• Niels J M Verstegen, Ruth R Hagen, Christine Kreher, Lisan H Kuijper, Jet van den Dijssel, Thomas Ashhurst, Laura Y L Kummer, Virginia Palomares Cabeza, Maurice Steenhuis, Mariël C Duurland, Rivka de Jongh, SchootC Ellen van derCEVDepartment of Experimental Immunohematology, Sanquin Research and Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands., Veronique A L Konijn, Erik Mul, Katherine Kedzierska, Koos P J van Dam, Eileen W Stalman, Laura Boekel, Gertjan Wolbink, Sander W Tas, Joep Killestein, Theo Rispens, Luuk Wieske, Taco W Kuijpers, Filip Eftimov, Zoé L E van Kempen, van HamS MariekeSMDepartment of Immunopathology, Sanquin Research and Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.Swammerdam Institute for Life Sciences, University of Amsterdam, Amsterdam, The Netherlands., Anja Ten Brinke, Carolien E van de Sandt, and T2B! immunity against SARS-CoV-2 study group.
• Department of Immunopathology, Sanquin Research and Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
• J. Neurol. Neurosurg. Psychiatr. 2024 Mar 28.

BackgroundMessenger RNA (mRNA) vaccines provide robust protection against SARS-CoV-2 in healthy individuals. However, immunity after vaccination of patients with multiple sclerosis (MS) treated with ocrelizumab (OCR), a B cell-depleting anti-CD20 monoclonal antibody, is not yet fully understood.MethodsIn this study, deep immune profiling techniques were employed to investigate the immune response induced by SARS-CoV-2 mRNA vaccines in untreated patients with MS (n=21), OCR-treated patients with MS (n=57) and healthy individuals (n=30).ResultsAmong OCR-treated patients with MS, 63% did not produce detectable levels of antibodies (non-seroconverted), and those who did have lower spike receptor-binding domain-specific IgG responses compared with healthy individuals and untreated patients with MS. Before vaccination, no discernible immunological differences were observed between non-seroconverted and seroconverted OCR-treated patients with MS. However, non-seroconverted patients received overall more OCR infusions, had shorter intervals since their last OCR infusion and displayed higher OCR serum concentrations at the time of their initial vaccination. Following two vaccinations, non-seroconverted patients displayed smaller B cell compartments but instead exhibited more robust activation of general CD4+ and CD8+ T cell compartments, as indicated by upregulation of CD38 and HLA-DR surface expression, when compared with seroconverted patients.ConclusionThese findings highlight the importance of optimising treatment regimens when scheduling SARS-CoV-2 vaccination for OCR-treated patients with MS to maximise their humoral and cellular immune responses. This study provides valuable insights for optimising vaccination strategies in OCR-treated patients with MS, including the identification of CD38 and HLA-DR as potential markers to explore vaccine efficacy in non-seroconverting OCR-treated patients with MS.© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.

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