Abstract
Background: SARS-CoV-2 mRNA vaccination of healthy individuals is highly immunogenic and protective against severe COVID-19. However, there are limited data on how disease-modifying therapies (DMTs) alter SARS-CoV-2 mRNA vaccine immunogenicity in patients with autoimmune diseases.
Methods: As part of a prospective cohort study, we investigated the induction, stability and boosting of vaccine-specific antibodies, B cells and T cells in patients with multiple sclerosis (MS) on different DMTs after homologous primary, secondary and booster SARS-CoV-2 mRNA vaccinations. Of 126 patients with MS analysed, 105 received either anti-CD20-based B cell depletion (aCD20-BCD), fingolimod, interferon-β, dimethyl fumarate, glatiramer acetate, teriflunomide or natalizumab, and 21 were untreated MS patients for comparison.
Results: In contrast to all other MS patients, and even after booster, most aCD20-BCD- and fingolimod-treated patients showed no to markedly reduced anti-S1 IgG, serum neutralising activity and a lack of receptor binding domain-specific and S2-specific B cells. Patients receiving fingolimod additionally lacked spike-reactive CD4 + T cell responses. The duration of fingolimod treatment, rather than peripheral blood B and T cell counts prior to vaccination, determined whether a humoral immune response was elicited.
Conclusions: The lack of immunogenicity under long-term fingolimod treatment demonstrates that functional immune responses require not only immune cells themselves, but also access of these cells to the site of inoculation and their unimpeded movement. The absence of humoral and T cell responses suggests that fingolimod-treated patients with MS are at risk for severe SARS-CoV-2 infections despite booster vaccinations, which is highly relevant for clinical decision-making and adapted protective measures, particularly considering additional recently approved sphingosine-1-phosphate receptor antagonists for MS treatment.
Keywords: clinical neurology; immunology; infectious diseases; multiple sclerosis.
【저자키워드】 immunology, Infectious diseases, multiple sclerosis., clinical neurology, 【초록키워드】 Treatment, SARS-CoV-2, IgG, mRNA vaccination, vaccination, therapy, severe COVID-19, multiple sclerosis, mRNA vaccine, Infection, B cells, risk, prospective cohort study, CD4, Peripheral blood, B cell, serum, T cell, stability, Measures, mRNA, T cell responses, Patient, humoral immune response, receptor, Autoimmune diseases, homologous, patients, T cell response, booster, Protective, Neutralising activity, Acetate, Vaccinations, Immune cell, Receptor binding, humoral, fumarate, immunogenic, functional immune response, antagonist, booster vaccinations, Alter, severe SARS-CoV-2, lack, investigated, approved, receiving, analysed, reduced, absence, elicited, these cell, healthy individual, vaccine-specific antibodies, 【제목키워드】 SARS-CoV-2, mRNA vaccination, multiple sclerosis, Cellular immune response, Patient, humoral, receiving, elicit,