Durable T cell immunity to COVID-19 vaccines in MS patients on B cell depletion therapy
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<sup>+</sup> and CD8<sup>+</sup> 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.
Authors
- Wen Zhu (ORCID: https://orcid.org/0000-0003-0832-2453)
- Dina Jacobs (ORCID: https://orcid.org/0009-0005-6555-8712)
- Diego A. Espinoza (ORCID: https://orcid.org/0000-0002-9627-6508)
- Elizabeth Walker (ORCID: https://orcid.org/0000-0002-6294-1098)
- Mihir Kakara (ORCID: https://orcid.org/0000-0001-8951-8604)
- Joseph J. Sabatino (ORCID: https://orcid.org/0000-0002-6804-7441)
- Julia Davis‐Porada (ORCID: https://orcid.org/0000-0001-9313-4590)
- Ceren Tozlu (ORCID: https://orcid.org/0000-0002-6828-886X)
- Philip L. De Jager (ORCID: https://orcid.org/0000-0002-8057-2505)
- Riley M. Bove (ORCID: https://orcid.org/0000-0002-2034-8800)
- Adelle Ricci
- Kaho Onomichi
- E. John Wherry (ORCID: https://orcid.org/0000-0003-0477-1956)
- Claudia Aiello
- Donna L. Färber (ORCID: https://orcid.org/0000-0001-8236-9183)
- Zongqi Xia (ORCID: https://orcid.org/0000-0003-1500-2589)
- Amit Bar‐Or (ORCID: https://orcid.org/0000-0001-7179-0335)
- Rebecca Straus Farber
- Sokratis A. Apostolidis (ORCID: https://orcid.org/0000-0002-0224-0097)
- Sugeidy Ferreira Brito
- Lili Zhang (ORCID: https://orcid.org/0000-0002-9022-0327)
- Sarah F. Wesley
Institutions
- University of Pittsburgh (US)
- University of California, San Francisco (US)
- Cornell University (US)
- Columbia University Irving Medical Center (US)
- Translational Therapeutics (United States) (US)
- Weill Cornell Medicine (US)
- New York University (US)
- Columbia University (US)
- University of Pennsylvania (US)
Publication Details
- Journal
- npj Vaccines
- Published
- 2025-05-17
- DOI
- https://doi.org/10.1038/s41541-025-01151-8
- Citations
- 2
- Primary Topic
- SARS-CoV-2 and COVID-19 Research
- Type
- article
- Field-Weighted Citation Impact
- 2.79
Funders
- U.S. Department of Defense
- National Multiple Sclerosis Society
- Amgen
- Eli Lilly and Company
- GlaxoSmithKline
- Sanofi
- Biogen
- Alexion Pharmaceuticals
- Celgene
- University of Pennsylvania
- Novartis Pharmaceuticals Corporation
- TG Therapeutics
- Atara Biotherapeutics
- Horizon Therapeutics
- Multiple Sclerosis Society of Canada
- Multiple Sclerosis Society
- Novo Nordisk
- National Institutes of Health
- Genentech
- EMD Serono
- Sanofi Genzyme
- Canadian Institutes of Health Research
- National Institute of Allergy and Infectious Diseases