Molecular Characterization of Recombinant Plasmodium falciparum PHISTB Proteins as Potential Targets of Naturally Acquired Immunity against Malaria in Humans

Abstract

Plasmodium falciparum is known to cause the deadliest form of malaria in sub-Saharan Africa. Upon infection, remodeling of infected host red blood cells (iRBCs) by parasite-exported surface proteins occurs providing a favorable niche for parasite development and maturation. Some of these molecules include products of the multi-copy family of Plasmodium helical interspersed sub-telomeric (PHIST) proteins, whose role in malaria pathogenesis largely remains unknown at present. In a recent transcriptome analysis of clinical isolates, some members of PHISTb gene family were associated with parasite adaptations to malaria transmission intensity and gametocyte development. To characterize the possibility of these proteins as potential vaccine targets, recombinant proteins were expressed in bacteria followed by ELISA-based evaluation of antibody responses using immune sera from malaria-exposed individuals. Our findings show that children and adults from malaria-endemic region recognized PHISTb proteins, Pf3D7_0532400, Pf3D7_1401600, and Pf3D7_1102500, providing a clinical evidence for the role of PHISTb antigens in immune response against Plasmodium falciparum infection. Antibody responses against the three recombinant PHISTb antigens were however variable. An association study of antibody responses to the different PHISTb antigens with age revealed no correlation between the age and antibody responses to Pf3D7_1102500 and Pf3D7_1401600 (p=0.507 and p=0.15, respectively, CI=95%), but a significant correlation to Pf3D7_0532400 (p=0.009). Furthermore, there was strong correlation of antibody responses to both the crude schizont extract and Pf3D7_0532400 (p=0.005), equivalent to those against Pf3D7_1102500 and Pf3D7_1401600 (p=0.0001). It was further established that immune responses to recombinant PHISTb proteins was varied depending on malaria transmission intensities in three different geographical sites in Kenya (Siaya, Takaungu) and The Gambia (Sukuta). Collectively, these findings empirically provide evidence of recombinant PHISTb antigens as potential targets of naturally acquired immunity against malaria in humans and possible serological markers to P. falciparum infection aimed at contributing to malaria control through vaccine development.