AUTHOR=Florian David M. , Bauer Michael , Popovitsch Amelie , Fae Ingrid , Springer David N. , Graninger Marianne , Traugott Marianna , Weseslindtner Lukas , Aberle Stephan W. , Fischer Gottfried , Kundi Michael , Stiasny Karin , Zoufaly Alexander , Landry Samuel J. , Aberle Judith H. 

TITLE=Enhanced and long-lasting SARS-CoV-2 immune memory in individuals with common cold coronavirus cross-reactive T cell immunity

JOURNAL=Frontiers in Immunology

VOLUME=Volume 16 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1501704

DOI=10.3389/fimmu.2025.1501704

ISSN=1664-3224

ABSTRACT=With the continuous emergence of novel SARS-CoV-2 variants, long-lasting and broadly reactive cellular and humoral immunity is critical for durable protection from COVID-19. We investigated SARS-CoV-2-specific T cell immunity in relation to antibodies, infection outcome and disease severity and assessed its durability in a longitudinal cohort over a three-year time course. We identified pre-existing T cells reactive to the seasonal coronavirus (CoV) OC43 that cross-react with the conserved SARS-CoV-2 spike S813-829 peptide. These cross-reactive T cells increased in frequency following SARS-CoV-2 infection or vaccination and correlated with enhanced spike-specific T cell responses and significantly reduced viral loads. Furthermore, our data revealed that CoV-cross-reactive T cells were maintained as part of the long-lasting memory response, contributing to increased T cell frequencies against omicron variants. These findings suggest a functional role of CoV-cross-reactive T cells that extends beyond the initial SARS-CoV-2 exposure, contributing to enhanced immunity against highly mutated SARS-CoV-2 variants.