The parasitic disease malaria is a leading cause of morbidity and mortality globally, with over 250 million cases and approximately 600,000 deaths reported in 2024. Elimination has stalled over the past decade, highlighting an urgent need for new tools and interventions such as efficacious vaccines. Plasmodium vivax is responsible for a large burden of malaria outside of Africa including Southeast Asia. However, no licensed P. vivax vaccines exist, and few candidates are under development. Developing P. vivax vaccines is challenging due to the absence of continuous in vitro parasite culture. Merozoite surface proteins (MSPs) on the infective blood stage merozoite are promising vaccine candidates as they are exposed to the immune system, particularly antibodies. Investigating the functions of antibodies to MSPs is essential to understanding key immune mechanisms and identifying promising vaccine candidates.
In a study of P. vivax exposed Papua New Guinean children and rabbits immunised with recombinant P. vivax MSPs, we evaluated the ability of antibodies to induce multiple protective functional antibody responses to whole merozoites and six P. vivax MSPs. To overcome challenges in P. vivax culture, we used the phylogenetically closely related and culture adapted P. knowlesi. P. knowlesi merozoites and recombinant P. vivax MSP antigens were targets of multiple P. vivax functional antibody activities, including Fcγ receptor (FcγRIa, IIa and III) binding and complement fixation with activity varying between antigens. Downstream antibody Fc-dependent effector functions opsonic phagocytosis was seen for all MSPs and strongly correlated with FcγR-binding while antibody dependent cellular cytotoxicity varied between antigens.
This work further validates P. knowlesi as a model for studying P. vivax immunity and highlighted cross-reactivity between the two species. Additionally, we provide novel insights into P. vivax immunity and identify P. vivax MSPs that are targets of multiple potent protective functional antibody responses and potential vaccine candidates.