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

## TL;DR

This study explores how antibodies in Ugandan children and adults can block the transmission of malaria parasites by targeting sexual-stage antigens.

## Contribution

The study reveals the natural dynamics of transmission-reducing antibodies and their association with specific sexual-stage antigens in a longitudinal cohort.

## Key findings

- TRA occurs naturally and may persist in some individuals over time.
- Antibodies against Pfs48/45 and Pfs230 predict high-level TRA.
- Antibodies against thirteen other sexual-stage antigens are linked to high-level TRA.

## Abstract

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.