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

Abstract

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.