Immune dynamics in SARS-CoV-2 experienced immunosuppressed rheumatoid arthritis or multiple sclerosis patients vaccinated with mRNA-1273
- Sanquin, Netherlands
- University of Sydney, Australia
- Amsterdam University Medical Centers, Netherlands
- University of Melbourne, Australia
- Reade, Netherlands
Abstract
Background: Patients affected by different types of autoimmune diseases, including common conditions such as Multiple Sclerosis (MS) and Rheumatoid Arthritis (RA), are often treated with immunosuppressants to suppress disease activity. It is not fully understood how the SARS-CoV-2 specific humoral and cellular immunity induced by infection and/or upon vaccination is affected by immunosuppressants.
Methods: The dynamics of cellular immune reactivation upon vaccination of SARS-CoV-2 experienced MS patients treated with the humanized anti-CD20 monoclonal antibody ocrelizumab (OCR) and RA patients treated with methotrexate (MTX) monotherapy were analyzed at great depth via high-dimensional flow cytometry of whole blood samples upon vaccination with the SARS-CoV-2 mRNA-1273 (Moderna) vaccine. Longitudinal B and T cell immune responses were compared to SARS-CoV-2 experienced healthy controls (HC) before and 7-days after the first and second vaccination.
Results: OCR-treated MS patients exhibit a preserved recall response of CD8+ T central memory cells following first vaccination compared to healthy controls and a similar CD4+ circulating T follicular helper 1 and T helper 1 dynamics, whereas humoral and B cell responses were strongly impaired resulting in absence of SARS-CoV-2 specific humoral immunity. MTX treatment significantly delayed antibody levels and B reactivation following the first vaccination, including sustained inhibition of overall reactivation marker dynamics of the responding CD4+ and CD8+ T cells.
Conclusion: Together, these findings indicate that SARS-CoV-2 experienced MS-OCR patients still benefit from vaccination by inducing a broad CD8+ T cell response which can contribute to milder disease outcome. A delayed dynamics of vaccine-induced immunological recall in RA-MTX patients support repeated vaccine strategies to protect against future variants of concern, especially for these patients.
Funding: This research project was supported by ZonMw (The Netherlands Organization for Health Research and Development, #10430072010007), the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement (#792532 and #860003), the European Commission (SUPPORT-E, #101015756) and by PPOC (#20_21 L2506), the NHMRC Leadership Investigator Grant (#1173871).
Data availability
All raw and processed data presented in this study are available at https://flowrepository.org/id/FR-FCM-Z52K
Article and author information
Author details
Niels JM Verstegen
Jet van den Dijssel
Katherine Kedzierska
Carolien E van de Sandt
Funding
ZonMw (#10430072010007)
- Taco W Kuijpers
- Filip Eftimov
- Theo Rispens
Horizon 2020 Framework Programme (#860003)
- Taco W Kuijpers
- Filip Eftimov
- Theo Rispens
- Carolien E van de Sandt
European Commission (#101015756)
- Niels JM Verstegen
Horizon 2020 Framework Programme (#792532)
- Carolien E van de Sandt
NHMRC (1173871)
- Joep Killestein
PPOC (#20_21 L2506)
- Taco W Kuijpers
- Filip Eftimov
- Theo Rispens
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Sarah Sasson, The Kirby Institute UNSW, Australia
Ethics
Human subjects: This study was approved by the medical ethical committee (NL74974.018.20 and EudraCT 2021-001102-30, local METC nummer: 2020_194) and registered at Dutch Trial Register (Trial ID NL8900). Written informed consent was obtained from all study participants when enrolled. Participants were recruited between April 16th 2021 and May 20th 2021 at the MS Center Amsterdam, Amsterdam UMC and the Amsterdam READE Rheumatology and Immunology Center and vaccinated between April 19th 2021 and July 1st 2021 with the mRNA-1273 (Moderna) vaccine at an interval of six weeks, according to the Dutch national vaccination guidelines.
Version history
- Received: February 17, 2022
- Accepted: July 14, 2022
- Accepted Manuscript published: July 15, 2022 (version 1)
- Version of Record published: July 29, 2022 (version 2)
Copyright
© 2022, Verstegen et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Immune dynamics in SARS-CoV-2 experienced immunosuppressed rheumatoid arthritis or multiple sclerosis patients vaccinated with mRNA-1273
eLife 11:e77969.
https://doi.org/10.7554/eLife.77969
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