Immunity following SARS-CoV-2 vaccination in autoimmune neurological disorders treated with rituximab or ocrelizumab

BackgroundRituximab (RTX) and ocrelizumab (OCR), B cell-depleting therapy targeting CD20 molecules, affect the humoral immune response after vaccination. How these therapies influence T-cell-mediated immune response against SARS-CoV-2 after immunization remains unclear. We aimed to evaluate the humo...

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Main Authors: Petra Nytrova, Dominika Stastna, Adam Tesar, Ingrid Menkyova, Helena Posova, Helena Koprivova, Veronika Mikulova, Jiri Hrdy, Gabriela Smela, Dana Horakova, Irena Rysankova, Kristyna Doleckova, Michaela Tyblova
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-06-01
Series:Frontiers in Immunology
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Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2023.1149629/full
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author Petra Nytrova
Dominika Stastna
Adam Tesar
Adam Tesar
Ingrid Menkyova
Ingrid Menkyova
Helena Posova
Helena Koprivova
Veronika Mikulova
Jiri Hrdy
Gabriela Smela
Dana Horakova
Irena Rysankova
Kristyna Doleckova
Michaela Tyblova
author_facet Petra Nytrova
Dominika Stastna
Adam Tesar
Adam Tesar
Ingrid Menkyova
Ingrid Menkyova
Helena Posova
Helena Koprivova
Veronika Mikulova
Jiri Hrdy
Gabriela Smela
Dana Horakova
Irena Rysankova
Kristyna Doleckova
Michaela Tyblova
author_sort Petra Nytrova
collection DOAJ
description BackgroundRituximab (RTX) and ocrelizumab (OCR), B cell-depleting therapy targeting CD20 molecules, affect the humoral immune response after vaccination. How these therapies influence T-cell-mediated immune response against SARS-CoV-2 after immunization remains unclear. We aimed to evaluate the humoral and cellular immune response to the COVID-19 vaccine in a cohort of patients with multiple sclerosis (MS), neuromyelitis optica spectrum disorders (NMOSD), and myasthenia gravis (MG).MethodsPatients with MS (83), NMOSD (19), or MG (7) undergoing RTX (n=47) or OCR (n=62) treatment were vaccinated twice with the mRNA BNT162b2 vaccine. Antibodies were quantified using the SARS-CoV-2 IgG chemiluminescence immunoassay, targeting the spike protein. SARS-CoV-2-specific T cell responses were quantified by interferon γ release assays (IGRA). The responses were evaluated at two different time points (4-8 weeks and 16-20 weeks following the 2nd dose of the vaccine). Immunocompetent vaccinated individuals (n=41) were included as controls.ResultsAlmost all immunocompetent controls developed antibodies against the SARS-CoV-2 trimeric spike protein, but only 34.09% of the patients, without a COVID-19 history and undergoing anti-CD20 treatment (via RTX or OCR), seroconverted. This antibody response was higher in patients with intervals of longer than 3 weeks between vaccinations. The duration of therapy was significantly shorter in seroconverted patients (median 24 months), than in the non-seroconverted group. There was no correlation between circulating B cells and the levels of antibodies. Even patients with a low proportion of circulating CD19+ B cells (<1%, 71 patients) had detectable SARS-CoV-2 specific antibody responses. SARS-CoV-2 specific T cell response measured by released interferon γ was detected in 94.39% of the patients, independently of a humoral immune response.ConclusionThe majority of MS, MG, and NMOSD patients developed a SARS-CoV-2-specific T cell response. The data suggest that vaccination can induce SARS-CoV-2-specific antibodies in a portion of anti-CD20 treated patients. The seroconversion rate was higher in OCR-treated patients compared to those on RTX. The response represented by levels of antibodies was better in individuals, with intervals of longer than 3 weeks between vaccinations.
