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

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

doi:10.1016/j.isci.2022.105209

Cited by 6 publications

(3 citation statements)

References 72 publications

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“…These individuals were shown to have altered specific B cells and less diversity in the specific T cell receptor (TCR) repertoire. The single-cell transcriptomic assessment demonstrated the activation of aging pathways, which may demonstrate that premature aging of lymphocytes contributes to poor vaccineinduced immunity (36). Our results are consistent with these observations, showing chronological age as the main clinical factor of poor response to vaccination, but also that immuneaging of T-cells repertoire impacts the vaccine efficacy.…”

Section: Discussionsupporting

confidence: 89%

The presence of senescent peripheral T-cells is negatively correlated to COVID-19 vaccine-induced immunity in cancer patients under 70 years of age

et al. 2023

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PurposeCancer patients are at risk of severe COVID-19 infection, and vaccination is recommended. Nevertheless, we observe a failure of COVID-19 vaccines in this vulnerable population. We hypothesize that senescent peripheral T-cells alter COVID-19 vaccine-induced immunity.MethodsWe performed a monocentric prospective study and enrolled cancer patients and healthy donors before the COVID-19 vaccination. The primary objective was to assess the association of peripheral senescent T-cells (CD28-CD57+KLRG1+) with COVID-19 vaccine-induced immunity.ResultsEighty cancer patients have been included, with serological and specific T-cell responses evaluated before and at 3 months post-vaccination. Age ≥ 70 years was the principal clinical factor negatively influencing the serological (p=0.035) and specific SARS-CoV-2 T-cell responses (p=0.047). The presence of senescent T-cells was correlated to lower serological (p=0.049) and specific T-cell responses (p=0.009). Our results sustained the definition of a specific cut-off for senescence immune phenotype (SIP) (≥ 5% of CD4 and ≥ 39.5% of CD8 T-cells), which was correlated to a lower serological response induced by COVID-19 vaccination for CD4 and CD8 SIPhigh (p=0.039 and p=0.049 respectively). While CD4 SIP level had no impact on COVID-19 vaccine efficacy in elderly patients, our results unraveled a possible predictive role for CD4 SIPhigh T-cell levels in younger cancer patients.ConclusionsElderly cancer patients have a poor serological response to vaccination; specific strategies are needed in this population. Also, the presence of a CD4 SIPhigh affects the serological response in younger patients and seems to be a potential biomarker of no vaccinal response.

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Section: Discussionsupporting

confidence: 89%

The presence of senescent peripheral T-cells is negatively correlated to COVID-19 vaccine-induced immunity in cancer patients under 70 years of age

et al. 2023

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“…IBD cohort plasma samples consisted of IBD subjects (n=205) collected as outline in Kumar et al . 50 along with age and sex matched controls (n=287) from the relatively healthy health care worker cohort, Corale 51,52 . Supplemental table 4 lists the sex, age and race characteristics of IBDs and controls.…”

Section: Methodsmentioning

confidence: 99%

“…Both cohorts were initially designed to study the effect of SARS-COVID-2 vaccines and received two doses of mRNA vaccine as per local department of health guidelines and institutional policies, and the samples were collected 16 weeks after the 2nd dose of COVID vaccine in both cohorts. IBD cohort plasma samples consisted of IBD subjects (n=205) collected as outline in Kumar et al 50 along with age and sex matched controls (n=287) from the relatively healthy health care worker cohort, Corale 51,52 . Supplemental table 4 lists the sex, age and race characteristics of IBDs and controls.…”

Section: Plasma Samplesmentioning

confidence: 99%

Paradigm shift in biomarker translation: a pipeline to generate clinical grade biomarker candidates from DIA-MS discovery

Fu,

Vegesna,

Sundararaman

et al. 2024

Preprint

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Clinical biomarker development has been stymied by inaccurate protein quantification from mass spectrometry (MS) discovery data and a prolonged validation process. To mitigate these issues, we created the Targeted Extraction Assessment of Quantification (TEAQ) software package. This innovative tool uses the discovery cohort analysis to select precursors, peptides, and proteins that adhere to established targeted assay criteria. TEAQ was applied to Data-Independent Acquisition MS data from plasma samples acquired on an OrbitrapTM AstralTM MS. Identified precursors were evaluated for linearity, specificity, repeatability, reproducibility, and intra-protein correlation from 11-point loading curves under three throughputs, to develop a resource for clinical-grade targeted assays. From a clinical cohort of individuals with inflammatory bowel disease (n=492), TEAQ successfully identified 1116 signature peptides for 327 quantifiable proteins from 1180 identified proteins. Embedding stringent selection criteria adaptable to targeted assay development into the analysis of discovery data will streamline the transition to validation and clinical studies.

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A Proteomics Pipeline for Generating Clinical Grade Biomarker Candidates from Data‐Independent Acquisition Mass Spectrometry (DIA‐MS) Discovery

Fu,

Vegesna,

Sundararaman

et al. 2024

Angewandte Chemie

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Clinical biomarker development has been stymied by inaccurate protein quantification from mass spectrometry (MS) discovery data and a prolonged validation process. To mitigate these issues, we created the Targeted Extraction Assessment of Quantification (TEAQ) software package that uses data‐independent acquisition analysis from a discovery cohort to select precursors, peptides, and proteins that adhere to analytical criteria required for established targeted assays. TEAQ was applied to DIA‐MS data from plasma samples acquired on a new high resolution accurate mass (HRAM) mass spectrometry platform where precursors were evaluated for linearity, specificity, repeatability, reproducibility, and intra‐protein correlation based on 8‐ or 11‐point loading curves at three throughputs. This data can be used as a general resource for developing other targeted assays. TEAQ analysis of data from a case and control cohort for inflammatory bowel disease (n=492) identified 1110 signature peptides for 326 quantifiable proteins from the 1179 identified proteins. Applying TEAQ analysis to discovery data will streamline targeted assay development and the transition to validation and clinical studies.

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

Cited by 6 publications

References 72 publications

The presence of senescent peripheral T-cells is negatively correlated to COVID-19 vaccine-induced immunity in cancer patients under 70 years of age

The presence of senescent peripheral T-cells is negatively correlated to COVID-19 vaccine-induced immunity in cancer patients under 70 years of age

Paradigm shift in biomarker translation: a pipeline to generate clinical grade biomarker candidates from DIA-MS discovery

A Proteomics Pipeline for Generating Clinical Grade Biomarker Candidates from Data‐Independent Acquisition Mass Spectrometry (DIA‐MS) Discovery

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