Evaluating a cross-reactive epitope in VAR2CSA as a target of immunity in P. vivax and P. falciparum exposed populations

Research Team:  Uwa Iyamu*, Bernard Tornyigah, Daniel Ferrer Vinals, Bart Hazes, and Stephanie K. Yanow

In pregnancy-associated malaria, Plasmodium falciparum expresses the surface antigen, variant surface antigen 2-chondroitin sulphate A (VAR2CSA) on infected erythrocytes (IE), which mediates the sequestration of IE in the placenta. Protective antibodies to VAR2CSA are acquired following infection with P. falciparum during pregnancy. We discovered that infection with P. vivax can elicit antibodies that cross-react with VAR2CSA. Specifically, a monoclonal antibody (3D10) raised against P. vivax Duffy binding protein (PvDBP) recognizes VAR2CSA. The epitope recognized by 3D10 is mapped to the subdomain 1 (SD1) of region II in PvDBP. However, we do not know the epitopes in VAR2CSA targeted by 3D10.

We screened an array of overlapping peptides spanning VAR2CSA with 3D10 and evaluated one of the reactive peptides, cross-reactive peptide 1 (CRP1), by enzyme-linked immunosorbent assay (ELISA). We tested the ability of CRP1 to block 3D10 recognition of SD1 and VAR2CSA and also determined its antigenicity using 142 sera representing two different Colombian cohorts. CRP1 blocked 3D10 recognition of SD1 and VAR2CSA. More than 50% of both Colombian cohort samples were seroreactive to CRP1, and the reactivity to both CRP1 and SD1 was strongly correlated (rs=0.8424, p<0.0001, n=142). 3D10 targets a shared epitope between CRP1 and SD1, which could explain the strong correlation in the seroreactivity of both antigens. The high frequency of CRP1 antibodies in both Colombian cohorts indicate the natural acquisition of cross-reactive antibodies that target an epitope shared between VAR2CSA and PvDBP. Further experiments are underway to examine the protective benefits of antibodies that target CRP1.

Uwa Iyamu is a third-year doctoral student in Dr. Stephanie Yanow's laboratory at the School of Public Health. He completed his master's degree in Biomedical and Health Science at Monash University, Australia, and his bachelor's program in Biochemistry at the University of Benin, Nigeria. His research focuses on placental malaria and understanding cross-species immunity in malaria.