iScience (Oct 2022)
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
Affiliations
- Yapei Huang
- Women’s Guild Lung Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
- Juliana E. Shin
- Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Research Division of Immunology in the Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
- Alexander M. Xu
- Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Division of Hematology and Cellular Therapy, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
- Changfu Yao
- Women’s Guild Lung Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
- Sandy Joung
- Department of Cardiology, Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
- Min Wu
- Department of Cardiology, Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
- Ruan Zhang
- Comprehensive Transplant Center, Transplant Immunology Laboratory, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
- Bongha Shin
- Comprehensive Transplant Center, Transplant Immunology Laboratory, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
- Joslyn Foley
- Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Division of Hematology and Cellular Therapy, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
- Simeon B. Mahov
- Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Division of Hematology and Cellular Therapy, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
- Matthew E. Modes
- Women’s Guild Lung Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
- Joseph E. Ebinger
- Department of Cardiology, Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
- Matthew Driver
- Department of Cardiology, Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
- Jonathan G. Braun
- Research Division of Immunology in the Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
- Caroline A. Jefferies
- Research Division of Immunology in the Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Department of Medicine, Division of Rheumatology, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
- Tanyalak Parimon
- Women’s Guild Lung Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
- Chelsea Hayes
- Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
- Kimia Sobhani
- Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
- Akil Merchant
- Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Division of Hematology and Cellular Therapy, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
- Sina A. Gharib
- Computational Medicine Core at Center for Lung Biology, Division of Pulmonary, Critical Care and Sleep Medicine, University of Washington, Seattle, WA 98109, USA
- Stanley C. Jordan
- Comprehensive Transplant Center, Transplant Immunology Laboratory, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
- Susan Cheng
- Department of Cardiology, Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Corresponding author
- Helen S. Goodridge
- Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Research Division of Immunology in the Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Corresponding author
- Peter Chen
- Women’s Guild Lung Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Corresponding author
- Journal volume & issue
-
Vol. 25,
no. 10
p. 105209
Abstract
Summary: 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.
