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SARS-CoV-2 mRNA vaccinations fail to elicit humoral and cellular immune responses in patients with multiple sclerosis receiving fingolimod

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Item Type:Article
Title:SARS-CoV-2 mRNA vaccinations fail to elicit humoral and cellular immune responses in patients with multiple sclerosis receiving fingolimod
Creators Name:Meyer-Arndt, L. and Braun, J. and Fauchere, F. and Vanshylla, K. and Loyal, L. and Henze, L. and Kruse, B. and Dingeldey, M. and Jürchott, K. and Mangold, M. and Maraj, A. and Braginets, A. and Böttcher, C. and Nitsche, A. and de la Rosa, K. and Ratswohl, C. and Sawitzki, B. and Holenya, P. and Reimer, U. and Sander, L.E. and Klein, F. and Paul, F. and Bellmann-Strobl, J. and Thiel, A. and Giesecke-Thiel, C.
Abstract:BACKGROUND: SARS-CoV-2 mRNA vaccination of healthy individuals is highly immunogenic and protective against severe COVID-19. However, there are limited data on how disease-modifying therapies (DMTs) alter SARS-CoV-2 mRNA vaccine immunogenicity in patients with autoimmune diseases. METHODS: As part of a prospective cohort study, we investigated the induction, stability and boosting of vaccine-specific antibodies, B cells and T cells in patients with multiple sclerosis (MS) on different DMTs after homologous primary, secondary and booster SARS-CoV-2 mRNA vaccinations. Of 126 patients with MS analysed, 105 received either anti-CD20-based B cell depletion (aCD20-BCD), fingolimod, interferon-β, dimethyl fumarate, glatiramer acetate, teriflunomide or natalizumab, and 21 were untreated MS patients for comparison. RESULTS: In contrast to all other MS patients, and even after booster, most aCD20-BCD- and fingolimod-treated patients showed no to markedly reduced anti-S1 IgG, serum neutralising activity and a lack of receptor binding domain-specific and S2-specific B cells. Patients receiving fingolimod additionally lacked spike-reactive CD4(+) T cell responses. The duration of fingolimod treatment, rather than peripheral blood B and T cell counts prior to vaccination, determined whether a humoral immune response was elicited. CONCLUSIONS: The lack of immunogenicity under long-term fingolimod treatment demonstrates that functional immune responses require not only immune cells themselves, but also access of these cells to the site of inoculation and their unimpeded movement. The absence of humoral and T cell responses suggests that fingolimod-treated patients with MS are at risk for severe SARS-CoV-2 infections despite booster vaccinations, which is highly relevant for clinical decision-making and adapted protective measures, particularly considering additional recently approved sphingosine-1-phosphate receptor antagonists for MS treatment.
Keywords:Clinical Neurology, Immunology, Infectious Diseases, Multiple Sclerosis
Source:Journal of Neurology Neurosurgery and Psychiatry
Publisher:BMJ Publishing Group
Page Range:960-971
Date:September 2022
Official Publication:https://doi.org/10.1136/jnnp-2022-329395
PubMed:View item in PubMed

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