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. 2025 Apr 4;272(4):314.
doi: 10.1007/s00415-025-13027-x.

Recall vaccination increases detectable B-cell reactivity in persons with multiple sclerosis treated with ocrelizumab

Lucia Moiola  1 , Alessandra Mandelli  2 , Maciej Tarkowski  3 , Annamaria Finardi  2 , Arianna Gabrieli  3 , Chiara Zanetta  1 , Vittorio Viti  1 , Irene Gattuso  1 , Federica Esposito  1 , Rosetta Pedotti  4 , Erwan Muros-Le Rouzic  4 , Catarina Raposo  4 , Maria A Rocca  1   5   6 , Massimo Locatelli  7 , Chiara Bonini  6   8 , Roberto Furlan  9   10 , Agostino Riva  3   11 , Massimo Filippi  1   6   12   13
Affiliations

Recall vaccination increases detectable B-cell reactivity in persons with multiple sclerosis treated with ocrelizumab

Lucia Moiola et al. J Neurol. .

Abstract

Background: Utility of repeated boosts of anti-SARS-CoV-2 vaccination in persons with MS (pwMS) treated with ocrelizumab is questioned.

Objective: Investigate antiviral antibody and T-cell responses after mRNA vaccination for SARS-CoV-2 in ocrelizumab-treated pwMS.

Methods: Peripheral blood mononuclear cells were stimulated with SARS-CoV-2 peptide pools and T-cell reactivity was assessed by ELISPOT for IFN-γ detection, and by multiparametric flow cytometry analyses for assessment and characterization of T-cell activation. Anti-SARS-CoV-2 spike and nucleocapsid antibodies were analyzed in plasma of pwMS using two commercial platforms.

Results: ELISPOT assay against the spike protein of SARS-CoV-2 showed that COVID vaccination with mRNA results in the development of a robust specific T-cell reactivity that is sustained over repeated cycles of vaccination and tends to decline 2 years after last boost. Flow cytometry analysis following stimulation with SARS-CoV-2 peptide pools confirmed the presence of CD8+ T memory stem cells. CD8+ T memory stem cells, in particular, increased after repeated boosts of vaccination, as occurred for anti-SARS-CoV-2 antibodies.

Conclusions: Repeated cycles of vaccination increase T and B-cell reactivity against SARS-CoV-2.

Keywords: Anti-CD20; COVID-19; Multiple sclerosis; Ocrelizumab; SARS-CoV-2; Vaccination.

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Conflict of interest statement

Declarations. Conflicts of interest: The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: L.M., C.Z, F.E., M.A.R., M.L., R.F., and M.F. received honoraria as speaker or board member from Roche. R.P., E.M., and C.R. are employees of Hoffman-La Roche. Ethical standard statement: The protocol and consent documents were approved by appropriate independent ethics committees at National Institute for Infectious Diseases “Lazzaro Spallanzani” IRCCS. Informed consent: All participants provided written informed consent.

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