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Immune response to SARS-CoV-2 mRNA vaccination in multiple sclerosis patients after rituximab treatment interruption
Umeå University, Faculty of Medicine, Department of Clinical Microbiology.ORCID iD: 0000-0001-5384-8038
Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
Umeå University, Faculty of Medicine, Department of Clinical Microbiology.ORCID iD: 0000-0003-2018-8592
Umeå University, Faculty of Medicine, Department of Clinical Microbiology. Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS). Umeå University, Faculty of Medicine, Wallenberg Centre for Molecular Medicine at Umeå University (WCMM).
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2023 (English)In: Frontiers in Immunology, E-ISSN 1664-3224, Vol. 14, article id 1219560Article in journal (Refereed) Published
Abstract [en]

Peripheral B cell depletion via anti-CD20 treatment is a highly effective disease-modifying treatment for reducing new relapses in multiple sclerosis (MS) patients. A drawback of rituximab (RTX) and other anti-CD20 antibodies is a poor immune response to vaccination. While this can be mitigated by treatment interruption of at least six months prior to vaccination, the timing to resume treatment while maintaining subsequent vaccine responses remains undetermined. Here, we characterized SARS-CoV-2 S-directed antibody and B cell responses throughout three BNT162b2 mRNA vaccine doses in RTX-treated MS patients, with the first two doses given during treatment interruption. We examined B-cell mediated immune responses in blood samples from patients with RTX-treated MS throughout three BNT162b2 vaccine doses, compared to an age- and sex-matched healthy control group. The first vaccine dose was given 1.3 years (median) after the last RTX infusion, the second dose one month after the first, and the third dose four weeks after treatment re-initiation. We analyzed SARS-CoV-2 S-directed antibody levels using enzyme-linked immunosorbent assay (ELISA), and the neutralization capacity of patient serum against SARS-CoV-2 S-pseudotyped lentivirus using luciferase reporter assay. In addition, we assessed switched memory (CD19+CD20+CD27+IgD-), unswitched memory (CD19+CD20+CD27+IgD+), naïve (CD19+CD20+CD27-IgD+), and double negative (DN, CD19+CD20+CD27-IgD-) B cell frequencies, as well as their SARS-CoV-2 S-specific (CoV+) and Decay Accelerating Factor-negative (DAF-) subpopulations, using flow cytometry. After two vaccine doses, S-binding antibody levels and neutralization capacity in SARS-CoV-2-naïve MS patients were comparable to vaccinated healthy controls, albeit with greater variation. Higher antibody response levels and CoV+-DN B cell frequencies after the second vaccine dose were predictive of a boost effect after the third dose, even after re-initiation of rituximab treatment. MS patients also exhibited lower frequencies of DAF- memory B cells, a suggested proxy for germinal centre activity, than control individuals. S-binding antibody levels in RTX-treated MS patients after two vaccine doses could help determine which individuals would need to move up their next vaccine booster dose or postpone their next RTX infusion. Our findings also offer first indications on the potential importance of antigenic stimulation of DN B cells and long-term impairment of germinal centre activity in rituximab-treated MS patients.

Place, publisher, year, edition, pages
Frontiers Media S.A., 2023. Vol. 14, article id 1219560
Keywords [en]
B cell immunology, COVID-19, multiple sclerosis, rituximab, vaccination
National Category
Infectious Medicine Immunology in the medical area
Identifiers
URN: urn:nbn:se:umu:diva-212992DOI: 10.3389/fimmu.2023.1219560PubMedID: 37575257Scopus ID: 2-s2.0-85167514064OAI: oai:DiVA.org:umu-212992DiVA, id: diva2:1789364
Funder
Region Västerbotten, RV-969133Swedish Research Council, 2020-0625Swedish Research Council, 2021-04665Knut and Alice Wallenberg Foundation, VA-2021-0018Knut and Alice Wallenberg Foundation, VA-2022-0008Science for Life Laboratory, SciLifeLabAvailable from: 2023-08-18 Created: 2023-08-18 Last updated: 2024-01-17Bibliographically approved

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Gröning, RemigiusDernstedt, AndyAhlm, ClasNormark, JohanSundström, PeterForsell, Mattias N. E.

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Gröning, RemigiusDernstedt, AndyAhlm, ClasNormark, JohanSundström, PeterForsell, Mattias N. E.
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Department of Clinical MicrobiologyMolecular Infection Medicine Sweden (MIMS)Wallenberg Centre for Molecular Medicine at Umeå University (WCMM)Neurosciences
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