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

Authors:

• 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
• Williamson, Deborah A.
• Khoury, David
• Davenport, Miles P.
• Kent, Stephen J.
• Wheatley, Adam K.
• Juno, Jennifer A.

Details:

Immunity, Volume 56, Issue 4, 2023-04-11

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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.