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 Davenport; Stephen J Kent; Adam K Wheatley; Jennifer A Juno

doi:10.1016/j.immuni.2023.02.017

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^*

^*Corresponding author for this work

School of Medicine

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Pages (from-to)	879-892.e4
Number of pages	18
Journal	Immunity
Volume	56
Issue number	4
Early online date	28 Feb 2023
DOIs	https://doi.org/10.1016/j.immuni.2023.02.017
Publication status	Published - 11 Apr 2023

Keywords

Humans
COVID-19
SARS-CoV-2
CD8-positive T-lymphocytes
Breakthrough infections
RNA, Viral
Antibodies, Neutralizing
Antibodies, Viral
Vaccination

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.immuni.2023.02.017

Cite this

Koutsakos, M., Reynaldi, A., Lee, W. S., Nguyen, J., Amarasena, T., Taiaroa, G., Kinsella, P., Liew, K. C., Tran, T., Kent, H. E., Tan, H.-X., Rowntree, L. C., Nguyen, T. H. O., Thomas, P. G., Kedzierska, K., Petersen, J., Rossjohn, J., Williamson, D. A., Khoury, D., ... Juno, J. A. (2023). SARS-CoV-2 breakthrough infection induces rapid memory and de novo T cell responses. Immunity, 56(4), 879-892.e4. https://doi.org/10.1016/j.immuni.2023.02.017

@article{e5d7d7b1b0424acab05bb66eac2ebb57,

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 = "Humans, COVID-19, SARS-CoV-2, CD8-positive T-lymphocytes, Breakthrough infections, RNA, Viral, Antibodies, Neutralizing, Antibodies, Viral, 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 Hyon-Xhi Tan 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: 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.).",

year = "2023",

month = apr,

day = "11",

doi = "10.1016/j.immuni.2023.02.017",

language = "English",

volume = "56",

pages = "879--892.e4",

journal = "Immunity",

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Koutsakos, M, Reynaldi, A, Lee, WS, Nguyen, J, Amarasena, T, Taiaroa, G, Kinsella, P, Liew, KC, Tran, T, Kent, HE, Tan, H-X, Rowntree, LC, Nguyen, THO, Thomas, PG, Kedzierska, K, Petersen, J, Rossjohn, J, Williamson, DA, Khoury, D, Davenport, MP, Kent, SJ, Wheatley, AK & Juno, JA 2023, 'SARS-CoV-2 breakthrough infection induces rapid memory and de novo T cell responses', Immunity, vol. 56, no. 4, pp. 879-892.e4. https://doi.org/10.1016/j.immuni.2023.02.017

TY - JOUR

T1 - SARS-CoV-2 breakthrough infection induces rapid memory and de novo T cell responses

AU - Koutsakos, Marios

AU - Reynaldi, Arnold

AU - Lee, Wen Shi

AU - Nguyen, Julie

AU - Amarasena, Thakshila

AU - Taiaroa, George

AU - Kinsella, Paul

AU - Liew, Kwee Chin

AU - Tran, Thomas

AU - Kent, Helen E

AU - Tan, Hyon-Xhi

AU - Rowntree, Louise C

AU - Nguyen, Thi H O

AU - Thomas, Paul G

AU - Kedzierska, Katherine

AU - Petersen, Jan

AU - Rossjohn, Jamie

AU - Williamson, Deborah A

AU - Khoury, David

AU - Davenport, Miles P

AU - Kent, Stephen J

AU - Wheatley, Adam K

AU - Juno, Jennifer A

N1 - Funding: 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.).

PY - 2023/4/11

Y1 - 2023/4/11

N2 - 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.

AB - 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.

KW - Humans

KW - COVID-19

KW - SARS-CoV-2

KW - CD8-positive T-lymphocytes

KW - Breakthrough infections

KW - RNA, Viral

KW - Antibodies, Neutralizing

KW - Antibodies, Viral

KW - Vaccination

U2 - 10.1016/j.immuni.2023.02.017

DO - 10.1016/j.immuni.2023.02.017

M3 - Article

C2 - 36958334

SN - 1074-7613

VL - 56

SP - 879-892.e4

JO - Immunity

JF - Immunity

IS - 4