Department of Immunopathology, Sanquin Research and Landsteiner Laboratory, University of Amsterdam, Amsterdam, Netherlands
Ruth R Hagen
Department of Hematopoiesis, Sanquin Research and Landsteiner Laboratory, University of Amsterdam, Amsterdam, Netherlands; Department of Experimental Immunohematology, Sanquin Research and Landsteiner Laboratory, Amsterdam, Netherlands
Department of Hematopoiesis, Sanquin Research and Landsteiner Laboratory, University of Amsterdam, Amsterdam, Netherlands; Department of Experimental Immunohematology, Sanquin Research and Landsteiner Laboratory, Amsterdam, Netherlands
Sydney Cytometry Core Research Facility, Charles Perkins Centre, Centenary Institute, and The University of Sydney, Sydney, Australia; School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Sydney, Australia
Laura YL Kummer
Department of Neurology and Neurophysiology, Amsterdam Neuroscience, University of Amsterdam, Amsterdam, Netherlands
Maurice Steenhuis
Department of Immunopathology, Sanquin Research and Landsteiner Laboratory, University of Amsterdam, Amsterdam, Netherlands
Mariel Duurland
Department of Immunopathology, Sanquin Research and Landsteiner Laboratory, University of Amsterdam, Amsterdam, Netherlands
Rivka de Jongh
Department of Immunopathology, Sanquin Research and Landsteiner Laboratory, University of Amsterdam, Amsterdam, Netherlands
Nina de Jong
Department of Immunopathology, Sanquin Research and Landsteiner Laboratory, University of Amsterdam, Amsterdam, Netherlands
C Ellen van der Schoot
Department of Experimental Immunohematology, Sanquin Research and Landsteiner Laboratory, Amsterdam, Netherlands
Amélie V Bos
Department of Immunopathology, Sanquin Research and Landsteiner Laboratory, University of Amsterdam, Amsterdam, Netherlands
Erik Mul
Department of Research Facilities, Sanquin Research, Amsterdam, Netherlands
Department of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia; Global Station for Zoonosis Control, Global Institution for Collaborative Research and Education (GI-CoRE), Hokkaido University, Sapporo, Japan
Koos PJ van Dam
Department of Neurology and Neurophysiology, Amsterdam Neuroscience, University of Amsterdam, Amsterdam, Netherlands
Eileen W Stalman
Department of Neurology and Neurophysiology, Amsterdam Neuroscience, University of Amsterdam, Amsterdam, Netherlands
Laura Boekel
Department of Rheumatology, Amsterdam Rheumatology and immunology Center, Amsterdam, Netherlands
Gertjan Wolbink
Department of Immunopathology, Sanquin Research and Landsteiner Laboratory, University of Amsterdam, Amsterdam, Netherlands; Department of Rheumatology, Amsterdam Rheumatology and immunology Center, Amsterdam, Netherlands
Sander W Tas
Amsterdam Rheumatology and immunology Center, Department of Rheumatology and Clinical Immunology, University of Amsterdam, Amsterdam, Netherlands
Joep Killestein
Amsterdam UMC, Vrije Universiteit, Department of Neurology, Amsterdam, Netherlands
Zoé LE van Kempen
Amsterdam UMC, Vrije Universiteit, Department of Neurology, Amsterdam, Netherlands
Department of Neurology and Neurophysiology, Amsterdam Neuroscience, University of Amsterdam, Amsterdam, Netherlands; Department of Clinical Neurophysiology, St Antonius Hospital, Nieuwegein, Netherlands
Taco W Kuijpers
Department of Pediatric Immunology, Rheumatology and Infectious Disease, University of Amsterdam, Amsterdam, Netherlands
Filip Eftimov
Department of Neurology and Neurophysiology, Amsterdam Neuroscience, University of Amsterdam, Amsterdam, Netherlands
Theo Rispens
Department of Immunopathology, Sanquin Research and Landsteiner Laboratory, University of Amsterdam, Amsterdam, Netherlands
S Marieke van Ham
Department of Immunopathology, Sanquin Research and Landsteiner Laboratory, University of Amsterdam, Amsterdam, Netherlands; Swammerdam Institute for Life Sciences, University of Amsterdam, Amsterdam, Netherlands
Anja ten Brinke
Department of Immunopathology, Sanquin Research and Landsteiner Laboratory, University of Amsterdam, Amsterdam, Netherlands
Department of Hematopoiesis, Sanquin Research and Landsteiner Laboratory, University of Amsterdam, Amsterdam, Netherlands; Department of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia
On behalf of the T2B! immunity against SARS-CoV-2 study group
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 severe acute respiratory syndrome coronavirus 2 (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 (HCs) 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 HCs 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. Conclusions: Together, these findings indicate that SARS-CoV-2 experienced MS-OCR patients may still benefit from vaccination by inducing a broad CD8+ T cell response which has been associated with milder disease outcome. The delayed vaccine-induced IgG kinetics in RA-MTX patients indicate an increased risk after the first vaccination, which might require additional shielding or alternative strategies such as treatment interruptions in vulnerable 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).
