TY - JOUR TI - Immune dynamics in SARS-CoV-2 experienced immunosuppressed rheumatoid arthritis or multiple sclerosis patients vaccinated with mRNA-1273 AU - Verstegen, Niels JM AU - Hagen, Ruth R AU - van den Dijssel, Jet AU - Kuijper, Lisan H AU - Kreher, Christine AU - Ashhurst, Thomas AU - Kummer, Laura YL AU - Steenhuis, Maurice AU - Duurland, Mariel AU - de Jongh, Rivka AU - de Jong, Nina AU - van der Schoot, C Ellen AU - Bos, Amélie V AU - Mul, Erik AU - Kedzierska, Katherine AU - van Dam, Koos PJ AU - Stalman, Eileen W AU - Boekel, Laura AU - Wolbink, Gertjan AU - Tas, Sander W AU - Killestein, Joep AU - van Kempen, Zoé LE AU - Wieske, Luuk AU - Kuijpers, Taco W AU - Eftimov, Filip AU - Rispens, Theo AU - van Ham, S Marieke AU - ten Brinke, Anja AU - van de Sandt, Carolien E A2 - Sasson, Sarah A2 - Davenport, Miles P A2 - Sasson, Sarah VL - 11 PY - 2022 DA - 2022/07/15 SP - e77969 C1 - eLife 2022;11:e77969 DO - 10.7554/eLife.77969 UR - https://doi.org/10.7554/eLife.77969 AB - 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). KW - autoimmune disease KW - SARS-CoV-2 KW - immunosuppressant KW - rheumatoid arthritis KW - multiple sclerosis KW - COVID-19 mRNA vaccine KW - immunity JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -