SARS-CoV-2 Vaccination Responses in Anti-CD20-Treated Progressive Multiple Sclerosis Patients Show Immunosenescence in Antigen-Specific B and T Cells.

Clinical, pathological, and imaging evidence in multiple sclerosis (MS) shows that inflammation starts early and progresses with age. B cells play a central role in this process, contributing to cytokine production, defective regulatory functions, and abnormal immunoglobulin production, even in the central nervous system. Anti-CD20 (aCD20) therapies, which deplete CD20 B cells, are largely used in the treatment of both relapsing remitting (RR) and progressive (PR) forms of MS. Although effective against MS symptoms and lesions detectable by magnetic resonance imaging, aCD20 therapies can reduce the immune response to COVID-19 vaccination. By using high-parameter flow cytometry, we examined the antigen-specific (Ag) immune response six months post-third COVID-19 mRNA vaccination in MS patients with RR and PR forms on aCD20 therapy. Despite lower Ag B cell responses and lower levels of anti-SARS-CoV2, both total and neutralizing antibodies, RR and PR patients developed strong Ag T cell responses. We observed similar percentages and numbers of Ag CD4 T cells and a high proportion of Ag CD8 T cells, with slight differences in T cell phenotype and functionality; this, however, suggested the presence of differences in immune responses driven by age and disease severity.