Pre-existing immunity levels are essential for expanding long-lived influenza-specific memory CD8 T-cells following vaccination 2634

Abstract Description Understanding the dynamics of human memory CD8 T cells in influenza immunity remains challenging. We investigated how pre-existing immunity influences memory T cell formation by administering the live attenuated influenza vaccine (LAIV) to children with varying LAIV exposure histories. Utilizing high-dimensional mass cytometry, transcriptomic, and plasma protein analyses, we characterized influenza-specific T cells and identified host factors driving their establishment. Our primary finding demonstrates that sufficient pre-existing influenza immunity—established through repeated LAIV vaccinations—is necessary to significantly expand influenza-specific memory CD8 T cells, particularly stem-cell-like memory T cells (TSCM) with long-lasting protective capabilities. Enhanced TSCM responses correlated with a robust innate antiviral genetic signature, including heightened interferon signaling pathways and increased serum levels of pro-inflammatory cytokines, indicative of an effective antiviral response. These results highlight that repeated influenza exposures help achieve the necessary pre-existing immunity levels to foster durable influenza-specific memory CD8 T-cell populations, strengthening the body’s defense against influenza. Our findings advocate for vaccination strategies that effectively consider individual pre-existing immunity levels to prime the immune system for future influenza challenges. Topic Categories Vaccines and Immunotherapy (VAC)