Malaria invasion ligand RH5 and its prime candidacy in blood-stage malaria vaccine design

Abstract

With drug resistance to available therapeutics continuing to develop against Plasmodium falciparum malaria, the development of an effective vaccine candidate remains a major research goal. Successful interruption of invasion of parasites into erythrocytes during the blood stage of infection will prevent the severe clinical symptoms and complications associated with malaria. Previously studied blood stage antigens have highlighted the hurdles that are inherent to this life-cycle stage, namely that highly immunogenic antigens are also globally diverse, resulting in protection only against the vaccine strain, or that naturally acquired immunity to blood stage antigens do not always correlate with actual protection. The blood stage antigen reticulocyte binding homolog RH5 is essential for parasite viability, has globally limited diversity, and is associated with protection from disease. Here we summarize available information on this invasion ligand and recent findings that highlight its candidacy for inclusion in a blood-stage malaria vaccine.

CRISPR/Cas9 knockouts reveal genetic interaction between strain-transcendent erythrocyte determinants of Plasmodium falciparum invasion

“…A major area of interest in Plasmodium biology has been the identification of essential, strain-transcendent host receptors since their cognate invasion ligands may be potent vaccine candidates (9). We have developed an in vitro culture system for functional analysis of the host contribution to blood-stage P. falciparum invasion using the JK-1 erythroleukemia cell line, which displayed unique features.…”

“…functional characterization of host factors important for parasite invasion. Using this system, we have generated a knockout of the essential host receptor basigin (BSG), for which no natural nulls exist and which binds the parasite invasion ligand Rh5 (23,24), now a leading vaccine candidate (9). We show that the ΔBSGknockout line is completely refractory for parasite invasion, thus validating BSG as an essential receptor for P. falciparum invasion (9,25).…”

“…Invasion of new RBCs occurs rapidly after the release of daughter merozoites from mature schizonts (3), and during the invasion process parasites use multiple invasion ligands to bind to the host RBC by interacting with specific host receptors (4)(5)(6). Blocking these interactions can lead to a reduction in parasite invasion (7), a strategy underlying blood-stage vaccine design (8,9).…”

P113 is a merozoite surface protein that binds the N terminus of Plasmodium falciparum RH5

“…The biochemical interactions involved in invasion are being identified, and their roles in each of these steps determined 4 . Of particular current interest is the interaction between the parasite reticulocyte-binding protein homologue 5 (RH5) and its erythrocyte receptor, basigin 7 .…”

Analysis of factors affecting the variability of a quantitative suspension bead array assay measuring IgG to multiple Plasmodium antigens

“…coli at WRAIR; the liver-stage antigen 1 (LSA-1) [ 30 , 31 ] and the sporozoite surface protein 2 (SSP2 or TRAP) [ 32 , 33 ] expressed in Pichia Pastoris , purchased from Protein Potential, LLC (Rockville, Maryland, USA); and a peptide with 48 aminoacids from the VAR2CSA inter domain 1 region, synthesized by GL Biochem (Shangai, China) [ 34 ]. Based on the readout of the positive control immunogenicities were considered high for AMA-1 and MSP-1 42 , medium for EBA-175 and Rh5 and low for LSA-1 and SSP2 [ 35 , 36 ].…”