Diverse and weakly immunogenic var gene expression facilitates malaria infection

These genes undergo mutually exclusive expression and encode the PfEMP1 surface antigen. The frequency of var switching and the immunogenicity of each expressed PfEMP1 remain unclear.

To this end, we carried out a Controlled Human Malaria Infection (CHMI) study with 19 adult African volunteers in The Gambia to gain insight into the effect of naturally acquired immunity on the expressed var gene repertoire during early phase of an infection. Our findings demonstrated a strong correlation between the diversity of var expression, quantified through entropy, and infection outcome. Low-immunity individuals were characterised by high var entropy profiles, higher parasitaemia, and lower sero-recognised PfEMP1 domains compared to high-immunity individuals.