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Humoral and T-Cell Response to SARS-CoV-2 Vaccination in Patients With Multiple Sclerosis Treated With Ocrelizumab

Educational Objective
To identify the key insights or developments described in this article
1 Credit CME
Key Points

Question  Do patients with multiple sclerosis treated with the B-cell–depleting agent ocrelizumab develop T-cell and humoral responses to the SARS-CoV-2 messenger RNA vaccine?

Findings  In this cohort study of 112 participants, those treated with ocrelizumab developed lower serology response compared with untreated patients and healthy controls but showed preserved T-cell response to the SARS-CoV-2 vaccine compared with healthy controls.

Meaning  In this study, preserved vaccine-specific T-cell responses in patients with multiple sclerosis treated with ocrelizumab are reassuring and will help to develop therapeutic strategies in patients with multiple sclerosis during the COVID-19 pandemic.


Importance  B-cell–depleting therapies may affect the development of a protective immune response following vaccination. Understanding the ability to develop vaccine-specific immunity to COVID-19 in patients with multiple sclerosis (MS) treated with B-cell–depleting therapy is of importance for clinical decisions.

Objective  To assess SARS-CoV-2 vaccine-specific humoral and cellular responses in patients treated with ocrelizumab compared with healthy controls.

Design, Setting, and Participants  This single-center study performed at Hadassah Medical Center in Jerusalem, Israel, included patients with MS treated with ocrelizumab, healthy controls, and untreated patients with MS. Vaccination occurred between December 2020 and April 2021. Participants donated blood 2 to 4 and 2 to 8 weeks after the second vaccine dose for antibody and T-cell assessments, respectively.

Exposures  All participants received 2 doses of BNT162b2 vaccine (Pfizer/BioNTech) and completed the study.

Main Outcomes and Measures  Proportion of patients treated with ocrelizumab with SARS-CoV-2–specific serology and/or T-cell responses following vaccination. All participants underwent SARS-CoV-2 antibody testing; 29 patients treated with ocrelizumab and 15 healthy controls had evaluation of SARS-CoV-2–specific T-cell responses.

Results  Of 112 participants, 49 (43.8%) had MS and were treated with ocrelizumab (33 [67.3%] female; mean [SD] age, 47.9 [13.3] years), 23 (20.5%) had MS and were not treated with disease-modifying therapies (18 [78.3%] female; mean [SD] age, 49 [13.4] years), and 40 (35.7%) were healthy controls (25 [62.5%] female; mean [SD] age, 45.3 [16] years). Twenty-six of 29 patients (89.7%) treated with ocrelizumab and 15 of 15 healthy controls (100%) had SARS-CoV-2–specific T cells following vaccination at similar levels (mean [SD], 15.4 [7.6] and 14.3 [6.3] spot-forming cells, respectively). Mean antibody titers and positive serology rate were lower in the group of patients treated with ocrelizumab (mean [SD] antibody titers and positive serology rate, 26.2 [49.2] and 376.5 [907.6] AU/mL; 10 of 40 [25%] and 20 of 49 [40.8%] for S1/S2 and receptor-binding domain, respectively) compared with healthy controls (mean [SD] antibody titers and positive serology rate, 283 [100] and 12 712 [9114] AU/mL; 100% S1/S2 and receptor-binding domain) and untreated patients (mean [SD] antibody titers and positive serology rate, 288.3 [113.8] and 10 877 [9476] AU/mL; 100% S1/S2 and receptor-binding domain), with positive association to time from ocrelizumab infusion (S1/S2: r = 0.7, P < .001; receptor-binding domain: r = 0.4, P = .04).

Conclusion and Relevance  In this study, patients with MS who were treated with ocrelizumab generated comparable SARS-CoV-2–specific T-cell responses with healthy controls and had lower antibody response following vaccination. Given the potential role of T cells in protection from severe disease, this is reassuring and will help physicians develop consensus guidelines regarding MS treatment in the era of the COVID-19 pandemic.

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Article Information

Corresponding Author: Adi Vaknin-Dembinsky, MD, PhD, Neurology Department, Multiple Sclerosis & Immunobiology Research, Hadassah Medical Center, Ein–Kerem, PO Box 12000, Jerusalem 91120, Israel (adembinsky@gmail.com).

Accepted for Publication: August 24, 2021.

Published Online: September 23, 2021. doi:10.1001/jamaneurol.2021.3599

Author Contributions: Drs Vaknin-Dembinsky and Brill had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Brill, Raposo, Vaknin-Dembinsky.

Acquisition, analysis, or interpretation of data: All authors.

Drafting of the manuscript: Brill, Haham, Oiknine-Djian, Vaknin-Dembinsky.

Critical revision of the manuscript for important intellectual content: Brill, Rechtman, Zveik, Wolf, Levin, Raposo, Vaknin-Dembinsky.

Statistical analysis: Brill, Rechtman, Zveik.

Administrative, technical, or material support: Brill, Haham, Oiknine-Djian, Raposo, Vaknin-Dembinsky.

Supervision: Wolf, Levin, Vaknin-Dembinsky.

Conflict of Interest Disclosures: Dr Raposo is an employee and shareholder of F. Hoffmann-La Roche Ltd. Dr Vaknin-Dembinsky reported grants from F. Hoffmann-La Roche Ltd during the conduct of the study; personal fees from Roche, Biogen, Genzyme Sanofi, Merck, and Novartis outside the submitted work; and grants from Merck and the Ministry of Health of Israel outside the submitted work. No other disclosures were reported.

Funding/Support: This work was partially supported by F. Hoffmann-La Roche Ltd, which developed and markets ocrelizumab.

Role of the Funder/Sponsor: The funder had a role in the design of the study and review of the manuscript. The funder had no role in the conduct of the study; collection, management, or analysis of the data; preparation or approval of the manuscript; and decision to submit the manuscript for publication.

Additional Contributions: We thank all patients who generously donated blood samples and our study nurse Michal Mor, LSN (Hadassah Medical Center). We also thank Sharon Ehrlich, MD (Roche Pharmaceuticals Ltd [Israel]), and Rosetta Pedotti, MD, PhD, Nikki Jessop, MD, and Erwan Muros, MPH (F. Hoffmann-La Roche Ltd), for the scientific discussions and support reviewing the manuscript. No compensation was received.

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  • 1.00 CME points in the American Board of Surgery’s (ABS) Continuing Certification program

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