Targeting Prohibitin 2-Hsp70A1A complex during Plasmodium falciparum invasion of erythrocytes as a novel approach towards vaccine candidacy

Abstract Malaria parasite invade human erythrocytes in the merozoite stage that contribute towards the development of disease pathology. Invasion is mediated by multiple interactions between merozoite ligands and erythrocyte receptors. Here, we report a novel interaction of Plasmodium prohibitin ‘PfPHB2’ with human Hsp70A1A that plays a crucial role in mediating host-parasite interaction during merozoite invasion to RBCs. Using siRNA and glmS mediated approach, we show that loss of Hsp70A1A or PfPHB2 function blocks parasite growth owing to the inability of merozoites to invade erythrocytes. Antibodies targeting PfPHB2 or Hsp70A1A efficiently block parasite invasion in vitro that reiterate that PfPHB2 - Hsp70A1A complex facilitates merozoite invasion to new erythrocytes. Inhibition of recombinant PfPHB2 binding to RBCs in the presence of anti-PfPHB2/anti-Hsp70A1A antibodies, and patient sera from malaria infected individuals provide additional evidence for PfPHB2 participation in host–parasite interactions. Interestingly, PfPHB2 was found to generate a strong humoral response in malaria patients that illustrate the immunogenicity of this surface protein and its importance as vaccine candidate. Based on our results, we propose a novel attribute of Plasmodium PHB2 and anti-Hsp70A1A monoclonal antibody that can be combinedly used to design future approaches targeting PfPHB2-Hsp70A1A interaction in the parasite.