Meyer-Arndt, Lil ORCID: 0000-0002-7909-020X, Braun, Julian, Fauchere, Florent ORCID: 0000-0002-1955-6362, Vanshylla, Kanika ORCID: 0000-0003-4552-9170, Loyal, Lucie ORCID: 0000-0001-5738-4437, Henze, Larissa, Kruse, Beate, Dingeldey, Manuela, Juerchott, Karsten, Mangold, Maike, Maraj, Ardit, Braginets, Andre, Boettcher, Chotima, Nitsche, Andreas, de la Rosa, Kathrin ORCID: 0000-0003-4809-3157, Ratswohl, Christoph ORCID: 0000-0001-5413-0730, Sawitzki, Birgit ORCID: 0000-0001-8166-8579, Holenya, Pavlo, Reimer, Ulf, Sander, Leif E., Klein, Florian ORCID: 0000-0003-1376-1792, Paul, Friedemann, Bellmann-Strobl, Judith, Thiel, Andreas ORCID: 0000-0002-5515-4002 and Giesecke-Thiel, Claudia ORCID: 0000-0002-5927-7018 (2022). SARS-CoV-2 mRNA vaccinations fail to elicit humoral and cellular immune responses in patients with multiple sclerosis receiving fingolimod. J. Neurol. Neurosurg. Psychiatry, 93 (9). S. 960 - 972. LONDON: BMJ PUBLISHING GROUP. ISSN 1468-330X

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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-beta, 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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Meyer-Arndt, LilUNSPECIFIEDorcid.org/0000-0002-7909-020XUNSPECIFIED
Braun, JulianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fauchere, FlorentUNSPECIFIEDorcid.org/0000-0002-1955-6362UNSPECIFIED
Vanshylla, KanikaUNSPECIFIEDorcid.org/0000-0003-4552-9170UNSPECIFIED
Loyal, LucieUNSPECIFIEDorcid.org/0000-0001-5738-4437UNSPECIFIED
Henze, LarissaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kruse, BeateUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dingeldey, ManuelaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Juerchott, KarstenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mangold, MaikeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Maraj, ArditUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Braginets, AndreUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Boettcher, ChotimaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nitsche, AndreasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
de la Rosa, KathrinUNSPECIFIEDorcid.org/0000-0003-4809-3157UNSPECIFIED
Ratswohl, ChristophUNSPECIFIEDorcid.org/0000-0001-5413-0730UNSPECIFIED
Sawitzki, BirgitUNSPECIFIEDorcid.org/0000-0001-8166-8579UNSPECIFIED
Holenya, PavloUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Reimer, UlfUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sander, Leif E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Klein, FlorianUNSPECIFIEDorcid.org/0000-0003-1376-1792UNSPECIFIED
Paul, FriedemannUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bellmann-Strobl, JudithUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Thiel, AndreasUNSPECIFIEDorcid.org/0000-0002-5515-4002UNSPECIFIED
Giesecke-Thiel, ClaudiaUNSPECIFIEDorcid.org/0000-0002-5927-7018UNSPECIFIED
URN: urn:nbn:de:hbz:38-693369
DOI: 10.1136/jnnp-2022-329395
Journal or Publication Title: J. Neurol. Neurosurg. Psychiatry
Volume: 93
Number: 9
Page Range: S. 960 - 972
Date: 2022
Publisher: BMJ PUBLISHING GROUP
Place of Publication: LONDON
ISSN: 1468-330X
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
ANTIBODY-RESPONSE; INFLUENZA VACCINE; INFECTION; EFFECTORMultiple languages
Clinical Neurology; Psychiatry; SurgeryMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/69336

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