2021 CMSC Annual Meeting

Temporal Trends in Humoral and Cellular Immune Responses to Sars-Cov-2 mRNA Vaccines Among Multiple Sclerosis Patients Treated with Natalizumab, Ocrelizumab or Fumarates

Background: Vaccines against SARS-CoV-2 are a key component of public health measures to combat the COVID-19 pandemic. The impact of immunomodulatory therapies on the efficacy of vaccines against SARS-CoV-2 is of considerable interest to MS patients and clinicians. Objectives: To examine the temporal trends of humoral and cell-mediated immune responses to SARS-CoV-2 mRNA vaccines among MS patients on different therapies. Methods: 22 MS patients treated with ocrelizumab (n=9), natalizumab (n=8), fumarates (n=5; diroximel fumarate, 3 and dimethyl fumarate, 2) received either BNT162b2 (Pfizer, n=15) or mRNA-1273 (Moderna, n=7) vaccines. Blood samples were collected prior to and 7 days after the first vaccine dose (T0 and T1), prior to and 7 days after the second vaccine dose (T2 and T3), and 2 months after 2nd vaccine dose (T4). Anti-SARS-CoV-2 spike protein IgG titers were measured using quantitative ECLIA assay (Cov2Quant, Labcorp). T-cell reactivity was determined by measuring interferon-gamma and interleukin-2 production in response to stimulation with protein fragments of SARS-CoV-2, using ELISPOT. Results: All of the patients in natalizumab and fumarate cohorts, but only 22% (2/9) of ocrelizumab cohort developed detectable levels of anti-SARS-CoV-2 antibodies. The antibody response developed earliest in the fumarate cohort, at T2 timepoint (3-4 weeks after the first vaccine dose). The highest antibody titers were measured 10 days after the second vaccine dose, without significant difference between the natalizumab and fumarate cohorts. Two months after the second vaccine dose, the antibody titers decreased by 72% in natalizumab-treated cohort, and by 44% in fumarate-treated cohort. T-cell reactivity was observed in all cohorts, was detectable as early as 7 days after the first vaccination (T1), and was further increased following the second vaccination (T3). Conclusions: Natalizumab- and fumarate-treated MS patients mounted robust antibody response to SARS-CoV-2 mRNA vaccines, in contrast to ocrelizumab-treated patients. T-cell responses were comparable among all three treatment cohorts. Antibody titers decreased by 44-72% two months after the second vaccine dose.