@article{23aa717f1bb743dd9f4360f155136c22,
title = "SARS-CoV-2 breakthrough infection induces rapid memory and de novo T cell responses",
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.",
keywords = "breakthrough infection, CD4 T cell immunity, CD8 T cell immunity, COVID-19 vaccines, Delta, multimer, Omicron, SARS-CoV-2, T cell, vaccination",
author = "Marios Koutsakos and Arnold Reynaldi and Lee, {Wen Shi} and Julie Nguyen and Thakshila Amarasena and George Taiaroa and Paul Kinsella and Liew, {Kwee Chin} and Thomas Tran and Kent, {Helen E.} and Tan, {Hyon Xhi} and Rowntree, {Louise C.} and Nguyen, {Thi H.O.} and Thomas, {Paul G.} and Katherine Kedzierska and Jan Petersen and Jamie Rossjohn and Williamson, {Deborah A.} and David Khoury and Davenport, {Miles P.} and Kent, {Stephen J.} and Wheatley, {Adam K.} and Juno, {Jennifer A.}",
note = "Funding Information: We thank the participants for their generous involvement and provision of samples. We thank the molecular staff at the Victorian Infectious Diseases Reference Laboratory for performing real-time PCR and Ms. Grace Gare for technical assistance. We thank Dr. Julian Druce and Dr. Leon Caly at the Victorian Infectious Diseases Reference Laboratory for isolating and distributing SARS-CoV-2 virus isolates. We thank A/Prof Stuart Turville from the Kirby Institute, University of New South Wales for technical expertise and sharing the HAT-24 cell line. We acknowledge the Melbourne Cytometry Platform for provision of flow cytometry services. The graphical abstract was created with BioRender. The work has been generously supported by the Morningside Foundation and by the Australian National Health and Medical Research Council grants 1149990 , 1162760 , 1194036, and 2004398 ; Australian Medical Research Future Fund grants 2005544 , 2016062, and 2013870 ; The Victorian Government ; and Australian National Health and Medical Research Council Investigator or Fellowship grants (M.K., A.K.W., J.A.J., H.-X.T., D.A.W., M.P.D., K.K., T.H.O.N., and S.J.K.). Publisher Copyright: {\textcopyright} 2023 Elsevier Inc.",
year = "2023",
month = apr,
day = "11",
doi = "10.1016/j.immuni.2023.02.017",
language = "English",
volume = "56",
pages = "879--892.e4",
journal = "Immunity",
issn = "1074-7613",
publisher = "Elsevier",
number = "4",
}
