The role of antibody and CD4 follicular helper cells during malaria liver stage infection (P4485)

Abstract The liver stage malaria provides an excellent target for malaria vaccine: eliminating the parasite at this stage using immunization with attenuated parasites that arrest in the liver results in long-term sterile protection. This immune response has been associated with CD8 T cells, as well as antibodiesdirected against the sporozoite. In this study, we hypothesized that genetically attenuated pasite (GAP) immunization induces T follicular helper cells (Tfh), which in turn induce memory B cells responses, leading to long-lived and high avidity functional antibodies to pre-erythrocytic malaria. Using immunization with GAP that arrest during late liver-stage development, we showed that immunization induces high titer antibodies, and that these antibodies can inhibit parasite growth in liver cells in vitro by 99%. To understand the induction of the antibody response, we characterized both the B cell response and the Tfh response in the liver, the spleen and the lymph nodes. Furthermore, in order to determine the localization of the priming of the response, immunization via mosquito bite and intravenous injection were compared. Understanding the role of Tfh in liver stage malaria and how they are induced will be crucial in designing an effective antibody based malaria vaccine.