Enhancing lung immunity against COVID-19: the role of ATP in TRM cell generation 9389

Abstract Description Vaccination is essential for preventing viral infections and promoting public health; however, its efficacy may vary due to factors such as the nature of the pathogen, vaccine type, and individual immune response. It is known that intranasal immunizations can enhance the immune response by stimulating tissue-resident memory T cells (TRMs), which promote early viral clearance at the infection site. Our study aims to optimize the generation and maintenance of TRMs in the lungs using purinergic signaling components as adjuvants. For this, we crossed B knockout mice with hACE2 mice, generating a B cell-deficient lineage capable of internalizing active SARS-CoV-2 (BKO-hACE2). C57BL/6 and BKO-hACE2 mice were immunized with inactivated SARS-CoV-2 receiving one intravenous dose followed by three intranasal booster doses. After 30 days, lungs were analyzed by flow cytometry and histopathology. Additionally, we evaluated the effects of ATP (0.5 mM to 10 mM) during immunizations, finding that lower doses (0.5 mM) increased the frequency of TRMs (CD4+ and CD8+), while higher doses reduced this population. This suggests that ATP may interact with the P2X7 receptor, promoting either proliferation or cell death. Although infection data did not provide conclusive evidence of T cell-mediated protection in the absence of antibodies, the potential of ATP as a possible adjuvant opens new avenues for enhancing immune responses in experimental models. Funding Sources FAPESP - 2023/15373-9 Topic Categories Viral Immunology (VIR)