Sara Lynn Blanken, Patience Nayebare, Jonathan Briese, Gerine Nijman, Karina Teelen, Rianne Stoter, Geert-Jan van Gemert, Wouter Graumans, Tate Oulton, Catriona Patterson, Abdoulie Drammeh, Marloes de Bruijni, Judith Bolscher, Lauren M Cohee, Sanjai Kumar, Noah Sather, Alvaro Molina-Cruz, Emmanuel Arinaitwe, Moses R Kamya, Koen Dechering, Grant Dorsey, Chris Drakeley, Matthijs M Jore, Teun Bousema, William Stone
Individuals naturally infected with Plasmodium can develop antibodies against the parasite's sexual stages that may inhibit onward transmission when ingested they are during a mosquito vector's blood meal. Our study reports immune signatures and longitudinal dynamics of naturally occurring transmission-reducing activity (TRA) in a Ugandan cohort. Combining data from 611 standard membrane feeding assays and up to 18 assessments per individual, we show that TRA arose naturally and persisted in a minority of naturally exposed individuals. We also show that prior history of parasite exposure is positively related to both TRA and antibodies against P. falciparum sexual-stage antigens. Antibodies against Pfs48/45 and Pfs230 appeared relatively short-lived and associated with high-level TRA. Finally, we report that naturally acquired antibodies against a further thirteen sexual-stage antigens are associated with high-level TRA. Together, our analysis shows that naturally acquired sexual-stage immune responses are dynamic and can inhibit onward parasite transmission.