Characterizing targets of naturally acquired immunity and correlates of clinical protection against Plasmodium vivax

© 2018 Dr. Wen-Qiang HePlasmodium vivax is the most widely distributed human malaria parasite and accounts for 13 million clinical cases per year. Although it has significant impact on global health systems and can cause severe illness and mortality, only two P. vivax candidate vaccines have reached Phase I clinical trials. Passive transfer of sera from clinically immune individuals significantly protects non-immune recipients from high parasite burden and clinical symptoms. Such observations have established that antibodies are critical for naturally acquired immunity to malaria infection. Therefore, the characterization of antigenic targets of naturally acquired immunity remains a key step towards the identification of novel vaccine candidates. This thesis investigates the breadth of antibody responses to a panel of P. vivax proteins involved in parasite invasion into red blood cells in three longitudinal cohorts from Brazil, Thailand and Papua New Guinea with different transmission intensities. Collectively, the main findings of this thesis have showed several strong associations of antibody responses towards several P. vivax antigens with protection from clinical malaria. Additional protective effects are identified for combinations of P. vivax ligands which supports the inclusion of different P. vivax parasite ligands in a multi-component vaccine