Evidence of premature lymphocyte aging in people with low anti-spike antibody levels after BNT162b2 vaccination

Yapei Huang; Juliana E Shin; Alexander M Xu; Changfu Yao; Sandy Joung; Min Wu; Ruan Zhang; Bongha Shin; Joslyn Foley; Simeon B Mahov; Matthew E Modes; Joseph E Ebinger; Matthew Driver; Jonathan G Braun; Caroline A Jefferies; Tanyalak Parimon; Chelsea Hayes; Kimia Sobhani; Akil Merchant; Sina A Gharib; Stanley C Jordan; Susan Cheng; Helen S Goodridge; Peter Chen

doi:10.1016/j.isci.2022.105209

Evidence of premature lymphocyte aging in people with low anti-spike antibody levels after BNT162b2 vaccination

iScience. 2022 Oct 21;25(10):105209. doi: 10.1016/j.isci.2022.105209. Epub 2022 Sep 26.

Authors

Yapei Huang¹, Juliana E Shin^{2

3}, Alexander M Xu^{2

4}, Changfu Yao^{1

2}, Sandy Joung⁵, Min Wu⁵, Ruan Zhang⁶, Bongha Shin⁶, Joslyn Foley^{2

4}, Simeon B Mahov^{2

4}, Matthew E Modes¹, Joseph E Ebinger⁵, Matthew Driver⁵, Jonathan G Braun^{3

7

8}, Caroline A Jefferies^{3

9}, Tanyalak Parimon¹, Chelsea Hayes⁸, Kimia Sobhani⁸, Akil Merchant^{2

4}, Sina A Gharib¹⁰, Stanley C Jordan⁶, Susan Cheng⁵, Helen S Goodridge^{2

3}, Peter Chen¹

Affiliations

¹ Women's Guild Lung Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
² Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
³ Research Division of Immunology in the Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
⁴ Division of Hematology and Cellular Therapy, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
⁵ Department of Cardiology, Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
⁶ Comprehensive Transplant Center, Transplant Immunology Laboratory, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
⁷ F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
⁸ Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
⁹ Department of Medicine, Division of Rheumatology, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
¹⁰ Computational Medicine Core at Center for Lung Biology, Division of Pulmonary, Critical Care and Sleep Medicine, University of Washington, Seattle, WA 98109, USA.

Abstract

SARS-CoV-2 vaccines have unquestionably blunted the overall impact of the COVID-19 pandemic, but host factors such as age, sex, obesity, and other co-morbidities can affect vaccine efficacy. We identified individuals in a relatively healthy population of healthcare workers (CORALE study cohort) who had unexpectedly low peak anti-spike receptor binding domain (S-RBD) antibody levels after receiving the BNT162b2 vaccine. Compared to matched controls, "low responders" had fewer spike-specific antibody-producing B cells after the second and third/booster doses. Moreover, their spike-specific T cell receptor (TCR) repertoire had less depth and their CD4⁺ and CD8⁺T cell responses to spike peptide stimulation were less robust. Single cell transcriptomic evaluation of peripheral blood mononuclear cells revealed activation of aging pathways in low responder B and CD4⁺T cells that could underlie their attenuated anti-S-RBD antibody production. Premature lymphocyte aging may therefore contribute to a less effective humoral response and could reduce vaccination efficacy.

Keywords: Health sciences; Immunology; Microbiology; Transcriptomics.

Abstract

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