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

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.

SUBMITTER: Huang Y

PROVIDER: S-EPMC9510055 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature

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

Huang Yapei Y Shin Juliana E JE Xu Alexander M AM Yao Changfu C Joung Sandy S Wu Min M Zhang Ruan R Shin Bongha B Foley Joslyn J Mahov Simeon B SB Modes Matthew E ME Ebinger Joseph E JE Driver Matthew M Braun Jonathan G JG Jefferies Caroline A CA Parimon Tanyalak T Hayes Chelsea C Sobhani Kimia K Merchant Akil A Gharib Sina A SA Jordan Stanley C SC Cheng Susan S Goodridge Helen S HS Chen Peter P

iScience 20220926 10

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 antib ...[more]

PMID: 36188190

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Project description:Simple Summary Upon BNT162b2 mRNA vaccinations, multiple myeloma (MM) and Waldenstrom’s macroglobulinemia (WM) patient cohorts on active therapy affecting B cell development had impaired binding and neutralizing antibody (NAb) response rate and magnitude to wildtype Wuhan (WA1). Patient cohorts on-therapy had significantly lower NAb responses to SARS-CoV-2 Omicron variant BA.4/5 compared to WA1, whereas cohorts off-therapy showed a higher probability to neutralize BA.4/5 after the 3rd vaccination. The boost in NAb after the 3rd dose suggests that repeat vaccination of MM and WM patients is beneficial for several patients even under active therapy. Abstract Patients with symptomatic monoclonal gammopathies have impaired humoral responses to COVID-19 vaccination. Their ability to recognize SARS-CoV-2 Omicron variants is of concern. We compared the response to BNT162b2 mRNA vaccinations of patients with multiple myeloma (MM, n = 60) or Waldenstrom’s macroglobulinemia (WM, n = 20) with healthy vaccine recipients (n = 37). Patient cohorts on active therapy affecting B cell development had impaired binding and neutralizing antibody (NAb) response rate and magnitude, including several patients lacking responses, even after a 3rd vaccine dose, whereas non-B cell depleting therapies had a lesser effect. In contrast, MM and WM cohorts off-therapy showed increased NAb with a broad response range. ELISA Spike-Receptor Binding Domain (RBD) Ab titers in healthy vaccine recipients and patient cohorts were good predictors of the ability to neutralize not only the original WA1 but also the most divergent Omicron variants BA.4/5. Compared to WA1, significantly lower NAb responses to BA.4/5 were found in all patient cohorts on-therapy. In contrast, the MM and WM cohorts off-therapy showed a higher probability to neutralize BA.4/5 after the 3rd vaccination. Overall, the boost in NAb after the 3rd dose suggests that repeat vaccination of MM and WM patients is beneficial even under active therapy.

Dataset Information

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

Publications

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

Similar Datasets

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