Interventions to interrupt transmission of malaria parasites from humans to mosquitos, including vaccines, represent appealing approaches to support malaria elimination and ultimate eradication. Development of vaccines to interrupt transmission of Plasmodium parasites is complicated by the lack of a methodology to reliably test the efficacy of such interventions before proceeding to field trials, and the absence of data to support that direct membrane feeding assays (DMFA) effectively predict direct skin feeding (DFA).  Evaluation of vaccine-induced, transmission-blocking antibodies using direct skin feeding in endemic settings is complex, requiring naturally acquired infection (uncontrolled) and immunization with a candidate vaccine (controlled) to be aligned.  Evaluation of transmission endpoints, under completely controlled conditions (i.e., controlled human malaria infection, or CHMI), could support early clinical decision-making.

The primary aim of the CHMI-trans project is to develop a CHMI transmission model (CHMI-trans) or “challenge model” to evaluate the capacity of vaccines, biologics (monoclonal antibodies, or mAbs), and drugs to block malaria parasite transmission by assessing infectiousness of Plasmodium falciparum gametocyte carriers for Anopheles mosquitoes.
The key objectives of the project are to:
  1. Adapt the existing CHMI model to safely induce stable gametocytemia at densities detectable by microscopy, with high levels of mature male and female gametocytes in permissible sex ratios, as assessed by quantitative polymerase chain reaction.
  2. Evaluate the infectivity of gametocytes in CHMI-trans model for Anopheles mosquitoes using DMFA and DFA.
  3. Test the CHMI-trans protocol to confirm that the model is sufficiently sensitive to measure the transmission-blocking activity of a candidate vaccine or mAb.