T-cell activation in patients with multiple sclerosis on B-cell depleting therapies is as effective as that of general population in response to SARS-CoV-2 vaccination

Many patients with multiple sclerosis (MS) undergo immunosuppressive B-cell depleting therapies which can severely limit their humoral immunity against SARS-CoV-2 (CoV2) infection or response to vaccination. While robust antibody production is seen in immunocompetent individuals, recent studies show that B-cell depleting therapies inhibit efficient production of antibodies against CoV2 proteins due to reduction in circulating B-cells. It is unknown how these disease modifying therapies affect T-cell responses after CoV2 vaccination, and whether there is a correlation between CoV2 antibody levels and T-cell immunity.

Our ongoing single-center study aims to determine CoV2 spike protein-T-cell reactivity in fully vaccinated, B-cell depleted MS patients treated with rituximab or ocrelizumab, two well-characterized anti-CD20 monoclonal antibody drugs. We collected peripheral blood mononuclear cells (PBMCs) and serum samples from treated MS patients and healthy control individuals at 15-93 days after completing vaccination. CoV2 IgG response was determined using anti-spike protein-based serology and levels of proinflammatory cytokine (IL-2 and INF-Ɣ)release after protein-specific T-cell stimulation were measured ex vivo using an ELISpot assay.

We observe that from 23 vaccinated MS anti-CD20 treated patients studied, 19 (82.6%) showed defective humoral immunity. Interestingly, most CoV2 spike IgG negative patients (17 out of 19, 89.5%) presented a positive T cell response with strong IL-2 and INF-Ɣ expression.These results suggest the generation of a partial adaptive immune response to CoV2 vaccination in B-cell depleted individuals, driven by a functionally competent T-cell arm. Investigation into the role of T-cell response in these individuals is crucial to identifying their levels of protection against COVID-19.