Background:

Vaccine-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 MS DMTs on SARS-CoV-2 vaccine-specific immunity is needed, including quantitative and functional B and T cell responses.


Methods:

Spike-specific antibody and T cell responses were measured before and following SARS-CoV-2 vaccination in a cohort of 80 subjects, including healthy controls and MS patients in six DMT groups: untreated, glatiramer acetate (GA), dimethyl fumarate (DMF), natalizumab (NTZ), sphingosine-1-phosphate (S1P) receptor modulators, and anti-CD20 monoclonal antibodies. Anti-spike antibody responses were quantified by Luminex assay, high-resolution spike epitope reactivity was mapped by VirScan, and pseudovirus neutralization was assessed. Spike-specific CD4+ and CD8+ T cell responses were characterized by activation-induced marker (AIM) expression, cytokine production, and tetramer analysis.


Results:

Anti-spike IgG levels were similar between healthy controls, untreated MS, GA, DMF, and NTZ patients, but were significantly reduced in anti-CD20 and S1P-treated patients. Anti-spike seropositivity in anti-CD20 patients was significantly correlated with CD19+ B cell levels and inversely correlated with cumulative treatment duration. Spike epitope reactivity and pseudovirus neutralization was reduced in anti-CD20 and S1P patients, directly correlating with reduced spike receptor binding domain (RBD) IgG levels. Spike-specific CD4+ and CD8+ T cell reactivity remained robust across all groups except in S1P-treated patients in whom post-vaccine CD4+ T cell responses were attenuated.


Conclusions:

These findings from a large MS cohort exposed to a wide spectrum of MS immunotherapies have important implications for treatment-specific COVID-19 clinical guidelines.


Funding:

This work was supported by grants from the NIH 1K08NS107619 (JJS), NMSS TA- 1903-33713 (JJS), K08NS096117 (MRW), Westridge Foundation (MRW), Chan Zuckerberg Biohub (JLD), R01AI159260 (JAH), R01NS092835 (SSZ), R01AI131624 (SSZ), R21NS108159 (SSZ), NMSS RG1701-26628 (SSZ), and the Maisin Foundation (SSZ).


Keywords:

Adaptive immunity; Autoimmunity; COVID-19; Multiple sclerosis.

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