Durable T cell immunity to COVID-19 vaccines in MS patients on B cell depletion therapy

Abstract Immune-mediated protection generated to COVID-19 mRNA vaccines is associated with anti-Spike (S) protein neutralizing antibodies. However, humoral immunity is compromised in B cell depleting (BCD) therapies, used to treat autoimmune diseases such as Multiple Sclerosis (MS). To study the eff...

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Main Authors: Julia Davis-Porada, Ceren Tozlu, Claudia Aiello, Sokratis A. Apostolidis, Amit Bar-Or, Riley Bove, Diego A. Espinoza, Sugeidy Ferreira Brito, Dina Jacobs, Mihir Kakara, Kaho Onomichi, Adelle Ricci, Joseph J. Sabatino, Elizabeth Walker, E. John Wherry, Lili Zhang, Wen Zhu, Zongqi Xia, Philip De Jager, Sarah Flanagan Wesley, Rebecca Straus Farber, Donna L. Farber
Format: Article
Language:English
Published: Nature Portfolio 2025-05-01
Series:npj Vaccines
Online Access:https://doi.org/10.1038/s41541-025-01151-8
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author Julia Davis-Porada
Ceren Tozlu
Claudia Aiello
Sokratis A. Apostolidis
Amit Bar-Or
Riley Bove
Diego A. Espinoza
Sugeidy Ferreira Brito
Dina Jacobs
Mihir Kakara
Kaho Onomichi
Adelle Ricci
Joseph J. Sabatino
Elizabeth Walker
E. John Wherry
Lili Zhang
Wen Zhu
Zongqi Xia
Philip De Jager
Sarah Flanagan Wesley
Rebecca Straus Farber
Donna L. Farber
author_facet Julia Davis-Porada
Ceren Tozlu
Claudia Aiello
Sokratis A. Apostolidis
Amit Bar-Or
Riley Bove
Diego A. Espinoza
Sugeidy Ferreira Brito
Dina Jacobs
Mihir Kakara
Kaho Onomichi
Adelle Ricci
Joseph J. Sabatino
Elizabeth Walker
E. John Wherry
Lili Zhang
Wen Zhu
Zongqi Xia
Philip De Jager
Sarah Flanagan Wesley
Rebecca Straus Farber
Donna L. Farber
author_sort Julia Davis-Porada
collection DOAJ
description Abstract Immune-mediated protection generated to COVID-19 mRNA vaccines is associated with anti-Spike (S) protein neutralizing antibodies. However, humoral immunity is compromised in B cell depleting (BCD) therapies, used to treat autoimmune diseases such as Multiple Sclerosis (MS). To study the effect of BCD on the durability and protective efficacy of vaccine-induced immunity, we evaluated S-reactive antibodies and T cell responses 1–70 weeks post-vaccination in MS cohorts treated with BCD compared to non-BCD therapies from four centers. BCD-treated participants had significantly reduced antibody levels and enhanced frequencies of S-reactive CD4+ and CD8+ memory T cells to COVID-19 vaccination compared to the non-BCD group, with some variations among different BCD formulations. T cell memory responses persisted up to 14 months post-vaccination in both BCD and non-BCD cohorts, who experienced similar clinical protection from COVID-19. Together, our results establish a critical role for T cell-mediated immunity in anti-viral protection independent of humoral immunity.
