T cell reactivity to the SARS-CoV-2 Omicron variant is preserved in most but not all individuals

Vivek Naranbhai; Anusha Nathan; Clarety Kaseke; Cristhian Berrios; Ashok Khatri; Shawn Choi; Matthew A. Getz; Rhoda Tano-Menka; Onosereme Ofoman; Alton Gayton; Fernando Senjobe; Zezhou Zhao; Kerri J. St Denis; Evan C. Lam; Mary Carrington; Wilfredo F. Garcia-Beltran; Alejandro B. Balazs; Bruce D. Walker; A. John Iafrate; Gaurav D. Gaiha

doi:10.1016/j.cell.2022.01.029

T cell reactivity to the SARS-CoV-2 Omicron variant is preserved in most but not all individuals

Vivek Naranbhai, Anusha Nathan, Clarety Kaseke, Cristhian Berrios, Ashok Khatri, Shawn Choi, Matthew A. Getz, Rhoda Tano-Menka, Onosereme Ofoman, Alton Gayton, Fernando Senjobe, Zezhou Zhao, Kerri J. St Denis, Evan C. Lam, Mary Carrington, Wilfredo F. Garcia-Beltran, Alejandro B. Balazs, Bruce D. Walker, A. John Iafrate, Gaurav D. Gaiha

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

213 Citations (Scopus)

Abstract

The SARS-CoV-2 Omicron variant (B.1.1.529) contains mutations that mediate escape from antibody responses, although the extent to which these substitutions in spike and non-spike proteins affect T cell recognition is unknown. In this study, we show that T cell responses in individuals with prior infection, vaccination, both prior infection and vaccination, and boosted vaccination are largely preserved to Omicron spike and non-spike proteins. However, we also identify a subset of individuals (∼21%) with a >50% reduction in T cell reactivity to the Omicron spike. Evaluation of functional CD4⁺ and CD8⁺ memory T cell responses confirmed these findings and revealed that reduced recognition to Omicron spike is primarily observed within the CD8⁺ T cell compartment potentially due to escape from HLA binding. Booster vaccination enhanced T cell responses to Omicron spike. In contrast to neutralizing immunity, these findings suggest preservation of T cell responses to the Omicron variant, although with reduced reactivity in some individuals.

Original language	English
Pages (from-to)	1041-1051.e6
Number of pages	18
Journal	Cell
Volume	185
Issue number	6
DOIs	https://doi.org/10.1016/j.cell.2022.01.029
Publication status	Published - 17 Mar 2022
Externally published	Yes

UN SDGs

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

SDG 3 Good Health and Well-being

Keywords

COVID-19
Delta
epitopes
HLA
neutralization
Omicron
SARS-CoV-2
T cell
vaccination
variants

Access to Document

10.1016/j.cell.2022.01.029Licence: CC BY

Cite this

Naranbhai, V., Nathan, A., Kaseke, C., Berrios, C., Khatri, A., Choi, S., Getz, M. A., Tano-Menka, R., Ofoman, O., Gayton, A., Senjobe, F., Zhao, Z., St Denis, K. J., Lam, E. C., Carrington, M., Garcia-Beltran, W. F., Balazs, A. B., Walker, B. D., Iafrate, A. J., & Gaiha, G. D. (2022). T cell reactivity to the SARS-CoV-2 Omicron variant is preserved in most but not all individuals. Cell, 185(6), 1041-1051.e6. https://doi.org/10.1016/j.cell.2022.01.029

@article{6f6d491dc8f448d88d070a211a537c69,

title = "T cell reactivity to the SARS-CoV-2 Omicron variant is preserved in most but not all individuals",

abstract = "The SARS-CoV-2 Omicron variant (B.1.1.529) contains mutations that mediate escape from antibody responses, although the extent to which these substitutions in spike and non-spike proteins affect T cell recognition is unknown. In this study, we show that T cell responses in individuals with prior infection, vaccination, both prior infection and vaccination, and boosted vaccination are largely preserved to Omicron spike and non-spike proteins. However, we also identify a subset of individuals (∼21\%) with a >50\% reduction in T cell reactivity to the Omicron spike. Evaluation of functional CD4+ and CD8+ memory T cell responses confirmed these findings and revealed that reduced recognition to Omicron spike is primarily observed within the CD8+ T cell compartment potentially due to escape from HLA binding. Booster vaccination enhanced T cell responses to Omicron spike. In contrast to neutralizing immunity, these findings suggest preservation of T cell responses to the Omicron variant, although with reduced reactivity in some individuals.",

keywords = "COVID-19, Delta, epitopes, HLA, neutralization, Omicron, SARS-CoV-2, T cell, vaccination, variants",

