The transmission-blocking dynamics of Plasmodium falciparum sexual-stage antibody responses in a six-year cohort of Ugandan children and adults

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. The study found that naturally acquired immunity that reduces malaria transmission was rare but persistent in a minority of individuals. Transmission reduction was associated with antibodies against gametocyte proteins and with recent parasite exposure.