Abstract
BACKGROUNDVaccine-elicited adaptive immunity is a prerequisite for control of SARS-CoV-2 infection. Multiple sclerosis (MS) disease-modifying therapies (DMTs) differentially target humoral and cellular immunity. A comprehensive comparison of the effects of MS DMTs on SARS-CoV-2 vaccine–specific immunity is needed, including quantitative and functional B and T cell responses.METHODSSpike-specific Ab and T cell responses were measured before and following SARS-CoV-2 vaccination in a cohort of 80 study participants, including healthy controls and patients with MS in 6 DMT groups: untreated and treated with glatiramer acetate (GA), dimethyl fumarate (DMF), natalizumab (NTZ), sphingosine-1-phosphate (S1P) receptor modulators, and anti-CD20 mAbs. Anti–spike-Ab responses were assessed by Luminex assay, VirScan, and pseudovirus neutralization. Spike-specific CD4+ and CD8+ T cell responses were characterized by activation-induced marker and cytokine expression and tetramer.RESULTSAnti-spike IgG levels were similar between healthy control participants and patients with untreated MS and those receiving GA, DMF, or NTZ but were reduced in anti-CD20 mAb– and S1P-treated patients. Anti-spike seropositivity in anti-CD20 mAb–treated patients was correlated with CD19+ B cell levels and inversely correlated with cumulative treatment duration. Spike epitope reactivity and pseudovirus neutralization were reduced in anti-CD20 mAb– and S1P-treated patients. Spike-specific CD4+ and CD8+ T cell reactivity remained robust across all groups, except in S1P-treated patients, in whom postvaccine CD4+ T cell responses were attenuated.CONCLUSIONThese findings from a large cohort of patients with MS exposed to a wide spectrum of MS immunotherapies have important implications for treatment-specific COVID-19 clinical guidelines.FUNDINGNIH grants 1K08NS107619, K08NS096117, R01AI159260, R01NS092835, R01AI131624, and R21NS108159; NMSS grants TA-1903-33713 and RG1701-26628; Westridge Foundation; Chan Zuckerberg Biohub; Maisin Foundation.
Highlights
Multiple sclerosis (MS) is an inflammatory demyelinating condition of the central nervous system that is treated with more than 20 different, approved disease modifying therapies (DMTs) [1]
These findings from a large cohort of patients with MS exposed to a wide spectrum of MS immunotherapies have important implications for treatment-specific COVID-19 clinical guidelines
To study the effects of different MS DMTs on SARS-CoV-2 vaccine–induced immune responses, we recruited a cohort of 80 participants comprising healthy control individuals (HCs) (n = 13) and patients with MS who were receiving no treatment (n = 9) or were treated with glatiramer acetate (GA) (n = 5), dimethyl fumarate (DMF) (n = 5), NTZ (n = 6), S1P receptor modulators (n = 7), or anti-CD20 mAbs, including rituximab (RTX; n = 13) or ocrelizumab (OCR; n = 22) (Table 1)
Summary
Multiple sclerosis (MS) is an inflammatory demyelinating condition of the central nervous system that is treated with more than 20 different, approved disease modifying therapies (DMTs) [1]. MS DMTs differ considerably in their mechanisms of action, with variable impacts on humoral and cellular immune functions that can lead to associated risks of certain infections [2]. Control of SARS-Cov-2 infection involves mobilization of Ab- and T cell–mediated immunity [3–5]. Evidence suggests that patients with MS who receive anti-CD20 mAb therapies are at higher risk for hospitalization due to COVID-19 infection [6, 7]. Recent reports have demonstrated that patients with MS treated with an anti-CD20 mAb or S1P receptor modulators have reduced or undetectable spike antigen–specific IgG following COVID-19 infection [8–12]. Multiple sclerosis (MS) disease-modifying therapies (DMTs) differentially target humoral and cellular immunity. A comprehensive comparison of the effects of MS DMTs on SARS-CoV-2 vaccine–specific immunity is needed, including quantitative and functional B and T cell responses
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