Abstract
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 the effects of MS DMTs on SARS-CoV-2 vaccine–specific immunity is needed, including quantitative and functional B and T cell responses.METHODS Spike-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.RESULTS Anti-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.CONCLUSION 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.FUNDING NIH grants 1K08NS107619, K08NS096117, R01AI159260, R01NS092835, R01AI131624, and R21NS108159; NMSS grants TA-1903-33713 and RG1701-26628; Westridge Foundation; Chan Zuckerberg Biohub; Maisin Foundation.
Authors
Joseph J. Sabatino Jr., Kristen Mittl, William M. Rowles, Kira McPolin, Jayant V. Rajan, Matthew T. Laurie, Colin R. Zamecnik, Ravi Dandekar, Bonny D. Alvarenga, Rita P. Loudermilk, Chloe Gerungan, Collin M. Spencer, Sharon A. Sagan, Danillo G. Augusto, Jessa R. Alexander, Joseph L. DeRisi, Jill A. Hollenbach, Michael R. Wilson, Scott S. Zamvil, Riley Bove
This file is in Adobe Acrobat (PDF) format. If you have not installed and configured the Adobe Acrobat Reader on your system.
Having trouble reading a PDF?
PDFs are designed to be printed out and read, but if you prefer to read them online, you may find it easier if you increase the view size to 125%.
Having trouble saving a PDF?
Many versions of the free Acrobat Reader do not allow Save. You must instead save the PDF from the JCI Online page you downloaded it from. PC users: Right-click on the Download link and choose the option that says something like "Save Link As...". Mac users should hold the mouse button down on the link to get these same options.
Having trouble printing a PDF?
- Try printing one page at a time or to a newer printer.
- Try saving the file to disk before printing rather than opening it "on the fly." This requires that you configure your browser to "Save" rather than "Launch Application" for the file type "application/pdf", and can usually be done in the "Helper Applications" options.
- Make sure you are using the latest version of Adobe's Acrobat Reader.
