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. 2023 Jan;94(1):19-22.
doi: 10.1136/jnnp-2021-327612. Epub 2021 Oct 20.

Humoral immunity to SARS-CoV-2 mRNA vaccination in multiple sclerosis: the relevance of time since last rituximab infusion and first experience from sporadic revaccinations

Marton König  1 , Åslaug Rudjord Lorentzen  2   3 , Hilde Marie Torgauten  4   5 , The Trung Tran  6 , Stine Schikora-Rustad  2 , Eline Benno Vaage  6 , Åse Mygland  2   5 , Stig Wergeland  7   8 , Jan Aarseth  7   8 , Ingeborg Aase S Aaberge  9 , Øivind Torkildsen  5   7 , Trygve Holmøy  10   11 , Tone Berge  12   13 , Kjell-Morten Myhr  4   5 , Hanne Flinstad Harbo  14   11 , Jan Terje Andersen  11   15 , Ludvig Andre Munthe  6   16 , Arne Søraas  17 , Elisabeth Gulowsen Celius  14   11 , John Torgils Vaage  6 , Fridtjof Lund-Johansen  6 , Gro Owren Nygaard  14
Affiliations

Humoral immunity to SARS-CoV-2 mRNA vaccination in multiple sclerosis: the relevance of time since last rituximab infusion and first experience from sporadic revaccinations

Marton König et al. J Neurol Neurosurg Psychiatry. 2023 Jan.

Abstract

Introduction: The effect of disease-modifying therapies (DMT) on vaccine responses is largely unknown. Understanding the development of protective immunity is of paramount importance to fight the COVID-19 pandemic.

Objective: To characterise humoral immunity after mRNA-COVID-19 vaccination of people with multiple sclerosis (pwMS).

Methods: All pwMS in Norway fully vaccinated against SARS-CoV-2 were invited to a national screening study. Humoral immunity was assessed by measuring anti-SARS-CoV-2 SPIKE RBD IgG response 3-12 weeks after full vaccination, and compared with healthy subjects.

Results: 528 pwMS and 627 healthy subjects were included. Reduced humoral immunity (anti-SARS-CoV-2 IgG <70 arbitrary units) was present in 82% and 80% of all pwMS treated with fingolimod and rituximab, respectively, while patients treated with other DMT showed similar rates as healthy subjects and untreated pwMS. We found a significant correlation between time since the last rituximab dose and the development of humoral immunity. Revaccination in two seronegative patients induced a weak antibody response.

Conclusions: Patients treated with fingolimod or rituximab should be informed about the risk of reduced humoral immunity and vaccinations should be timed carefully in rituximab patients. Our results identify the need for studies regarding the durability of vaccine responses, the role of cellular immunity and revaccinations.

Keywords: COVID-19; immunology; multiple sclerosis.

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Conflict of interest statement

Competing interests: ARL research fundings from Sanofi. SW has received speaker honoraria from and served on scientific advisory boards for Biogen, Janssen-Cilag, Sanofi and Novartis. ØT has received speaker honoraria from and served on scientific advisory boards for Biogen, BMS, Jansen, Sanofi, Merck and Novartis. TH has received speaker honoraria and/or unrestricted research grants from Biogen, Merck, Roche, Novartis, Sanofi and Bristol-Myers Squibb, and participated in clinical trials organised by Merck, Sanofi and Roche. TB has received unrestricted research grants from Biogen Idec and Sanofi Genzyme. MK-M has received unrestricted research grants to his institution; scientific advisory board and speaker honoraria from Biogen, Merck, Novartis, Roche and Sanofi, and has participated in clinical trials organised by Biogen, Merck, Novartis, Roche and Sanofi. HFH has received honoraria for lecturing or advice from Biogen, Merck, Roche, Novartis and Sanofi. AS is shareholder of Age Labs, a molecular diagnostics company that discovers, develops and commercialises diagnostic tests for the early detection of age-related diseases. EGC has received honoraria for lecturing and advice from Biogen, BMS, Janssen, Merck, Novartis, Roche and Sanofi.

Figures

Figure 1
Figure 1
(A) COVID-19 vaccine response in healthy individuals and people with MS. The dot plots show levels of antibodies to SARS-CoV-2 Spike Protein (y-axis) and the receptor-binding domain (RBD) for indicated cohort. The dashed red lines correspond to assay cut-off determined for sero-prevalence screening (5 anti-SARS-CoV-2 SPIKE RBD IgG arbitrary units), while the rectangle shows the range of signals measured for more than >99% of vaccinated healthy individuals (<70 anti-SARS-CoV-2 SPIKE RBD IgG arbitrary units). The lower end corresponds to approximately 40 WHO binding antibody units (BAUs). (B) Scatter plot showing the correlation between time since last rituximab infusion and anti-SARS-CoV-2 SPIKE RBD IgG levels (AU). The red reference line on the Y-axis is positioned at 70 AU. (C) Scatter plot showing the correlation between CD19+ B-lymphocyte count (cells/mm3) prior to first vaccine dose and anti-SARS-CoV-2 SPIKE RBD IgG levels (AU, n=47, median of 2 months between CD19+ B-lymphocyte count and first vaccine dose). The red reference line on the Y axis is positioned at 70 AU. (D) Cox proportional-hazard model showing the cumulative probability of mounting a normal immune response (anti-SARS-CoV-2 SPIKE RBD IgG >70 AU) in relation to time since last rituximab infusion.
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