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

Vanessa J. Kirschner, Grant Feuer, Michaela Malin, Joyce Lei, Jiayuan Liu, Morgan Roche, Jerry Lin, Roberto Alfonso, Saud A. Sadiq Tisch Multiple Sclerosis Research Center of New York

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.

Abstract Date

November 8, 2021

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