Cutting Edge: Effect of Disease-Modifying Therapies on SARS-CoV-2 Vaccine-Induced Immune Responses in Multiple Sclerosis Patients.

Multiple sclerosis (MS) is a demyelinating inflamma-tory disease of the CNS treated by diverse disease-modifying therapies that suppress the immune sys-tem. Severe acute respiratory syndrome coronavirus 2 mRNA vaccines have been very effective in immuno-competent individuals, but whether MS patients treated with modifying therapies are afforded the same protection is not known. This study deter-mined that dimethyl fumarate caused a momentary reduction in anti-Spike (S)-specific Abs and CD8 T cell response. MS patients treated with B cell-deplet-ing (anti-CD20) or sphingosine 1-phosphate receptor agonist (fingolimod) therapies lack significant S-specific Ab response. Whereas S-specific CD4 and CD8 T cell responses were largely compromised by fingolimod treat-ment, T cell responses were robustly generated in anti-CD20-treated MS patients, but with a reduced propor-tion of CD4+CXCR5+ circulating follicular Th cells. These data provide novel information regarding vaccine immune response in patients with autoimmunity useful to help improve vaccine effectiveness in these populations. The Journal of Immunology, 2022, 208: 1519-1524.