Immune response in ofatumumab treated multiple sclerosis patients after SARS-CoV-2 vaccination
- \(\bf Objective:\) The pandemic induced by SARS-CoV-2 has huge implications for patients with immunosuppression that is caused by disorders or specific treatments. Especially approaches targeting B cells \(\it via\) anti-CD20 therapy are associated with impaired humoral immune response but sustained cellular immunity. Ofatumumab is a human anti-CD20 directed antibody applied in low dosages subcutaneously, recently licensed for Multiple Sclerosis (MS). Effects of early ofatumumab treatment on alterations of immune cell composition and immune response towards SARS-CoV-2 are incompletely understood. \(\bf Methods:\) We here investigated immune cell alterations in early ofatumumab (Ofa) treated patients and effects on humoral (titer, neutralization capacity against wild type, Delta and Omicron) and cellular immune responses in Ofa treated MS patients following a third vaccination against SARS-CoV-2 compared to healthy controls. \(\bf Results:\) We show that a mean treatment duration of three months in the Ofa group led to near complete B cell depletion in line with altered composition of certain \(CD4^{+}\) T cell subpopulations such as enhanced frequencies of naive and a decrease of non-suppressive regulatory T cells (Tregs). Titer and neutralization capacity against SARS-CoV-2 variants was impaired while cellular immune response was sustained, characterized by a strong T helper 1 profile (Th1). \(\bf Interpretation:\) In summary, low dosage ofatumumab treatment elicits sustained depletion of B cells in line with alterations of immune cells, mainly Tregs. This is associated with impaired humoral immune response towards SARS-CoV-2 vaccination but preserved, Th1 driven cellular immunity adding crucial information regarding early effects of low dosage anti-CD20 therapy on humoral and cellular immunity.
Author: | Simon Raoul FaissnerORCiDGND, Neele HeitmannGND, Carlos Plaza SirventORCiDGND, Paulina TrendelenburgGND, Ulaş CeylanGND, Jeremias MotteORCiDGND, Clara BessenGND, Doris UrlaubGND, Carsten WatzlORCiDGND, Oliver OverheuORCiDGND, Anke Claudia Reinacher-SchickORCiDGND, Kerstin HellwigORCiDGND, Stephanie PfänderORCiDGND, Ingo SchmitzORCiDGND, Ralf GoldORCiDGND |
---|---|
URN: | urn:nbn:de:hbz:294-102653 |
DOI: | https://doi.org/10.3389/fimmu.2022.980526 |
Parent Title (English): | Frontiers in immunology |
Publisher: | Frontiers Media |
Place of publication: | Lausanne, Schweiz |
Document Type: | Article |
Language: | English |
Date of Publication (online): | 2023/10/20 |
Date of first Publication: | 2022/08/31 |
Publishing Institution: | Ruhr-Universität Bochum, Universitätsbibliothek |
Tag: | Open Access Fonds SARS-CoV-2 vaccination; T cell response; anti-CD20 therapy; humoral immune response; multiple sclerosis; ofatumumab |
Volume: | 13 |
Issue: | Article 980526 |
First Page: | 980526-1 |
Last Page: | 980526-13 |
Note: | Article Processing Charge funded by the Deutsche Forschungsgemeinschaft (DFG) and the Open Access Publication Fund of Ruhr-Universität Bochum. |
Institutes/Facilities: | St. Josef-Hospital Bochum, Neurologische Klinik |
Dewey Decimal Classification: | Technik, Medizin, angewandte Wissenschaften / Medizin, Gesundheit |
open_access (DINI-Set): | open_access |
Licence (English): | Creative Commons - CC BY 4.0 - Attribution 4.0 International |