Spheromers reveal robust T cell responses to the Pfizer/BioNTech vaccine and attenuated peripheral CD8+ T cell responses post SARS-CoV-2 infection

Fei Gao; Vamsee Mallajosyula; Prabhu S Arunachalam; Kattria van der Ploeg; Monali Manohar; Katharina Röltgen; Fan Yang; Oliver Wirz; Ramona Hoh; Emily Haraguchi; Ji-Yeun Lee; Richard Willis; Vasanthi Ramachandiran; Jiefu Li; Karan Raj Kathuria; Chunfeng Li; Alexandra S Lee; Mihir M Shah; Sayantani B Sindher; Joseph Gonzalez; John D Altman; Taia T Wang; Scott D Boyd; Bali Pulendran; Prasanna Jagannathan; Kari C Nadeau; Mark M Davis

doi:10.1016/j.immuni.2023.03.005

Spheromers reveal robust T cell responses to the Pfizer/BioNTech vaccine and attenuated peripheral CD8⁺ T cell responses post SARS-CoV-2 infection

Immunity. 2023 Apr 11;56(4):864-878.e4. doi: 10.1016/j.immuni.2023.03.005. Epub 2023 Mar 16.

Authors

Fei Gao¹, Vamsee Mallajosyula¹, Prabhu S Arunachalam¹, Kattria van der Ploeg², Monali Manohar³, Katharina Röltgen⁴, Fan Yang⁴, Oliver Wirz⁴, Ramona Hoh⁴, Emily Haraguchi⁴, Ji-Yeun Lee⁴, Richard Willis⁵, Vasanthi Ramachandiran⁵, Jiefu Li¹, Karan Raj Kathuria¹, Chunfeng Li¹, Alexandra S Lee³, Mihir M Shah³, Sayantani B Sindher³, Joseph Gonzalez⁶, John D Altman⁷, Taia T Wang⁸, Scott D Boyd⁹, Bali Pulendran¹⁰, Prasanna Jagannathan⁸, Kari C Nadeau¹¹, Mark M Davis¹²

Affiliations

¹ Institute for Immunity, Transplantation, and Infection, Stanford University School of Medicine, Stanford, CA, USA.
² Department of Medicine, Division of Infectious Diseases, Stanford University, Stanford, CA, USA.
³ Sean N. Parker Center for Allergy and Asthma Research, Stanford University and Division of Pulmonary, Allergy, and Critical Care Medicine, Stanford University School of Medicine, Stanford, CA, USA.
⁴ Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
⁵ Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA, USA.
⁶ Department of Microbiology and Immunology, Stanford University, Stanford, CA, USA.
⁷ Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA, USA; Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA, USA.
⁸ Department of Medicine, Division of Infectious Diseases, Stanford University, Stanford, CA, USA; Department of Microbiology and Immunology, Stanford University, Stanford, CA, USA.
⁹ Sean N. Parker Center for Allergy and Asthma Research, Stanford University and Division of Pulmonary, Allergy, and Critical Care Medicine, Stanford University School of Medicine, Stanford, CA, USA; Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
¹⁰ Institute for Immunity, Transplantation, and Infection, Stanford University School of Medicine, Stanford, CA, USA; Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA; Department of Microbiology and Immunology, Stanford University, Stanford, CA, USA.
¹¹ Institute for Immunity, Transplantation, and Infection, Stanford University School of Medicine, Stanford, CA, USA; Sean N. Parker Center for Allergy and Asthma Research, Stanford University and Division of Pulmonary, Allergy, and Critical Care Medicine, Stanford University School of Medicine, Stanford, CA, USA; Department of Environmental Health, Harvard T.H. Chan School of Public Health, Harvard, MA, USA.
¹² Institute for Immunity, Transplantation, and Infection, Stanford University School of Medicine, Stanford, CA, USA; Department of Microbiology and Immunology, Stanford University, Stanford, CA, USA; Howard Hughes Medical Institute, Stanford University, Stanford, CA, USA. Electronic address: mmdavis@stanford.edu.

Abstract

T cells are a critical component of the response to SARS-CoV-2, but their kinetics after infection and vaccination are insufficiently understood. Using "spheromer" peptide-MHC multimer reagents, we analyzed healthy subjects receiving two doses of the Pfizer/BioNTech BNT162b2 vaccine. Vaccination resulted in robust spike-specific T cell responses for the dominant CD4⁺ (HLA-DRB1^∗15:01/S191) and CD8⁺ (HLA-A^∗02/S691) T cell epitopes. Antigen-specific CD4⁺ and CD8⁺ T cell responses were asynchronous, with the peak CD4⁺ T cell responses occurring 1 week post the second vaccination (boost), whereas CD8⁺ T cells peaked 2 weeks later. These peripheral T cell responses were elevated compared with COVID-19 patients. We also found that previous SARS-CoV-2 infection resulted in decreased CD8⁺ T cell activation and expansion, suggesting that previous infection can influence the T cell response to vaccination.

Keywords: COVID-19; Pfizer/BioNTech mRNA vaccine; SARS-CoV-2; SARS-CoV-2 variants of concern; antigen-specific T cell responses; peptide-MHC multimer; peripheral CD4(+) T cell responses; peripheral CD8(+) T cell responses; spheromer.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Antibodies, Viral
BNT162 Vaccine
CD8-Positive T-Lymphocytes
COVID-19*
Humans
SARS-CoV-2
Vaccination
Vaccines*

Substances

BNT162 Vaccine
Vaccines
Antibodies, Viral

Abstract

Publication types

MeSH terms

Substances

Grants and funding