Short- and Long-Term Humoral and Cellular Immune Responses to SARS-CoV-2 Vaccination in Patients with Multiple Sclerosis Treated with Disease-Modifying Therapies
Susana Sainz de la Maza,
Paulette Esperanza Walo-Delgado,
Mario Rodríguez-Domínguez,
Enric Monreal,
Alexander Rodero-Romero,
Juan Luis Chico-García,
Roberto Pariente,
Fernando Rodríguez-Jorge,
Rubén Ballester-González,
Noelia Villarrubia,
Beatriz Romero-Hernández,
Jaime Masjuan,
Lucienne Costa-Frossard,
Luisa María Villar
Affiliations
Susana Sainz de la Maza
Department of Neurology, Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Red Española de Esclerosis Múltiple (REEM), Universidad de Alcalá, 28034 Madrid, Spain
Paulette Esperanza Walo-Delgado
Department of Immunology, Hospital Universitario Ramón y Cajal, Universidad de Alcalá, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Red Española de Esclerosis Múltiple (REEM), 28034 Madrid, Spain
Mario Rodríguez-Domínguez
Department of Microbiology, Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), CIBER en Epidemiología y Salud Pública (CIBERESP), 28034 Madrid, Spain
Enric Monreal
Department of Neurology, Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Red Española de Esclerosis Múltiple (REEM), Universidad de Alcalá, 28034 Madrid, Spain
Alexander Rodero-Romero
Department of Immunology, Hospital Universitario Ramón y Cajal, Universidad de Alcalá, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Red Española de Esclerosis Múltiple (REEM), 28034 Madrid, Spain
Juan Luis Chico-García
Department of Neurology, Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Red Española de Esclerosis Múltiple (REEM), Universidad de Alcalá, 28034 Madrid, Spain
Roberto Pariente
Department of Immunology, Hospital Universitario Ramón y Cajal, Universidad de Alcalá, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Red Española de Esclerosis Múltiple (REEM), 28034 Madrid, Spain
Fernando Rodríguez-Jorge
Department of Neurology, Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Red Española de Esclerosis Múltiple (REEM), Universidad de Alcalá, 28034 Madrid, Spain
Rubén Ballester-González
Department of Immunology, Hospital Universitario Ramón y Cajal, Universidad de Alcalá, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Red Española de Esclerosis Múltiple (REEM), 28034 Madrid, Spain
Noelia Villarrubia
Department of Immunology, Hospital Universitario Ramón y Cajal, Universidad de Alcalá, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Red Española de Esclerosis Múltiple (REEM), 28034 Madrid, Spain
Beatriz Romero-Hernández
Department of Microbiology, Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), CIBER en Epidemiología y Salud Pública (CIBERESP), 28034 Madrid, Spain
Jaime Masjuan
Department of Neurology, Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Red Española de Esclerosis Múltiple (REEM), Universidad de Alcalá, 28034 Madrid, Spain
Lucienne Costa-Frossard
Department of Neurology, Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Red Española de Esclerosis Múltiple (REEM), Universidad de Alcalá, 28034 Madrid, Spain
Luisa María Villar
Department of Immunology, Hospital Universitario Ramón y Cajal, Universidad de Alcalá, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Red Española de Esclerosis Múltiple (REEM), 28034 Madrid, Spain
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.