Multiple sclerosis therapies differentially affect SARS-CoV-2 vaccine–induced antibody and T cell immunity and function

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 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. Antispike 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.

Is humoral and cellular response to SARS-CoV-2 vaccine modified by DMT in patients with multiple sclerosis and other autoimmune diseases?

“…3,4 The cellular response after SARS-CoV-2 vaccination appeared to be preserved under most DMTs. 8,9 Conversely, <12% of SP1RM-treated patients mounted a cellular response regardless of their serostatus or lymphocyte count. As highlighted in some studies, anti-CD20s present a high percentage of cellular response rate even in the absence of a humoral response.…”

Cellular and Humoral Immunity to SARS‐CoV‐2 Infection in Multiple Sclerosis Patients on Ocrelizumab and Other Disease‐Modifying Therapies: A Multi‐Ethnic Observational Study

“… 11 , 12 Overall, T‐cells counts and functional responses remain intact, 13 , 14 and, accordingly, Spike protein‐specific T‐cell responses to coronavirus disease 2019 (COVID‐19) vaccination in aCD20‐treated patients are robust. 11 , 15 , 16 , 17 , 18 , 19 T‐cell responses following natural infection in aCD20‐treated patients have received less attention, but are an active area of investigation. 20 , 21 There is very limited data on immune responses to SARS‐CoV‐2 infection under other commonly used DMTs, such as sphingosine‐1‐phosphate receptor modulators (S1P), which interfere with T‐cell egress from lymphoid tissue, and fumarates, which induce mild–moderate lymphopenia.…”

Vaccination and immunotherapies in neuroimmunological diseases

“…Response rates were comparable between the two groups, ranging between 53% for meningococcal serogroup C and 95% for pneumococcal serotype 8. Overall, immune responses to vaccination seem to be maintained in patients treated with dimethyl fumarate 61 , 62 so no special measures are needed.…”

“…In this study, patients receiving anti-CD20 therapy had lower specific memory B cell responses to mRNA SARS-CoV-2 vaccination than did healthy control participants but their antigen-specific CD4 + T cell and CD8 + T cell responses were comparable to those of healthy control participants 206 . Overall, evidence suggests that antigen-specific CD4 + and CD8 + T cell responses after vaccination are adequate in patients with MS who are receiving anti-CD20 monoclonal antibodies despite poor spike-specific and receptor-binding domain-specific antibody production 62 , 206 , 207 . Other studies have shown that patients receiving treatment with fingolimod for MS had low humoral and T cell responses to mRNA or vectored SARS-CoV-2 vaccinations 62 , 209 .…”

“…Overall, evidence suggests that antigen-specific CD4 + and CD8 + T cell responses after vaccination are adequate in patients with MS who are receiving anti-CD20 monoclonal antibodies despite poor spike-specific and receptor-binding domain-specific antibody production 62 , 206 , 207 . Other studies have shown that patients receiving treatment with fingolimod for MS had low humoral and T cell responses to mRNA or vectored SARS-CoV-2 vaccinations 62 , 209 .…”