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spelling doaj-art-73ffc40c3e5a4c1fb276971d5836fc882025-08-20T01:52:03ZengNature Portfolionpj Vaccines2059-01052025-05-0110111010.1038/s41541-025-01151-8Durable T cell immunity to COVID-19 vaccines in MS patients on B cell depletion therapyJulia Davis-Porada0Ceren Tozlu1Claudia Aiello2Sokratis A. Apostolidis3Amit Bar-Or4Riley Bove5Diego A. Espinoza6Sugeidy Ferreira Brito7Dina Jacobs8Mihir Kakara9Kaho Onomichi10Adelle Ricci11Joseph J. Sabatino12Elizabeth Walker13E. John Wherry14Lili Zhang15Wen Zhu16Zongqi Xia17Philip De Jager18Sarah Flanagan Wesley19Rebecca Straus Farber20Donna L. Farber21Department of Microbiology and Immunology, Columbia University Irving Medical CenterDepartment of Radiology, Weill Cornell MedicineDepartment of Microbiology and Immunology, Columbia University Irving Medical CenterInstitute for Immunology and Immune Health, University of Pennsylvania Perelman School of MedicineCenter for Neuroinflammation and Experimental Therapeutics, University of Pennsylvania Perelman School of MedicineUCSF Weill Institute for Neuroscience, Department of Neurology, University of California San FranciscoCenter for Neuroinflammation and Experimental Therapeutics, University of Pennsylvania Perelman School of MedicineDepartment of Neurology, Columbia University Vagelos College of Physicians and Surgeons, Neurology, Columbia Multiple Sclerosis Center and Center for Translational & Computational NeuroimmunologyCenter for Neuroinflammation and Experimental Therapeutics, University of Pennsylvania Perelman School of MedicineDepartment of Neurology, NYU Grossman School of MedicineDepartment of Neurology, Columbia University Vagelos College of Physicians and Surgeons, Neurology, Columbia Multiple Sclerosis Center and Center for Translational & Computational NeuroimmunologyDepartment of Neurology, Columbia University Vagelos College of Physicians and Surgeons, Neurology, Columbia Multiple Sclerosis Center and Center for Translational & Computational NeuroimmunologyUCSF Weill Institute for Neuroscience, Department of Neurology, University of California San FranciscoDepartment of Neurology, University of PittsburghInstitute for Immunology and Immune Health, University of Pennsylvania Perelman School of MedicineDepartment of Neurology, University of PittsburghDepartment of Neurology, University of PittsburghDepartment of Neurology, University of PittsburghDepartment of Neurology, Columbia University Vagelos College of Physicians and Surgeons, Neurology, Columbia Multiple Sclerosis Center and Center for Translational & Computational NeuroimmunologyDepartment of Neurology, Columbia University Vagelos College of Physicians and Surgeons, Neurology, Columbia Multiple Sclerosis Center and Center for Translational & Computational NeuroimmunologyDepartment of Neurology, Columbia University Vagelos College of Physicians and Surgeons, Neurology, Columbia Multiple Sclerosis Center and Center for Translational & Computational NeuroimmunologyDepartment of Microbiology and Immunology, Columbia University Irving Medical CenterAbstract Immune-mediated protection generated to COVID-19 mRNA vaccines is associated with anti-Spike (S) protein neutralizing antibodies. However, humoral immunity is compromised in B cell depleting (BCD) therapies, used to treat autoimmune diseases such as Multiple Sclerosis (MS). To study the effect of BCD on the durability and protective efficacy of vaccine-induced immunity, we evaluated S-reactive antibodies and T cell responses 1–70 weeks post-vaccination in MS cohorts treated with BCD compared to non-BCD therapies from four centers. BCD-treated participants had significantly reduced antibody levels and enhanced frequencies of S-reactive CD4+ and CD8+ memory T cells to COVID-19 vaccination compared to the non-BCD group, with some variations among different BCD formulations. T cell memory responses persisted up to 14 months post-vaccination in both BCD and non-BCD cohorts, who experienced similar clinical protection from COVID-19. Together, our results establish a critical role for T cell-mediated immunity in anti-viral protection independent of humoral immunity.https://doi.org/10.1038/s41541-025-01151-8
spellingShingle Julia Davis-Porada
Ceren Tozlu
Claudia Aiello
Sokratis A. Apostolidis
Amit Bar-Or
Riley Bove
Diego A. Espinoza
Sugeidy Ferreira Brito
Dina Jacobs
Mihir Kakara
Kaho Onomichi
Adelle Ricci
Joseph J. Sabatino
Elizabeth Walker
E. John Wherry
Lili Zhang
Wen Zhu
Zongqi Xia
Philip De Jager
Sarah Flanagan Wesley
Rebecca Straus Farber
Donna L. Farber
Durable T cell immunity to COVID-19 vaccines in MS patients on B cell depletion therapy
npj Vaccines
title Durable T cell immunity to COVID-19 vaccines in MS patients on B cell depletion therapy
title_full Durable T cell immunity to COVID-19 vaccines in MS patients on B cell depletion therapy
title_fullStr Durable T cell immunity to COVID-19 vaccines in MS patients on B cell depletion therapy
title_full_unstemmed Durable T cell immunity to COVID-19 vaccines in MS patients on B cell depletion therapy
title_short Durable T cell immunity to COVID-19 vaccines in MS patients on B cell depletion therapy
title_sort durable t cell immunity to covid 19 vaccines in ms patients on b cell depletion therapy
url https://doi.org/10.1038/s41541-025-01151-8
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