ABSTRACT
Introduction: The new SARS-CoV-2-mRNA-vaccines provide protection against severe COVID-19 infection. Disease modifying therapies (DMTs) for treatment of persons with multiple sclerosis (pwMS) differently impact humoral and cellular immunity and therefore can diminish vaccination outcomes. Thus, it is crucial to investigate the influence of different DMTs on the immune response after SARS-CoV-2 vaccination of pwMS. Objective(s): To investigate antibody and T-cell responses after SARS-CoV-2-vaccination in pwMS treated with different DMTs. Method(s): We studied antibody and T-cell responses in pwMS 4 and 12 weeks after the second dose of mRNA-vaccination against SARS-CoV-2. The results were compared to baseline samples taken before the first dose of SARS-CoV-2-vaccination. We screened and included 148 pwMS treatedwith natalizumab (n=23), dimethylfumarate (n=24), fingolimod (n=39), cladribine (n=31), alemtuzumab (n=17) and teriflunomide (n=14). Healthy controls (HC) (n=43) were used as a comparison. To evaluate humoral immune responses, IgG reactivity was measured towards three different SARS-CoV-2 antigens using a multiplex bead assay: full-length spike glycoprotein (spike S1S2 foldon), spike S1 domain and the nucleocapsid protein C-terminal domain (Nucleocapsid C). Furthermore, the antibody data allowed us to distinguish pwMS who had been vaccinated after a previous SARS-CoV-2-infection. Cellular immune responses were studied using a Fluorospot assay measuring IFNy and IL-13 T-cell responses to the spike S1 domain and Nucleocapsid C. Result(s): Humoral responses to vaccination were comparable between HC and pwMS treated with natalizumab, dimethylfumarate, cladribine, alemtuzumab and teriflunomide, but suppressed with fingolimod. In addition, T-cell responses were nearly absent in the fingolimod group and moderately reduced in the cladribine group. Conclusion(s): In this comprehensive study of both antibody and cellular responses to SARS-CoV-2-vaccination in pwMS on different DMTs, fingolimod was associated with abrogated responses in both aspects, while cladribine-treated individuals displayed reduced cellular response only. These findings are of relevance for risk mitigation strategies and vaccination recommendations for pwMS.