Multiple sclerosis patients under treatment with interferon β1-a or ocrelizumab exhibit different T and B cell responses to SARS-CoV-2 vaccine

Introduction: Multiple sclerosis (MS) is a long-term autoimmune disease characterized by inflammation and progressive degeneration of the central nervous system. Disease-modifying therapies (DMTs) have proved to be effective at ameliorating the course of MS. DMTs are immunomodulatory drugs affecting immune response to SARS-CoV-2 and its vaccine efficacy in MS patients (pwMS). Methods: In this longitudinal study, we analyzed T and B cell subsets in peripheral blood and the antigen (spike)-specific T cell response in pwMS patients undergoing interferon β1-a (IFN) or ocrelizumab (OCRE), before and after BNT162b2 mRNA SARS-CoV-2 vaccination. Blood was collected from pwMS treated with IFN and OCRE before and after the two vaccine doses. Peripheral blood mononuclear cells were analyzed by flow cytometry to measure T and B cell frequency, the expression of activation/regulatory/memory T cell markers and their spike-specific T cell response. Results: CD20+ B-cells were decreased in OCRE- compared to IFN- treated pwMS before and after vaccination. CD8+ and CD4+ T cell responses and the immunological memory was comparable between the two groups. Th17 cells were increased after vaccination only in the OCRE-treated group. We detected a robust spike-specific T cell response, paralleled by a significant decrease of Treg frequency, in both pwMS groups. Discussion: Although IFN and OCRE induced distinct immunological profile, both DMTs allowed to mount a vaccine-induced cellular and humoral immune response. This study also represents a model that could be applied to dissect the vaccine-elicited immune response in individuals undergoing treatment with different biological drugs.