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

Marios Koutsakos, Arnold Reynaldi, Wen Shi Lee, Julie Nguyen, Thakshila Amarasena, George Taiaroa, Paul Kinsella, Kwee Chin Liew, Thomas Tran, Helen E. Kent, Hyon Xhi Tan, Louise C. Rowntree, Thi H.O. Nguyen, Paul G. Thomas, Katherine Kedzierska, Jan Petersen, Jamie Rossjohn, Deborah A. Williamson, David Khoury, Miles P. DavenportStephen J. Kent, Adam K. Wheatley, Jennifer A. Juno

Research output: Contribution to journalArticleResearchpeer-review

22 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)879-892.e4
Number of pages18
Issue number4
Publication statusPublished - 11 Apr 2023


  • breakthrough infection
  • CD4 T cell immunity
  • CD8 T cell immunity
  • COVID-19 vaccines
  • Delta
  • multimer
  • Omicron
  • SARS-CoV-2
  • T cell
  • vaccination

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