Leveraging Non-Human Primates to Investigate Malaria Infection and Immunity 4437

Abstract Description Malaria remains a significant global health issue, impacting more than half of the world’s population. Although two partially effective vaccines exist, their efficacy declines over time, emphasizing the need for improved vaccines with a T cell component. To achieve this, a better understanding of the immune responses in sites of infection such as the liver, spleen, and lymph nodes, areas is essential. Studying these immunological processes in humans is challenging. Thus, a non-human primate (NHP) model using Plasmodium knowlesi offers valuable insights due to its similarities with humans. This model enabled us to investigate immune cell interactions and transcriptomic changes longitudinally (through biopsies) in the context of vaccine immunity, infection and parasite control in both scenarios. In this study, NHPs were assigned to three cohorts: Group 1 (n = 8) vaccinated with a live attenuated vaccine following infection and challenged; Group 2 (n = 8) vaccinated and challenged; and Group 3 (n = 3) unvaccinated infectivity controls. Biopsied samples underwent single-cell RNA sequencing. NK cells in the liver from Group 2 showed transcriptional activation correlated with protection, along with cytotoxic CD8 T cells aiding in controlling parasitemia. While the specific mechanisms remain unknown, findings indicate a potential synergy between innate and adaptive liver responses. Ongoing analysis of Group 3 aims to identify how the parasite alters immune development during infection. Funding Sources Supported by NIH U01AI165457 Topic Categories Computational and Systems Immunology (COMP)