To investigate the humoral and T-cell immune response of multiple sclerosis (MS) patients under B-cell depleting therapy following SARS-CoV-2 vaccination compared to healthy controls (HC).

The SARS-CoV-2 pandemic has huge implications for the management of patients with MS under highly active immune therapies. First reports indicated that the humoral response of anti-CD20 treated, B-cell depleted patients might by attenuated. Data about dynamics of B-cell repopulation and T-cell response are scarce. 

The study was authorized by the local ethics committee of the Ruhr-University Bochum. Patients were recruited at the Department of Neurology. We included n=10 healthy age-matched controls and n=37 B-cell depleted MS patients (20 ocrelizumab, 17 off-label rituximab). Serum and Peripheral Blood Mononuclear Cells (PBMCs) were isolated 4-8 weeks after second vaccination. Serum was analyzed for anti-SARS-CoV-2-Spike antibodies. Lymphocyte subpopulations were analyzed in B-cell depleted patients by FACS analysis. PBMCs were stimulated with 2 µg/ml SARS-CoV-2 peptide-mix for 16-18 hours and analyzed via flow cytometry for cytokine-expressing T-cell populations.

15/36 (40.5%) patients mounted an antibody response >10 U/ml (range 0.8-2,500). The anti-SARS-CoV-2-Spike titer correlated with B-cell repopulation (R²=0.01841; r=0.4481; p=0.0069), whereas no significance could be detected correlating with the time to last infusion (R^²=0.1352; r=0.3058; p=0.0740). On the contrary, T-cell responses of B-cell depleted patients were higher or did not deviate from those of HC. Frequencies of CD4⁺-T-cells expressing IFN-γ or IL-4 and CD8⁺-T-cells expressing IFN-γ or IFN-γ and IL-2 were significantly higher in B-cell depleted patients, while CD4⁺-T-cells expressing IL-2 or IFN-γ and IL-2 as well as CD8⁺-T-cells expressing IL-2 did not differ from HC.

Humoral vaccination responses in B-cell depleted patients are dependent on B-cell repopulation. Notably, patients with poor humoral response are able to mount a sustained T-cell response after SARS-CoV-2 vaccination. Those data suggest, that vaccinated B-cell depleted patients might be partially protected against SARS-CoV-2 infection.