Short- and Long-Term Humoral and Cellular Immune Responses to SARS-CoV-2 Vaccination in Patients with Multiple Sclerosis Treated with Disease-Modifying Therapies

Abstract

Background: This study aimed to evaluate short- and long-term humoral and T-cell-specific immune responses to SARS-CoV-2 vaccines in patients with multiple sclerosis (MS) treated with different disease-modifying therapies (DMTs).

Methods: Single-center observational longitudinal study including 102 patients with MS who consecutively received vaccination against SARS-CoV-2. Serum samples were collected at baseline and after receiving the second dose of the vaccine. Specific Th1 responses following in vitro stimulation with spike and nucleocapsid peptides were analyzed by quantifying levels of IFN-γ. Serum IgG-type antibodies against the spike region of SARS-CoV-2 were studied by chemiluminescent microparticle immunoassay.

Results: Patients undergoing fingolimod and anti-CD20 therapies had a markedly lower humoral response than those treated with other DMTs and untreated patients. Robust antigen-specific T-cell responses were detected in all patients except those treated with fingolimod, who had lower IFN-γ levels than those treated with other DMTs (25.8 pg/mL vs. 868.7 pg/mL, p = 0.011). At mid-term follow-up, a decrease in vaccine-induced anti-SARS-CoV-2 IgG antibodies was observed in all subgroups of patients receiving DMTs, although most patients receiving induction DMTs or natalizumab and non-treated patients remained protected. Cellular immunity was maintained above protective levels in all DMT subgroups except the fingolimod subgroup.

Conclusions: SARS-CoV-2 vaccines induce robust and long-lasting humoral and cell-mediated specific immune responses in most patients with MS.

Keywords: COVID19; SARS-CoV-2 vaccination; disease-modifying therapies; immune response; multiple sclerosis.

Figure 1

Post-vaccination anti-SARS-CoV-2 IgG titers (A) and IFN-γ levels (B) by disease-modifying therapy. (A) The lower dotted line marks anti-spike IgG antibody titers considered positive (7.1 BAU/mL), and the upper dotted line marks anti-spike IgG antibody titers considered protective (260 BAU/mL). (B) Dotted line marks IFN-γ levels of 80 pg/mL that were considered positive. ALEM: alemtuzumab; CLAD: cladribine; FING: fingolimod; FLT: first-line therapies; NATA: natalizumab; NTP: non-treated patients; OCRE: ocrelizumab; RITU: rituximab.

Figure 2

Concordance between cellular and humoral responses. Black dots indicate patients who developed a protective humoral response. Red dots indicate patients who did not develop a protective humoral response. Dotted line marks IFN-γ levels of 80 pg/mL that were considered positive. ALEM: alemtuzumab; CLAD: cladribine; FING: fingolimod; FLT: first-line therapies; NATA: natalizumab; NTP: non-treated patients; OCRE: ocrelizumab; RITU: rituximab.

Figure 3

Anti-SARS-CoV-2 IgG titers (A) and IFN-γ levels (B) in the early and late samples of patients classified according to their DMTs. (A) Dotted line marks anti-spike IgG antibody titers considered protective (260 BAU/mL). (B) Dotted line marks IFN-γ levels of 80 pg/mL that were considered positive. ACD20: anti-CD20 therapies; ALE: alemtuzumab CLAD: cladribine; E: early sample; FIN: fingolimod; FLT: first-line therapies; L: late sample; NAT: natalizumab; NTP: non-treated patients.

Figure 4

Post-vaccination anti-SARS-CoV-2 IgG titers (A) and IFN-γ levels (B) in relation to absolute lymphocyte counts: >800 cells/μL (gray dot), 500–799 cells/μL (red dot) and <500 cells/μL (green dot). (A) The lower dotted line marks anti-spike IgG antibody titers considered positive (7.1 BAU/mL), and the upper dotted line marks anti-spike IgG antibody titers considered protective (260 BAU/mL). (B) Dotted line marks IFN-γ levels of 80 pg/mL that were considered positive. ALEM: alemtuzumab; CLAD: cladribine; FING: fingolimod; FLT: first-line therapies; NATA: natalizumab; NTP: non-treated patients; OCRE: ocrelizumab; RITU: rituximab.

Figure 5

IFN-γ levels measured after in vitro stimulation of nucleocapsid (A) and spike peptides (B), in baseline and post-vaccination samples, in patients with or without prior COVID19. BL: baseline sample; C+: prior COVID-19; C−: without prior COVID-19; N: nucleocapsid; NS: non-significant; POST: post-vaccination sample; S: spike.