An abundant merozoite surface protein ofPlasmodium falciparummodulates susceptibility to inhibitory antibodies

Malaria merozoite surface proteins (MSPs), are thought to have important roles in red blood cell (RBC) invasion and their exposure on the parasite surface makes them attractive vaccine candidates. However, their role in invasion has not been directly demonstrated and their biological functions are unknown. One of the most abundant proteins isPfMSP2, which is likely an ancestral protein that has been maintained in thePlasmodium falciparumlineage and is a focus of vaccine development, whose function remains unknown. Using CRISPR-Cas9 gene-editing, we removedPfMSP2 from two differentP. falciparumlines with no impact on parasite replication or phenotypein vitro, demonstrating that it is not essential for RBC invasion. However, loss ofPfMSP2 led to increased inhibitory potency of antibodies targeting other merozoite proteins involved in invasion, particularlyPfAMA1. In a solid-phase model, increasing concentrations ofPfMSP2 protein reduced binding of different antibodies againstPfAMA1 in a dose dependent manner. These data suggest thatPfMSP2 can modulate the susceptibility of merozoites to protective inhibitory antibodies. The results of this study change our understanding of the potential functions ofPfMSP2 and establishes a new concept in malaria where a surface protein can reduce the protective efficacy of antibodies targeting a different antigen. These findings have important implications for understanding malaria immunity and informing vaccine development.