Targeting Prohibitin 2-Hu-Hsp70A1A complex as a unique approach towards malaria vaccine development

Malaria parasite invasion to host erythrocytes is mediated by multiple interactions between merozoite ligands and erythrocyte receptors that contribute toward the development of disease pathology. Here, we report a novel antigen prohibitin "PHB2" and identify its cognate partner "Hsp70A1A" in host erythrocyte that plays a crucial role in mediating host-parasite interaction during merozoite invasion. Using small interfering RNA (siRNA)- and glucosamine-6-phosphate riboswitch (glmS) ribozyme-mediated approach, we show that loss of Hsp70A1A in red blood cells (RBCs) or PHB2 in infected red blood cells (iRBCs), respectively, inhibit PHB2-Hsp70A1A interaction leading to invasion inhibition. Antibodies targeting PHB2 and monoclonal antibody therapeutics against Hsp70A1A efficiently block parasite invasion. Recombinant PHB2 binds to RBCs which is inhibited by anti-PHB2 antibody and monoclonal antibody against Hsp70A1A. The validation of PHB2 to serve as antigen is further supported by detection of anti-PHB2 antibody in patient sera. Overall, this study proposes PHB2 as vaccine candidate and highlights the use of monoclonal antibody therapeutics for future malaria treatment.