• Lil Meyer-Arndt, Julian Braun, Florent Fauchere, Kanika Vanshylla, Lucie Loyal, Larissa Henze, Beate Kruse, Manuela Dingeldey, Karsten Jürchott, Maike Mangold, Ardit Maraj, Andre Braginets, Chotima Böttcher, Andreas Nitsche, Kathrin de la Rosa, Christoph Ratswohl, Birgit Sawitzki, Pavlo Holenya, Ulf Reimer, Leif E Sander, Florian Klein, Friedemann Paul, Judith Bellmann-Strobl, Andreas Thiel, and Claudia Giesecke-Thiel.
• Regenerative Immunology and Aging, BIH Immunomics, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
• J. Neurol. Neurosurg. Psychiatr. 2022 Sep 1; 93 (9): 960971960-971.

BackgroundSARS-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.MethodsAs 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.ResultsIn 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.ConclusionsThe 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.© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

24 keywords...

hide…