The kinetics and transmission-blocking dynamics of P. 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 transmission when ingested during a mosquito’s blood meal. This study aims to unravel the immune signature and longitudinal dynamics of naturally occurring transmission reducing activity (TRA). Using data from 611 standard membrane feeding assays and up to 18 assessments per individual, we show that TRA occurs naturally and may persist over time in a minority of naturally exposed individuals. We also show that history of asymptomatic parasite exposure is positively related to TRA and to antibodies against P. falciparum sexual-stage antigens. Antibodies against Pfs48/45 and Pfs230 appeared relatively short-lived and predicted high-level TRA. Finally, we find that naturally acquired antibodies against thirteen other sexual-stage antigens (including Pfs47, Pf77, PfHAP2 and PfMDV1) were associated with high-level TRA. Together, our analysis shows that naturally acquired sexual-stage immune responses are dynamic and can inhibit onward parasite transmission.