A Chimeric Plasmodium vivax Merozoite Surface Protein Antibody Recognizes and Blocks Erythrocytic P. cynomolgi Berok Merozoites <i>In Vitro</i>

Abstract

Research on erythrocytic <i>Plasmodium vivax</i> merozoite antigens is critical for identifying potential vaccine candidates in reducing <i>P. vivax</i> disease. However, many <i>P. vivax</i> studies are constrained by its inability to undergo long-term culture <i>in vitro</i> Conserved across all <i>Plasmodium</i> spp., merozoite surface proteins are essential for invasion into erythrocytes and highly expressed on erythrocytic merozoites, thus making it an ideal vaccine candidate. In clinical trials, the <i>P. vivax</i> merozoite surface protein 1 (PvMSP1-19) vaccine candidate alone has shown to have limited immunogenicity in patients; hence, we incorporate the highly conserved and immunogenic C terminus of both <i>P. vivax</i> merozoite surface protein 8 (PvMSP8) and PvMSP1-19 to develop a multicomponent chimeric protein rPvMSP8+1 for immunization of mice. The resulted chimeric rPvMSP8+1 antibody was shown to recognize native protein MSP8 and MSP1-19 of mature <i>P. vivax</i> schizonts. In the immunized mice, an elevated antibody response was observed in the rPvMSP8+1-immunized group compared to that immunized with single-antigen components. In addition, we examined the growth inhibition of these antibodies against <i>Plasmodium cynomolgi</i> (Berok strain) parasites, which is phylogenetically close to <i>P. vivax</i> and sustains long-term culture <i>in vitro</i> Similarly, the chimeric anti-rPvMSP8+1 antibodies recognize <i>P. cynomolgi</i> MSP8 and MSP1-19 on mature schizonts and showed strong inhibition <i>in vitro</i> via growth inhibition assay. This study provides support for a new multiantigen-based paradigm rPvMSP8+1 to explore potential chimeric vaccine candidates against <i>P. vivax</i> malaria using sister species <i>P. cynomolgi</i>.