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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Multiple Sclerosis and Neuroimmunology
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1432348

Humoral and cellular immune response from first to fourth SARS-CoV-2 mRNA vaccination in anti-CD20-treated multiple sclerosis patients -A longitudinal cohort study

Provisionally accepted
Frederik Novak Frederik Novak 1,2*Anna C. Nilsson Anna C. Nilsson 3,4Emil Birch Christensen Emil Birch Christensen 3,4,5Caroline L. Stougaard Caroline L. Stougaard 3,4,5Mike B. Barnkob Mike B. Barnkob 3,4,5Dorte K. Holm Dorte K. Holm 3Agnes H. Witt Agnes H. Witt 6Keld-Erik Byg Keld-Erik Byg 7Isik S. Johansen Isik S. Johansen 8Christian Nielsen Christian Nielsen 3,4,5Tobias Sejbaek Tobias Sejbaek 1,2
  • 1 Department of Neurology, Esbjerg Hospital, University Hospital Southern Denmark, Esbjerg, Denmark
  • 2 Department of Regional Health Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark
  • 3 Research unit of Clinical Immunology, Department of Clinical Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark
  • 4 Department of Clinical Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark
  • 5 Other, Odense, Denmark
  • 6 Hospitalsenhed Midt, Other, Viborg, Denmark
  • 7 Department of Rheumatology, Odense University Hospital, Odense, Denmark
  • 8 Department of Infetious Diseases, Odense University Hospital, Odense, Denmark

The final, formatted version of the article will be published soon.

    Background This study examines the humoral and cellular response in multiple sclerosis (MS) patients on anti-CD20 therapy before and after the 1st to 4th BNT162b2 mRNA SARS-CoV-2 vaccination and the relationship with breakthrough infection. Methods Participants with McDonald 2017 MS that were treated with ocrelizumab were included. The study duration was throughout the COVID-19 pandemic until four months after fourth mRNA SARS-CoV-2 vaccination (BNT162b2). Longitudinal blood samples were analysed for: IgG antibodies of SARS-CoV-2 spike anti-receptor binding domain (anti-RBD), nucleocapsid IgG antibodies (anti-N) and activation induced marker expressing CD4+, CD8+ T-cells and concentration of ocrelizumab and anti-drug antibodies. Incidences of breakthrough infection were confirmed with SARS-CoV-2 PCR tests. Results The rate of anti-RBD positive participants increased substantially between the third and fourth vaccination from 22.2% to 55.9% (median 54.7 BAU/mL; IQR: 14.5 – 221.2 BAU/mL and 607.7 BAU/mL; IQR: 29.4 – 784.6 BAU/mL, respectively). Within the same period 75% of participants experienced breakthrough infection. The fourth vaccination resulted in an additional increase in seropositive individuals (64.3%) (median 541.8 BAU/mL (IQR: 19.1-1007 BAU/mL). Breakthrough infection did not influence the cellular response without a significant change after the fourth vaccination. During the study period two participants had detectable anti-N, both after the fourth vaccination. No correlation was found between serum concentration of ocrelizumab and the humoral and cellular response. Discussion Low levels or absence of specific anti-RBD following vaccination, with a significant increase after breakthrough infections and boosted by the fourth vaccination. T-cell reactivity remained sustained and unaffected by breakthrough infections.

    Keywords: Multiple Sclerosis, Anti-CD20, mRNA vaccination vulnerable population, SARS-CoV-2, Ocrelizumab concentration, Breakthrough infection, Humoral immune response , Cellular immune activation

    Received: 13 May 2024; Accepted: 09 Aug 2024.

    Copyright: © 2024 Novak, Nilsson, Birch Christensen, Stougaard, Barnkob, Holm, Witt, Byg, Johansen, Nielsen and Sejbaek. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Frederik Novak, Department of Neurology, Esbjerg Hospital, University Hospital Southern Denmark, Esbjerg, Denmark

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.