Impact of MS disease-modifying therapies on antibody and T cell responses following COVID-19 vaccination

Introduction: MS disease-modifying therapies (DMTs) lead to distinct effects on humoral and cellular immunity. Effective vaccine- elicited immunity to severe acute respiratory syndrome coronavirus- 2 (SARS-CoV-2), the causative agent of the ongoing COVID-19 pandemic, requires robust antibody and CD4+ and CD8+ T cell responses against the SARS-CoV-2 spike protein. Understanding how different MS DMTs affect COVID-19 vaccine immunity is a vital clinical gap that needs to be urgently addressed. Objectives: The goal of this study is to assess COVID-19 vaccine- elicited antibody and T cell responses in MS patients on different of DMTs. Aims: To measure SARS-CoV-2 spike antigen-specific antibody and CD4+ and CD8+ T cell responses before and after COVID- 19 vaccination of MS patients on different DMTs. Methods: Enrolment included MS patients on no therapy, or treated with glatiramer acetate (GA), dimethyl fumarate (DMF), natalizumab (NAT), sphingosine-1-phosphate receptor (S1P) modulator, or anti-CD20 monoclonal antibody (mAb). Serum and peripheral blood mononuclear cells (PBMCs) were collected from all patients before and 2-4 weeks following final COVID-19 vaccination. Patient serum was tested on a Luminex bead-based assay to quantitatively measure IgG levels against the whole SARSCoV- 2 spike protein and the spike receptor binding domain (RBD). PBMCs were stimulated with pools of SARS-CoV-2 spike peptides to measure the frequencies of spike-specific CD4+ and CD8+ T cells by activation-induced marker expression. Results: Following COVID-19 vaccination, all untreated MS patients and patients on GA, DMF, and NAT were seropositive with similar high IgG titres to total spike and spike RBD. MS patients on S1P modulators and anti-CD20 mAb exhibited significantly reduced IgG titres to total spike and spike RBD antigens, with only a fraction of patients reaching seropositivity. Spike antigen-specific CD4+ and CD8+ T cell responses were present at similar levels across all DMT categories following COVID-19 vaccination. Conclusions: MS DMTs exhibited differential effects on COVID- 19 vaccine-elicited humoral, but not T cell immunity. Whereas IgG responses were unaffected in MS patients on GA, DMF, and NAT, IgG levels were reduced in MS patients on S1P modulators and anti-CD20 mAb. The findings of this study have important clinical implications for assessing potential risk of COVID-19 infection in vaccinated MS patients on specific DMTs.