author = "Vivek Naranbhai and Anusha Nathan and Clarety Kaseke and Cristhian Berrios and Ashok Khatri and Shawn Choi and Getz, \{Matthew A.\} and Rhoda Tano-Menka and Onosereme Ofoman and Alton Gayton and Fernando Senjobe and Zezhou Zhao and \{St Denis\}, \{Kerri J.\} and Lam, \{Evan C.\} and Mary Carrington and Garcia-Beltran, \{Wilfredo F.\} and Balazs, \{Alejandro B.\} and Walker, \{Bruce D.\} and Iafrate, \{A. John\} and Gaiha, \{Gaurav D.\}",

note = "Funding Information: We thank Shiv Pillai, MD PhD for excellent advice on this manuscript. We thank Anand Dighe, MD; Andrea Nixon, BS; and the MGH Core Laboratory for assistance with clinical SARS-CoV-2 serology testing. This work was supported by the Peter and Ann Lambertus Family Foundation . This study was supported by NIH grants P01 DK011794-51A1 (A.K.), R01AI149704 (B.D.W.), UM1AI144462 (G.D.G. and B.D.W.), and DP2AI154421 (G.D.G.) and a grant from the Massachusetts Consortium on Pathogenesis Readiness (MassCPR) (G.D.G.). Additional support was provided by the Howard Hughes Medical Institute (B.D.W.), the Ragon Institute of MGH, MIT and Harvard (B.D.W. and G.D.G.), the Mark and Lisa Schwartz Foundation and Enid Schwartz (B.D.W.), and Sandy and Paul Edgerly. V.N. received support from a Medscape Young Investigators Lung Cancer award. A.B.B. was supported by the National Institutes for Drug Abuse (NIDA) Avenir New Innovator award DP2DA040254 , the MGH Transformative Scholars Program , and a Massachusetts Consortium on Pathogenesis Readiness (MassCPR) grant. G.D.G. is supported by the Bill and Melinda Gates Foundation , a Burroughs Wellcome Career Award for Medical Scientists, and the Gilead HIV Research Scholars Program . This project has been funded in whole or in part with federal funds from the Frederick National Laboratory for Cancer Research under contract no. HHSN261200800001E . The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. This Research was supported in part by the Intramural Research Program of the NIH , Frederick National Lab , and Center for Cancer Research . Funding Information: We thank Shiv Pillai, MD PhD for excellent advice on this manuscript. We thank Anand Dighe, MD; Andrea Nixon, BS; and the MGH Core Laboratory for assistance with clinical SARS-CoV-2 serology testing. This work was supported by the Peter and Ann Lambertus Family Foundation. This study was supported by NIH grants P01 DK011794-51A1 (A.K.), R01AI149704 (B.D.W.), UM1AI144462 (G.D.G. and B.D.W.), and DP2AI154421 (G.D.G.) and a grant from the Massachusetts Consortium on Pathogenesis Readiness (MassCPR) (G.D.G.). Additional support was provided by the Howard Hughes Medical Institute (B.D.W.), the Ragon Institute of MGH, MIT and Harvard (B.D.W. and G.D.G.), the Mark and Lisa Schwartz Foundation and Enid Schwartz (B.D.W.), and Sandy and Paul Edgerly. V.N. received support from a Medscape Young Investigators Lung Cancer award. A.B.B. was supported by the National Institutes for Drug Abuse (NIDA) Avenir New Innovator award DP2DA040254, the MGH Transformative Scholars Program, and a Massachusetts Consortium on Pathogenesis Readiness (MassCPR) grant. G.D.G. is supported by the Bill and Melinda Gates Foundation, a Burroughs Wellcome Career Award for Medical Scientists, and the Gilead HIV Research Scholars Program. This project has been funded in whole or in part with federal funds from the Frederick National Laboratory for Cancer Research under contract no. HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. This Research was supported in part by the Intramural Research Program of the NIH, Frederick National Lab, and Center for Cancer Research. Conceptualization, V.N. B.D.W. A.J.I. and G.D.G.; formal analysis, V.N. A.N. and G.D.G.; methodology and investigation, V.N. A.N. C.K. C.B. M.A.G. R.T.-M. O.O. A.G. F.S. Z.Z. K.J.S.D. E.C.L. M.C. W.F.G.-B. A.B.B. and G.D.G.; resources, A.K. and S.C.; writing ? original draft, V.N. A.N. and G.D.G.; funding acquisition, A.B.B. B.D.W. A.J.I. and G.D.G.; supervision, A.B.B. A.J.I. and G.D.G. G.D.G. has filed patent application PCT/US2021/028245. We worked to ensure gender balance in the recruitment of human subjects. We worked to ensure ethnic or other types of diversity in the recruitment of human subjects. We worked to ensure that the study questionnaires were prepared in an inclusive way. One or more of the authors of this paper self-identifies as an underrepresented ethnic minority in science. One or more of the authors of this paper self-identifies as a member of the LGBTQ+ community. Publisher Copyright: {\textcopyright} 2022 The Author(s)",