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spelling doaj.art-fd83e3caa4d14846b4d386ffddd286ce2023-06-16T05:42:51ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-06-011410.3389/fimmu.2023.11496291149629Immunity following SARS-CoV-2 vaccination in autoimmune neurological disorders treated with rituximab or ocrelizumabPetra Nytrova0Dominika Stastna1Adam Tesar2Adam Tesar3Ingrid Menkyova4Ingrid Menkyova5Helena Posova6Helena Koprivova7Veronika Mikulova8Jiri Hrdy9Gabriela Smela10Dana Horakova11Irena Rysankova12Kristyna Doleckova13Michaela Tyblova14Department of Neurology and Centre of Clinical Neuroscience, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, CzechiaDepartment of Neurology and Centre of Clinical Neuroscience, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, CzechiaDepartment of Neurology and Centre of Clinical Neuroscience, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, CzechiaInstitute of Biophysics and Informatics of the First Faculty of Medicine, Charles University in Prague, Prague, CzechiaDepartment of Neurology and Centre of Clinical Neuroscience, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czechia2nd Department of Neurology, Faculty of Medicine, Comenius University, Bratislava, SlovakiaLaboratory of Clinical Immunology and Allergology, Institute of Clinical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, CzechiaLaboratory of Clinical Immunology and Allergology, Institute of Clinical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, CzechiaLaboratory of Clinical Immunology and Allergology, Institute of Clinical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, CzechiaInstitute of Immunology and Microbiology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, CzechiaLaboratory of Clinical Immunology and Allergology, Institute of Clinical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, CzechiaDepartment of Neurology and Centre of Clinical Neuroscience, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, CzechiaDepartment of Neurology and Centre of Clinical Neuroscience, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, CzechiaDepartment of Neurology and Centre of Clinical Neuroscience, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, CzechiaDepartment of Neurology and Centre of Clinical Neuroscience, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, CzechiaBackgroundRituximab (RTX) and ocrelizumab (OCR), B cell-depleting therapy targeting CD20 molecules, affect the humoral immune response after vaccination. How these therapies influence T-cell-mediated immune response against SARS-CoV-2 after immunization remains unclear. We aimed to evaluate the humoral and cellular immune response to the COVID-19 vaccine in a cohort of patients with multiple sclerosis (MS), neuromyelitis optica spectrum disorders (NMOSD), and myasthenia gravis (MG).MethodsPatients with MS (83), NMOSD (19), or MG (7) undergoing RTX (n=47) or OCR (n=62) treatment were vaccinated twice with the mRNA BNT162b2 vaccine. Antibodies were quantified using the SARS-CoV-2 IgG chemiluminescence immunoassay, targeting the spike protein. SARS-CoV-2-specific T cell responses were quantified by interferon γ release assays (IGRA). The responses were evaluated at two different time points (4-8 weeks and 16-20 weeks following the 2nd dose of the vaccine). Immunocompetent vaccinated individuals (n=41) were included as controls.ResultsAlmost all immunocompetent controls developed antibodies against the SARS-CoV-2 trimeric spike protein, but only 34.09% of the patients, without a COVID-19 history and undergoing anti-CD20 treatment (via RTX or OCR), seroconverted. This antibody response was higher in patients with intervals of longer than 3 weeks between vaccinations. The duration of therapy was significantly shorter in seroconverted patients (median 24 months), than in the non-seroconverted group. There was no correlation between circulating B cells and the levels of antibodies. Even patients with a low proportion of circulating CD19+ B cells (<1%, 71 patients) had detectable SARS-CoV-2 specific antibody responses. SARS-CoV-2 specific T cell response measured by released interferon γ was detected in 94.39% of the patients, independently of a humoral immune response.ConclusionThe majority of MS, MG, and NMOSD patients developed a SARS-CoV-2-specific T cell response. The data suggest that vaccination can induce SARS-CoV-2-specific antibodies in a portion of anti-CD20 treated patients. The seroconversion rate was higher in OCR-treated patients compared to those on RTX. The response represented by levels of antibodies was better in individuals, with intervals of longer than 3 weeks between vaccinations.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1149629/fullSARS-CoV-2 mRNA vaccineSARS-CoV-2humoral immune responseIFN gamma release assaymyasthenia gravismultiple sclerosis
spellingShingle Petra Nytrova
Dominika Stastna
Adam Tesar
Adam Tesar
Ingrid Menkyova
Ingrid Menkyova
Helena Posova
Helena Koprivova
Veronika Mikulova
Jiri Hrdy
Gabriela Smela
Dana Horakova
Irena Rysankova
Kristyna Doleckova
Michaela Tyblova
Immunity following SARS-CoV-2 vaccination in autoimmune neurological disorders treated with rituximab or ocrelizumab
Frontiers in Immunology
SARS-CoV-2 mRNA vaccine
SARS-CoV-2
humoral immune response
IFN gamma release assay
myasthenia gravis
multiple sclerosis
title Immunity following SARS-CoV-2 vaccination in autoimmune neurological disorders treated with rituximab or ocrelizumab
title_full Immunity following SARS-CoV-2 vaccination in autoimmune neurological disorders treated with rituximab or ocrelizumab
title_fullStr Immunity following SARS-CoV-2 vaccination in autoimmune neurological disorders treated with rituximab or ocrelizumab
title_full_unstemmed Immunity following SARS-CoV-2 vaccination in autoimmune neurological disorders treated with rituximab or ocrelizumab
title_short Immunity following SARS-CoV-2 vaccination in autoimmune neurological disorders treated with rituximab or ocrelizumab
title_sort immunity following sars cov 2 vaccination in autoimmune neurological disorders treated with rituximab or ocrelizumab
topic SARS-CoV-2 mRNA vaccine
SARS-CoV-2
humoral immune response
IFN gamma release assay
myasthenia gravis
multiple sclerosis
url https://www.frontiersin.org/articles/10.3389/fimmu.2023.1149629/full
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