Blocking the cycle: Antimalarial and immunisation strategies to target Plasmodium falciparum transmission

Malaria remains a major global health challenge, with Plasmodium falciparum responsible for most morbidity and mortality. This thesis explores strategies to reduce malaria transmission through both drug- and antibody-based interventions. In three phase 2 clinical trials in Mali, we evaluated how different antimalarial regimens influence gametocyte carriage and infectiousness to mosquitoes, demonstrating variable transmission-reducing activity across artemisinin-based and non-artemisinin combination therapies, and highlighting the potential of adding low-dose gametocytocidal drugs such as primaquine or tafenoquine. We further assessed the transmission-blocking vaccine candidate R0.6C and the monoclonal antibody TB31F in first-in-human studies, showing that both are safe and immunogenic, with TB31F providing potent and long-lasting functional activity. A life cycle assessment of a malaria clinical trial quantified its environmental footprint, identifying key contributors and mitigation strategies. Finally, a phase 1 study of the SARS-CoV-2 vaccine candidate ABNCoV2 provided the first clinical evaluation of the modular capsid virus-like particle (cVLP) platform, demonstrating its safety, tolerability, and immunogenicity in humans. Collectively, these studies advance integrated and sustainable strategies to block Plasmodium falciparum transmission and support malaria elimination.