Strong T-cell activation in response to SARSCoV-2 vaccination in patients with multiple sclerosis on B-cell depleting therapies

ABSTRACT

Objective: 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. Background: 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 a reduction in circulating Bcells. 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. Design/Methods: We collected peripheral blood mononuclear cells (PBMCs) and serum samples from anti-CD20-treated MS patients and from 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-γ) release after protein-specific T-cell stimulation were measured ex vivo using an ELISpot assay. Results: We observed that out of 45 vaccinated anti-CD20-treated MS patients studied, 37 (82.2%) showed defective humoral immunity. Interestingly, most CoV2 spike IgG negative patients (35 out of 37, 94.6%) presented a T-cell response with positive expression of at least one cytokine. Conclusions: Our 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.