Mucosal cellular immunology in SARS CoV2 infection and hybrid immunity 2309658

Abstract Introduction Mucosal immunity is critical in protection against COVID-19 respiratory disease. It is still unclear how the dynamics at the site of infection change between vaccination or natural infection alone and hybrid immunity. Growing evidence supports the importance of T-cell response in circumventing escape variants but we lack an understanding of the magnitude and durability of those responses within different tissues and if they correlate to the protective benefits seen during wanning antibody response Methods We utilized the mouse-adapted SARS CoV2 model, collecting upper and lower respiratory tissues to identify the rise and contraction of T-cell responses following the induction of different immune experiences. One group was exposed intranasally to the virus twice where hybrid groups received intramuscular vaccination that either preceded or followed by intranasal virus. Samples were analyzed with multiparameter flow panels to determine intracellular cytokine response and well as the type of memory subpopulations that arose. Results Distinct patterns were identified of T-cell polyfunctionality and memory population development between groups and across tissue types. Regardless of the order of exposure hybrid immunity mice had greater central, effector and tissue resident memory than repeat infection as well as increased cytokine response. Conclusion Hybrid immunity provided a substantial improvement in the development of SARS CoV2 specific T-cells over repetitive natural infection in systemic and mucosal tissues. Mucosal stimulation and cellular immunity are gaps that should be addressed in future vaccine design. Funding Source UC7 AI180310 Topic Categories Mucosal and Regional Immunology (MUC)