Impact of multiple sclerosis disease-modifying therapies on SARS-CoV-2 vaccine-induced antibody and T cell immunity

Sabatino, Joseph J.; Mittl, Kristen; Rowles, William; Mcpolin, Kira; Rajan, Jayant V.; Zamecnik, Colin R.; Dandekar, Ravi; Alvarenga, Bonny D.; Loudermilk, Rita P.; Gerungan, Chloe; Spencer, Collin M.; Sagan, Sharon A.; Augusto, Danillo G.; Alexander, Jessa; Hollenbach, Jill A.; Wilson, Michael R.; Zamvil, Scott S.; Bove, Riley

Vaccine-elicited adaptive immunity is an essential prerequisite for effective prevention and control of coronavirus 19 (COVID-19). Treatment of multiple sclerosis (MS) involves a diverse array of disease-modifying therapies (DMTs) that target antibody and cell-mediated immunity, yet a comprehensive understanding of how MS DMTs impact SARS-CoV-2 vaccine responses is lacking. We completed a detailed analysis of SARS-CoV-2 vaccine-elicited spike antigen-specific IgG and T cell responses in a cohort of healthy controls and MS participants in six different treatment categories. Two specific DMT types, sphingosine-1-phosphate (S1P) receptor modulators and anti-CD20 monoclonal antibodies (mAb), resulted in significantly reduced spike-specific IgG responses. Longer duration of anti-CD20 mAb treatment prior to SARS-CoV-2 vaccination were associated with absent antibody responses. Except for reduced CD4+ T cell responses in S1P-treated patients, spike-specific CD4+ and CD8+ T cell reactivity remained robust across all MS treatment types. These findings have important implications for clinical practice guidelines and vaccination recommendations in MS patients and other immunosuppressed populations.