IL-15 enhances T resident memory formation and function following genetically attenuated Plasmodium vaccination in mice 3232

Description Tissue resident memory T (Trm) cells are critical for local protection against invading pathogens and are being targeted for vaccination strategies. Malaria is a major public health threat in need of durable vaccines, as it causes 250 million infections annually leading to > 600,000 deaths. Following a mosquito bite, Plasmodium sporozoites (SPZ) travel to the liver and infect hepatocytes. Stopping Plasmodium infection at the liver stage prevents the disease-causing blood stage and transmission to mosquitoes. Vaccine-induced liver Trm cells will be critical for durable protection against malaria. We sought to test IL-15 as an adjuvant since we found that treatment of mice with IL-15 combined with IL-15Rα (IL-15 complex; IL-15C) increases the number of Trm-like CXCR6+ CD8 and CD4 T cells in the liver. Using a Plasmodium yoelii genetically attenuated whole SPZ vaccine that expresses the model antigen ovalbumin (OVA), we found that IL-15C treatment increases the number of polyclonal and OVA-specific CXCR6+CD69+ CD8 Trm cells and the number of polyclonal CXCR6+CD44+ CD4 Trm cells in the liver. IL-15C treatment also increases IFN-γ production by CD8 and CD4 T cells in the liver and increases Plasmodium-specific antibody levels. Furthermore, IL-15C improves vaccine efficacy following challenge with SPZ. Overall, our findings better define liver Trm differentiation, survival, and function and will inform vaccine design against malaria.