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

• Published in: iScience Vol. 25; no. 10; p. 105209
• Main Authors: Huang, Yapei, Shin, Juliana E., Xu, Alexander M., Yao, Changfu, Joung, Sandy, Wu, Min, Zhang, Ruan, Shin, Bongha, Foley, Joslyn, Mahov, Simeon B., Modes, Matthew E., Ebinger, Joseph E., Driver, Matthew, Braun, Jonathan G., Jefferies, Caroline A., Parimon, Tanyalak, Hayes, Chelsea, Sobhani, Kimia, Merchant, Akil, Gharib, Sina A., Jordan, Stanley C., Cheng, Susan, Goodridge, Helen S., Chen, Peter
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 21.10.2022; The Author(s); Elsevier
• Subjects: Health sciences; Immunology; Microbiology; Transcriptomics; Health sciences; Immunology; Microbiology; Transcriptomics
• ISSN: 2589-0042; 2589-0042
• DOI: 10.1016/j.isci.2022.105209

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. [Display omitted] •Some relatively healthy individuals mounted weak responses to BNT162b2 vaccination•“Low responders” had impaired spike-specific antibody, B and T cell responses•Transcriptomic analysis revealed evidence of premature lymphocyte aging•Premature lymphocyte aging could reduce vaccination efficacy Health sciences; Immunology; Microbiology; Transcriptomics