Primary Plasmodium vivax exposure retains long-lasting B-cell memory responses to the Duffy binding protein II

Background: The invasion of erythrocytes by human malaria parasites ensures the success of the infection and, consequently, the development of clinicaldisease. Thus, there is a great interest in the development of vaccines that can induce antibodies able to block parasite invasion. In case of Plasmodium vivax, the main vaccine candidate is the Duffy binding protein II (DBPII), the only known ligand involved in reticulocyte invasion. Although natural acquired DBPII inhibitory antibodies seem to induce protection, it is necessary to evaluate whether this immune response generates long-term humoral immune memory. Here, we investigated antibodies (Abs) and antigen-specific Memory B cells (MBCs) after roughly 12 years of a single and brief exposure to P. vivax malaria infection, occurred during a small outbreak of vivax malaria, in a non-endemic area of Brazil. Materials and Methods: Twenty-five individuals previously exposed to the P. vivax outbreak participated in the study, including those who have had positive or negative thick blood smears at the time of malaria exposure. DBPII -specific MBCs were evaluated by an optimized B-cell ELISpot assay and Abs by conventional serology (ELISA). Results: While DBPII naturally acquired Abs were short-lived and could not be detected 12-yearsafter a single exposure, we found evidences that specific P. vivax MBCs are long-life cells. A significant proportion of exposed individuals (62%) produced antigen-specific MBCS to DBPII variants BR-1. Conclusion: in the absence of re-exposure to parasites, DBPII specific MBCs are maintained for at least 12 years, and longer than the cognate serum Abs. These results are highly encouraging for vaccine developers, since reinforce the hypothesis that vaccine based on DBPIIshould induce long-lasting protection against vivax malaria.