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A Paratope-Enhanced Method to Determine Breadth and Depth TCR Clonal Metrics of the Private Human T-Cell Vaccine Response after SARS-CoV-2 Vaccination

Quantitative metrics for vaccine-induced T-cell responses are an important need for developing correlates of protection and their use in vaccine-based medical management and population health. Molecular TCR analysis is an appealing strategy but currently requires a targeted methodology involving com...

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Autores principales: Li, Dalin, Pavlovitch-Bedzyk, Ana Jimena, Ebinger, Joseph E., Khan, Abdul, Hamideh, Mohamed, Merchant, Akil, Figueiredo, Jane C., Cheng, Susan, Davis, Mark M., McGovern, Dermot P. B., Melmed, Gil Y., Xu, Alexander M., Braun, Jonathan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10531868/
https://www.ncbi.nlm.nih.gov/pubmed/37762524
http://dx.doi.org/10.3390/ijms241814223
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author Li, Dalin
Pavlovitch-Bedzyk, Ana Jimena
Ebinger, Joseph E.
Khan, Abdul
Hamideh, Mohamed
Merchant, Akil
Figueiredo, Jane C.
Cheng, Susan
Davis, Mark M.
McGovern, Dermot P. B.
Melmed, Gil Y.
Xu, Alexander M.
Braun, Jonathan
author_facet Li, Dalin
Pavlovitch-Bedzyk, Ana Jimena
Ebinger, Joseph E.
Khan, Abdul
Hamideh, Mohamed
Merchant, Akil
Figueiredo, Jane C.
Cheng, Susan
Davis, Mark M.
McGovern, Dermot P. B.
Melmed, Gil Y.
Xu, Alexander M.
Braun, Jonathan
author_sort Li, Dalin
collection PubMed
description Quantitative metrics for vaccine-induced T-cell responses are an important need for developing correlates of protection and their use in vaccine-based medical management and population health. Molecular TCR analysis is an appealing strategy but currently requires a targeted methodology involving complex integration of ex vivo data (antigen-specific functional T-cell cytokine responses and TCR molecular responses) that uncover only public antigen-specific metrics. Here, we describe an untargeted private TCR method that measures breadth and depth metrics of the T-cell response to vaccine challenge using a simple pre- and post-vaccine subject sampling, TCR immunoseq analysis, and a bioinformatic approach using self-organizing maps and GLIPH2. Among 515 subjects undergoing SARS-CoV-2 mRNA vaccination, we found that breadth and depth metrics were moderately correlated between the targeted public TCR response and untargeted private TCR response methods. The untargeted private TCR method was sufficiently sensitive to distinguish subgroups of potential clinical significance also observed using public TCR methods (the reduced T-cell vaccine response with age and the paradoxically elevated T-cell vaccine response of patients on anti-TNF immunotherapy). These observations suggest the promise of this untargeted private TCR method to produce T-cell vaccine-response metrics in an antigen-agnostic and individual-autonomous context.
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spelling pubmed-105318682023-09-28 A Paratope-Enhanced Method to Determine Breadth and Depth TCR Clonal Metrics of the Private Human T-Cell Vaccine Response after SARS-CoV-2 Vaccination Li, Dalin Pavlovitch-Bedzyk, Ana Jimena Ebinger, Joseph E. Khan, Abdul Hamideh, Mohamed Merchant, Akil Figueiredo, Jane C. Cheng, Susan Davis, Mark M. McGovern, Dermot P. B. Melmed, Gil Y. Xu, Alexander M. Braun, Jonathan Int J Mol Sci Article Quantitative metrics for vaccine-induced T-cell responses are an important need for developing correlates of protection and their use in vaccine-based medical management and population health. Molecular TCR analysis is an appealing strategy but currently requires a targeted methodology involving complex integration of ex vivo data (antigen-specific functional T-cell cytokine responses and TCR molecular responses) that uncover only public antigen-specific metrics. Here, we describe an untargeted private TCR method that measures breadth and depth metrics of the T-cell response to vaccine challenge using a simple pre- and post-vaccine subject sampling, TCR immunoseq analysis, and a bioinformatic approach using self-organizing maps and GLIPH2. Among 515 subjects undergoing SARS-CoV-2 mRNA vaccination, we found that breadth and depth metrics were moderately correlated between the targeted public TCR response and untargeted private TCR response methods. The untargeted private TCR method was sufficiently sensitive to distinguish subgroups of potential clinical significance also observed using public TCR methods (the reduced T-cell vaccine response with age and the paradoxically elevated T-cell vaccine response of patients on anti-TNF immunotherapy). These observations suggest the promise of this untargeted private TCR method to produce T-cell vaccine-response metrics in an antigen-agnostic and individual-autonomous context. MDPI 2023-09-18 /pmc/articles/PMC10531868/ /pubmed/37762524 http://dx.doi.org/10.3390/ijms241814223 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Li, Dalin
Pavlovitch-Bedzyk, Ana Jimena
Ebinger, Joseph E.
Khan, Abdul
Hamideh, Mohamed
Merchant, Akil
Figueiredo, Jane C.
Cheng, Susan
Davis, Mark M.
McGovern, Dermot P. B.
Melmed, Gil Y.
Xu, Alexander M.
Braun, Jonathan
A Paratope-Enhanced Method to Determine Breadth and Depth TCR Clonal Metrics of the Private Human T-Cell Vaccine Response after SARS-CoV-2 Vaccination
title A Paratope-Enhanced Method to Determine Breadth and Depth TCR Clonal Metrics of the Private Human T-Cell Vaccine Response after SARS-CoV-2 Vaccination
title_full A Paratope-Enhanced Method to Determine Breadth and Depth TCR Clonal Metrics of the Private Human T-Cell Vaccine Response after SARS-CoV-2 Vaccination
title_fullStr A Paratope-Enhanced Method to Determine Breadth and Depth TCR Clonal Metrics of the Private Human T-Cell Vaccine Response after SARS-CoV-2 Vaccination
title_full_unstemmed A Paratope-Enhanced Method to Determine Breadth and Depth TCR Clonal Metrics of the Private Human T-Cell Vaccine Response after SARS-CoV-2 Vaccination
title_short A Paratope-Enhanced Method to Determine Breadth and Depth TCR Clonal Metrics of the Private Human T-Cell Vaccine Response after SARS-CoV-2 Vaccination
title_sort paratope-enhanced method to determine breadth and depth tcr clonal metrics of the private human t-cell vaccine response after sars-cov-2 vaccination
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10531868/
https://www.ncbi.nlm.nih.gov/pubmed/37762524
http://dx.doi.org/10.3390/ijms241814223
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