ABSTRACT
Introduction: The generation of humoral and cellular responses by SARS-CoV2 vaccination in patients with multiple sclerosis (pwMS) especially onsphingosin-1-phosphat receptor (S1PR) modulator treatment is not yet understood. In this study we aim to differentiate the immunological response profiles after 2 mRNA SARS-CoV2 vaccinations depending on timing and unselective vs. selective S1PR modulators in pwMS. Method(s): We conducted a cross-sectional study among pwMS on ozanimod (OZA), fingolimod (FTY) or without disease-modifying treatment. Two courses of mRNA SARS-CoV-2 vaccinations were performed on treatment resp. before treatment start. Demographic data on age, sex and disease progression did no significantly differ in selected groups. Blood was analyzed for SARS-CoV-2 spike protein-specific antibodies and for CD4 and CD8 T cell response by interferon-gamma release assay upon stimulation. Result(s): All untreated pwMS (n=31) developed positive antibodies (930.9 +/-803.7 BAU/mL), but only in 50% positive T cell responses were seen (S1 0.39 +/-0.68;S2 0.43 +/-0.67 IU/mL). PwMS on longterm FTY treatment (n=86) showed B cell responses (45.0 +/-117.9 BAU/mL) only in 27,9% and T cell responses (S1 0.11 +/-0.86;S2 0.01 +/-0.05 IU/mL) only in 5,9% both with significant lower titers compared to untreated pwMS. In contrast, pwMS on OZA (n= 22) developed B cell responses in 84.2% of patients (703.8 +/-837.5 BAU/mL) with lower titers than untreated pwMS. T cell responses were present in only 4,5% of patients on OZA (S1 0.02 +/-0.05;S2 0.03 +/-0.09 IU/mL). When patients were vaccinated before OZA start (n=25) and tested later on OZA treatment, all patients presented with positive antibody titers comparable to untreated patients (1466.2 +/-838.8 BAU/mL). However, T cell responses could be detected only in 19,0% of these OZA patients (S1 0.05 +/-0.11;S2 0.06 +/-0.14 IU/mL). In summary, only 15.8% OZA, but 69,8% FTY patients did neither develop B nor T cell response. In contrast untreated patients as well as vaccinated patients before OZA treatment start present with at least one B or T cell response. Conclusion(s): In this study, we present that B and T cell responses to SARS-CoV2 mRNA vaccines are selectively affected by different S1PR modulators. Vaccination before start of S1PR modulation induced a stable B cell response which could be demonstrated on treatment. These findings should be considered for vaccination strategies during S1PR modulatory therapy.