year = "2022",

month = mar,

day = "17",

doi = "10.1016/j.cell.2022.01.029",

language = "English",

volume = "185",

pages = "1041--1051.e6",

journal = "Cell",

issn = "0092-8674",

publisher = "Cell Press",

number = "6",

}

Naranbhai, V, Nathan, A, Kaseke, C, Berrios, C, Khatri, A, Choi, S, Getz, MA, Tano-Menka, R, Ofoman, O, Gayton, A, Senjobe, F, Zhao, Z, St Denis, KJ, Lam, EC, Carrington, M, Garcia-Beltran, WF, Balazs, AB, Walker, BD, Iafrate, AJ & Gaiha, GD 2022, 'T cell reactivity to the SARS-CoV-2 Omicron variant is preserved in most but not all individuals', Cell, vol. 185, no. 6, pp. 1041-1051.e6. https://doi.org/10.1016/j.cell.2022.01.029

TY - JOUR

T1 - T cell reactivity to the SARS-CoV-2 Omicron variant is preserved in most but not all individuals

AU - Naranbhai, Vivek

AU - Nathan, Anusha

AU - Kaseke, Clarety

AU - Berrios, Cristhian

AU - Khatri, Ashok

AU - Choi, Shawn

AU - Getz, Matthew A.

AU - Tano-Menka, Rhoda

AU - Ofoman, Onosereme

AU - Gayton, Alton

AU - Senjobe, Fernando

AU - Zhao, Zezhou

AU - St Denis, Kerri J.

AU - Lam, Evan C.

AU - Carrington, Mary

AU - Garcia-Beltran, Wilfredo F.

AU - Balazs, Alejandro B.

AU - Walker, Bruce D.

AU - Iafrate, A. John

AU - Gaiha, Gaurav D.

N1 - Funding Information: We thank Shiv Pillai, MD PhD for excellent advice on this manuscript. We thank Anand Dighe, MD; Andrea Nixon, BS; and the MGH Core Laboratory for assistance with clinical SARS-CoV-2 serology testing. This work was supported by the Peter and Ann Lambertus Family Foundation . This study was supported by NIH grants P01 DK011794-51A1 (A.K.), R01AI149704 (B.D.W.), UM1AI144462 (G.D.G. and B.D.W.), and DP2AI154421 (G.D.G.) and a grant from the Massachusetts Consortium on Pathogenesis Readiness (MassCPR) (G.D.G.). Additional support was provided by the Howard Hughes Medical Institute (B.D.W.), the Ragon Institute of MGH, MIT and Harvard (B.D.W. and G.D.G.), the Mark and Lisa Schwartz Foundation and Enid Schwartz (B.D.W.), and Sandy and Paul Edgerly. V.N. received support from a Medscape Young Investigators Lung Cancer award. A.B.B. was supported by the National Institutes for Drug Abuse (NIDA) Avenir New Innovator award DP2DA040254 , the MGH Transformative Scholars Program , and a Massachusetts Consortium on Pathogenesis Readiness (MassCPR) grant. G.D.G. is supported by the Bill and Melinda Gates Foundation , a Burroughs Wellcome Career Award for Medical Scientists, and the Gilead HIV Research Scholars Program . This project has been funded in whole or in part with federal funds from the Frederick National Laboratory for Cancer Research under contract no. HHSN261200800001E . The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. This Research was supported in part by the Intramural Research Program of the NIH , Frederick National Lab , and Center for Cancer Research . Funding Information: We thank Shiv Pillai, MD PhD for excellent advice on this manuscript. We thank Anand Dighe, MD; Andrea Nixon, BS; and the MGH Core Laboratory for assistance with clinical SARS-CoV-2 serology testing. This work was supported by the Peter and Ann Lambertus Family Foundation. This study was supported by NIH grants P01 DK011794-51A1 (A.K.), R01AI149704 (B.D.W.), UM1AI144462 (G.D.G. and B.D.W.), and DP2AI154421 (G.D.G.) and a grant from the Massachusetts Consortium on Pathogenesis Readiness (MassCPR) (G.D.G.). Additional support was provided by the Howard Hughes Medical Institute (B.D.W.), the Ragon Institute of MGH, MIT and Harvard (B.D.W. and G.D.G.), the Mark and Lisa Schwartz Foundation and Enid Schwartz (B.D.W.), and Sandy and Paul Edgerly. V.N. received support from a Medscape Young Investigators Lung Cancer award. A.B.B. was supported by the National Institutes for Drug Abuse (NIDA) Avenir New Innovator award DP2DA040254, the MGH Transformative Scholars Program, and a Massachusetts Consortium on Pathogenesis Readiness (MassCPR) grant. G.D.G. is supported by the Bill and Melinda Gates Foundation, a Burroughs Wellcome Career Award for Medical Scientists, and the Gilead HIV Research Scholars Program. This project has been funded in whole or in part with federal funds from the Frederick National Laboratory for Cancer Research under contract no. HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. This Research was supported in part by the Intramural Research Program of the NIH, Frederick National Lab, and Center for Cancer Research. Conceptualization, V.N. B.D.W. A.J.I. and G.D.G.; formal analysis, V.N. A.N. and G.D.G.; methodology and investigation, V.N. A.N. C.K. C.B. M.A.G. R.T.-M. O.O. A.G. F.S. Z.Z. K.J.S.D. E.C.L. M.C. W.F.G.-B. A.B.B. and G.D.G.; resources, A.K. and S.C.; writing ? original draft, V.N. A.N. and G.D.G.; funding acquisition, A.B.B. B.D.W. A.J.I. and G.D.G.; supervision, A.B.B. A.J.I. and G.D.G. G.D.G. has filed patent application PCT/US2021/028245. We worked to ensure gender balance in the recruitment of human subjects. We worked to ensure ethnic or other types of diversity in the recruitment of human subjects. We worked to ensure that the study questionnaires were prepared in an inclusive way. One or more of the authors of this paper self-identifies as an underrepresented ethnic minority in science. One or more of the authors of this paper self-identifies as a member of the LGBTQ+ community. Publisher Copyright: © 2022 The Author(s)

