombinant Vaccines or Gametocyte Extract

Plasmodium falciparum infection can induce antibody responses to the parasitic, gametocyte-expressed antigens Pfs48/45 and Pfs230. Retrospective analysis of healthy individuals from malaria-endemic Mali showed increasing prevalence of antibodies to these antigens from infancy to age 17 years, an expected response to malaria exposure. This supports examining the immune interplay between gametocyte exposure and vaccination with these antigens as transmission-blocking vaccine (TBV) candidates. Recombinant Pfs48/45 and Pfs230 were formulated with a liposome-display vaccine adjuvant system. In mice primed with either antigen, subsequent gametocyte extract (GE) exposure significantly boosted antibody responses. Dose-dependent GE exposure induced transmission-reducing activity (TRA) in Pfs48/45-primed mice but not in naive controls. Conversely, GE-primed mice exhibited enhanced TRA after Pfs48/45 vaccination. These findings demonstrate bidirectional immune priming and highlight the potential for TBVs to elicit stronger TRA responses upon subsequent natural malaria exposure and/or in endemic areas in individuals with preexisting antibodies to TBV antigens.