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.

Autor:	Novak F; Department of Neurology, Hospital Southwest Jutland, University Hospital of Southern Denmark, Esbjerg, Denmark.; Department of Regional Health Research, University of Southern Denmark, Odense, Denmark., Nilsson AC; Clinical Immunology Research Unit, Department of Clinical Immunology, Odense University Hospital, Odense, Denmark.; Department of Clinical Research, University of Southern Denmark, Odense, Denmark., Christensen EB; Clinical Immunology Research Unit, Department of Clinical Immunology, Odense University Hospital, Odense, Denmark.; Department of Clinical Research, University of Southern Denmark, Odense, Denmark.; Centre for Cellular Immunotherapy of Haematological Cancer Odense (CITCO), Odense, Denmark., Stougaard CL; Clinical Immunology Research Unit, Department of Clinical Immunology, Odense University Hospital, Odense, Denmark.; Department of Clinical Research, University of Southern Denmark, Odense, Denmark.; Centre for Cellular Immunotherapy of Haematological Cancer Odense (CITCO), Odense, Denmark., Barnkob MB; Clinical Immunology Research Unit, Department of Clinical Immunology, Odense University Hospital, Odense, Denmark.; Department of Clinical Research, University of Southern Denmark, Odense, Denmark.; Centre for Cellular Immunotherapy of Haematological Cancer Odense (CITCO), Odense, Denmark., Holm DK; Clinical Immunology Research Unit, Department of Clinical Immunology, Odense University Hospital, Odense, Denmark., Witt AH; Department of Neurology, Hospitalsenhed Midt, Viborg, Denmark., Byg KE; Centre for Cellular Immunotherapy of Haematological Cancer Odense (CITCO), Odense, Denmark.; Department of Rheumatology, Odense University Hospital, Odense, Denmark., Johansen IS; Department of Clinical Research, University of Southern Denmark, Odense, Denmark.; Department of Infectious Diseases, Odense University Hospital, Odense, Denmark., Nielsen C; Clinical Immunology Research Unit, Department of Clinical Immunology, Odense University Hospital, Odense, Denmark.; Department of Clinical Research, University of Southern Denmark, Odense, Denmark.; Centre for Cellular Immunotherapy of Haematological Cancer Odense (CITCO), Odense, Denmark., Sejbaek T; Department of Neurology, Hospital Southwest Jutland, University Hospital of Southern Denmark, Esbjerg, Denmark.; Department of Regional Health Research, University of Southern Denmark, Odense, Denmark.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2024 Sep 05; Vol. 15, pp. 1432348. Date of Electronic Publication: 2024 Sep 05 (Print Publication: 2024).
DOI:	10.3389/fimmu.2024.1432348
Abstrakt:	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. Competing Interests: FN served on advisory boards for Sanofi and received travel grants from Sanofi and Merck. MB has receiving consulting honorariums from Roche and Kite/Gilead, unrelated to this work. TS has received travel grants from Biogen, Merck, Novartis, Roche, and Sanofi, has received research grants from Biogen, and has served on advisory boards for Biogen, Merck, Novartis, and Sanofi. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2024 Novak, Nilsson, Christensen, Stougaard, Barnkob, Holm, Witt, Byg, Johansen, Nielsen and Sejbaek.)
Databáze:	MEDLINE
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