Immune response against a novel Plasmodium vivax erythrocyte binding protein (EBP2) in a Brazilian naturally exposed population

Background: Recently, a new member of the Duffy binding protein family was discovered in Plasmodium vivax– named Erythrocyte binding protein 2 (EBP2) – and this protein may play a role as a ligand mediating an alternative invasion pathway for young Duffy-positive reticulocytes (Ntumngia et al., MBio. e01261-16, 2016). Inindividuals naturally exposed to malaria in the Amazon region, we investigated the antibody response against EBP2 and their relationship to antibodies induced by the Duffy Binding Protein (DBPII), the major ligand involved in P.vivax reticulocyte invasion. Methods: An open cohort study was carried among 425 volunteers (median age: 23 years) from a native Amazonian community with long-term P.vivax exposure. ELISA-detected IgG antibodies were evaluated by using recombinant proteins based on ligand-domain of EBP2 and DBPII. The study design included five cross-sectional surveys, three carried-out during the first year (baseline, 6 and 12 months), and two 6 and 7 years later. Results: Taken together, the results demonstrated that (1) during the first follow-upyear, the frequencies of anti-EBP2 (60-70%) was higher that frequencies of anti-DBPII (20-36%); (2) Six to 7 years later, at the time that malaria transmission had declined dramatically in the study area, the profile of EBP2 antibody response remained relatively stable while DBPII antibodies dropped significatively. Conclusion: As compared with DBPII, EBP2 is highly immunogenic and induces a long-term immune response. Further studies should investigate whether antibodies against EBP2 are able to block reticulocytes P.vivax invasion.