PY - 2022/3/17

Y1 - 2022/3/17

N2 - The SARS-CoV-2 Omicron variant (B.1.1.529) contains mutations that mediate escape from antibody responses, although the extent to which these substitutions in spike and non-spike proteins affect T cell recognition is unknown. In this study, we show that T cell responses in individuals with prior infection, vaccination, both prior infection and vaccination, and boosted vaccination are largely preserved to Omicron spike and non-spike proteins. However, we also identify a subset of individuals (∼21%) with a >50% reduction in T cell reactivity to the Omicron spike. Evaluation of functional CD4+ and CD8+ memory T cell responses confirmed these findings and revealed that reduced recognition to Omicron spike is primarily observed within the CD8+ T cell compartment potentially due to escape from HLA binding. Booster vaccination enhanced T cell responses to Omicron spike. In contrast to neutralizing immunity, these findings suggest preservation of T cell responses to the Omicron variant, although with reduced reactivity in some individuals.

AB - The SARS-CoV-2 Omicron variant (B.1.1.529) contains mutations that mediate escape from antibody responses, although the extent to which these substitutions in spike and non-spike proteins affect T cell recognition is unknown. In this study, we show that T cell responses in individuals with prior infection, vaccination, both prior infection and vaccination, and boosted vaccination are largely preserved to Omicron spike and non-spike proteins. However, we also identify a subset of individuals (∼21%) with a >50% reduction in T cell reactivity to the Omicron spike. Evaluation of functional CD4+ and CD8+ memory T cell responses confirmed these findings and revealed that reduced recognition to Omicron spike is primarily observed within the CD8+ T cell compartment potentially due to escape from HLA binding. Booster vaccination enhanced T cell responses to Omicron spike. In contrast to neutralizing immunity, these findings suggest preservation of T cell responses to the Omicron variant, although with reduced reactivity in some individuals.

KW - COVID-19

KW - Delta

KW - epitopes

KW - HLA

KW - neutralization

KW - Omicron

KW - SARS-CoV-2

KW - T cell

KW - vaccination

KW - variants

UR - https://www.scopus.com/pages/publications/85125465144

U2 - 10.1016/j.cell.2022.01.029

DO - 10.1016/j.cell.2022.01.029

M3 - Article

C2 - 35202566

AN - SCOPUS:85125465144

SN - 0092-8674

VL - 185

SP - 1041-1051.e6

JO - Cell

JF - Cell

IS - 6

ER -

T cell reactivity to the SARS-CoV-2 Omicron variant is preserved in most but not all individuals

Abstract

UN SDGs

Keywords

Access to Document

Other files and links

Erratum: T cell reactivity to the SARS-CoV-2 Omicron variant is preserved in most but not all individuals (Cell (2022) 185(6) (1041–1051.e6), (S0092867422001404), (10.1016/j.cell.2022.01.029))

Cite this