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

tetano

Editor, Senior Moderator
Front Immunol


. 2025 Mar 21:16:1501704.
doi: 10.3389/fimmu.2025.1501704. eCollection 2025. Enhanced and long-lasting SARS-CoV-2 immune memory in individuals with common cold coronavirus cross-reactive T cell immunity

David M Florian[SUP] 1 [/SUP], Michael Bauer[SUP] 1 [/SUP], Amelie Popovitsch[SUP] 1 [/SUP], Ingrid Fae[SUP] 2 [/SUP], David N Springer[SUP] 1 [/SUP], Marianne Graninger[SUP] 1 [/SUP], Marianna Traugott[SUP] 3 [/SUP], Lukas Weseslindtner[SUP] 1 [/SUP], Stephan W Aberle[SUP] 1 [/SUP], Gottfried Fischer[SUP] 2 [/SUP], Michael Kundi[SUP] 4 [/SUP], Karin Stiasny[SUP] 1 [/SUP], Alexander Zoufaly[SUP] 3 5 [/SUP], Samuel J Landry[SUP] 6 [/SUP], Judith H Aberle[SUP] 1 [/SUP]



Affiliations
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 S[SUB]813-829[/SUB] 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.

Keywords: CD4 T cell response; SARS-CoV-2; cell-mediated immunity; long term immunity; mRNA vaccination.

 
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