Immune gene expression changes more during a malaria transmission season than between consecutive seasons.

Plasmodium parasites caused over 600,000 deaths in 2022. In Mali, P. falciparum is responsible for the majority of malaria cases and deaths and is transmitted seasonally. Anti-malarial immunity develops slowly over repeated exposures to P. falciparum but some aspects of this immunity (e.g., antibody titers) wane during the non-transmission, dry season. Here, we sequenced RNA from 33 pediatric blood samples collected during P. falciparum infections at the beginning or end of a transmission season and characterized the host and parasite gene expression profiles of paired, consecutive infections. Our analyses showed that human gene expression changes more over the course of one transmission season than it does between seasons, with signatures consistent with the partial development of adaptive immunity during one transmission season, contrasting with the stability in gene expression during the dry season. By contrast, P. falciparum gene expression did not seem to vary significantly and remained stable both across and between seasons. Overall, our results provide novel insights into the dynamics of anti-malarial immunity development over short timeframes.