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

Cell. 2022 Mar 17;185(6):1041-1051.e6. doi: 10.1016/j.cell.2022.01.029. Epub 2022 Feb 3.

Authors

Vivek Naranbhai¹, Anusha Nathan², Clarety Kaseke³, Cristhian Berrios⁴, Ashok Khatri⁵, Shawn Choi⁵, Matthew A Getz³, Rhoda Tano-Menka³, Onosereme Ofoman⁴, Alton Gayton³, Fernando Senjobe³, Zezhou Zhao², Kerri J St Denis³, Evan C Lam³, Mary Carrington⁶, Wilfredo F Garcia-Beltran⁷, Alejandro B Balazs³, Bruce D Walker⁸, A John Iafrate⁴, Gaurav D Gaiha⁹

Affiliations

¹ Massachusetts General Hospital Cancer Center, Massachusetts General Hospital, Boston, MA 02114, USA; Dana-Farber Cancer Institute, Boston, MA 02215, USA; Center for the AIDS Programme of Research in South Africa, Durban 4001, South Africa. Electronic address: vnaranbhai@mgh.harvard.edu.
² Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA; Program in Health Sciences & Technology, Harvard Medical School, Massachusetts Institute of Technology, Boston, MA 02115, USA.
³ Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.
⁴ Department of Pathology, Massachusetts General Hospital, Boston, MA 02114, USA.
⁵ Massachusetts General Hospital Endocrine Division and Department of Medicine, Harvard Medical School, Boston, MA 02114, USA.
⁶ Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA; Basic Science Program, Frederick National Laboratory for Cancer Research in the Laboratory of Integrative Cancer Immunology, National Cancer Institute, Bethesda, MD 20892, USA.
⁷ Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA; Department of Pathology, Massachusetts General Hospital, Boston, MA 02114, USA.
⁸ Center for the AIDS Programme of Research in South Africa, Durban 4001, South Africa; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA; The Broad Institute, Cambridge, MA 02142, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA; Institute for Medical Engineering and Science, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
⁹ Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA; Division of Gastroenterology, Massachusetts General Hospital, Boston, MA 02114, USA. Electronic address: ggaiha@mgh.harvard.edu.

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; HLA; Omicron; SARS-CoV-2; T cell; epitopes; neutralization; vaccination; variants.

Abstract

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