SARS-CoV-2 breakthrough infection induces rapid memory and de novo T cell responses

Koutsakos, Marios, Reynaldi, Arnold, Lee, Wen Shi, Nguyen, Julie, Amarasena, Thakshila, Taiaroa, George, Kinsella, Paul, Liew, Kwee Chin, Tran, Thomas, Kent, Helen E., Tan, Hyon-Xhi, Rowntree, Louise C., Nguyen, Thi H.O., Thomas, Paul G., Kedzierska, Katherine, Petersen, Jan, Rossjohn, Jamie ORCID: https://orcid.org/0000-0002-2020-7522, Williamson, Deborah A., Khoury, David, Davenport, Miles P., Kent, Stephen J., Wheatley, Adam K. and Juno, Jennifer A. 2023. SARS-CoV-2 breakthrough infection induces rapid memory and de novo T cell responses. Immunity 56 (4) , pp. 879-892. 10.1016/j.immuni.2023.02.017

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Abstract

Although the protective role of neutralizing antibodies against COVID-19 is well established, questions remain about the relative importance of cellular immunity. Using 6 pMHC multimers in a cohort with early and frequent sampling, we define the phenotype and kinetics of recalled and primary T cell responses following Delta or Omicron breakthrough infection in previously vaccinated individuals. Recall of spike-specific CD4+ T cells was rapid, with cellular proliferation and extensive activation evident as early as 1 day post symptom onset. Similarly, spike-specific CD8+ T cells were rapidly activated but showed variable degrees of expansion. The frequency of activated SARS-CoV-2-specific CD8+ T cells at baseline and peak inversely correlated with peak SARS-CoV-2 RNA levels in nasal swabs and accelerated viral clearance. Our study demonstrates that a rapid and extensive recall of memory T cell populations occurs early after breakthrough infection and suggests that CD8+ T cells contribute to the control of viral replication in breakthrough SARS-CoV-2 infections

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Publisher:	Elsevier
ISSN:	1074-7613
Date of Acceptance:	24 February 2023
Last Modified:	03 May 2023 13:09
URI:	https://orca.cardiff.ac.uk/id/eprint/158489

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