A Review of Immune Responses to Plasmodium vivax Duffy Binding Protein from a 15-Year Follow-up Study in an Area of Unstable Malaria Transmission in the Amazon

Abstract Plasmodium vivax , the second most common human malaria parasite, remains a major public health concern, and no vaccine has yet been approved. Nevertheless, a recent clinical trial provided evidence of partial protection by a vaccine targeting Duffy binding protein region II (DBPII), a ligand that mediates reticulocyte invasion through its interaction with the human atypical chemokine receptor 1 (ACKR1), also known as the Duffy antigen receptor for chemokines (DARC). This success supports the DBPII/DARC interaction as a validated and promising target for blood-stage vaccines against P. vivax . Amid progress in the development of P. vivax blood-stage vaccines, we are investigating immune responses to DBPII in individuals exposed to different levels of malaria transmission in Brazil. Here, we reviewed key advances in DBP research and analyzed data from a 15-year open cohort of P. vivax -exposed individuals in the Brazilian Amazon, providing new insights into immune features associated with persistent DBPII antibody responses and protection against malaria.