Humoral and T-cell response to SARS-CoV-2 mRNA vaccine in multiple sclerosis patients: Correlations with DMTs and clinical variables

Disease-modifying therapies (DMTs) can affect vaccine responses in individuals with multiple sclerosis (MS). We assessed the humoral and T-cell responses following SARS-CoV-2 mRNA vaccination in MS patients receiving various DMTs. We prospectively enrolled 243 participants, including 113 healthy control subjects and 130 MS patients. Blood samples for detecting SARS-CoV-2 antibodies were collected at three time points: T0, before the first vaccine dose; T1, before the second dose; and T2, one month after the second dose. In a subgroup of 51 patients and 20 controls, samples were collected at T0 and T2 to assess the T-cell immune response to the Spike antigen of SARS-CoV-2 using ELISPOT-IFNγ. The IgG levels in patients treated with fingolimod and ocrelizumab (159.1 AU/ml and 467.1 AU/ml, respectively) were significantly lower than those in healthy controls and patients on other DMTs (P ​< ​0.0001). The mean Ig titers were higher in patients with an absolute lymphocyte count ≥1000 ​cells/mm3 compared to those with a count between 500 and 1000 and with a count <500 (mean ​± ​SD:7205.6 ​± ​7339.2, 2413.1 ​± ​4515.4 and 165.9 ​± ​152.2, respectively; p ​= ​0.008). We found correlations between antibody levels and age (r ​= ​0.233, p ​= ​0.008). A positive Spike-specific T-cell response was detectable in 100 ​% of vaccinated healthy controls and patients treated with teriflunomide, dimethyl-fumarate, and natalizumab, in 90.5 ​% of fingolimod patients, and in 63.8 ​% of ocrelizumab patients. There is a correlation between IgG-specific titer after SARS-CoV-2 vaccination and clinical variables (age, lymphocyte count). Notably, a T-cell-specific response to SARS-CoV-2 developed in patients treated with fingolimod and ocrelizumab, even with lower rates of humoral response.