Cross-species reactivity of antibodies against Plasmodium vivax blood-stage antigens to Plasmodium knowlesi

Malaria is caused by multiple different species of protozoan parasites, and interventions in the pre-elimination phase can lead to drastic changes in the proportion of each species causing malaria. In endemic areas, cross-reactivity may play an important role in the protection and blocking transmission. Thus, successful control of one species could lead to an increase in other parasite species. A few studies have reported cross-reactivity producing cross-immunity, but the extent of cross-reactive, particularly between closely related species, is poorly understood. P . vivax and P . knowlesi are particularly closely related species causing malaria infections in SE Asia, and whilst P . vivax cases are in decline, zoonotic P . knowlesi infections are rising in some areas. In this study, the cross-species reactivity and growth inhibition activity of P . vivax blood-stage antigen-specific antibodies against P . knowlesi parasites were investigated. Bioinformatics analysis, immunofluorescence assay, western blotting, protein microarray, and growth inhibition assay were performed to investigate the cross-reactivity. P . vivax blood-stage antigen-specific antibodies recognized the molecules located on the surface or released from apical organelles of P . knowlesi merozoites. Recombinant P . vivax and P . knowlesi proteins were also recognized by P . knowlesi- and P . vivax -infected patient antibodies, respectively. Immunoglobulin G against P . vivax antigens from both immune animals and human malaria patients inhibited the erythrocyte invasion by P . knowlesi . This study demonstrates that there is extensive cross-reactivity between antibodies against P . vivax to P . knowlesi in the blood stage, and these antibodies can potently inhibit in vitro invasion, highlighting the potential cross-protective immunity in endemic areas.