Natacha Madelon1, Kim Lauper2, Gautier Breville3, Irène Sabater Royo1, Rachel Goldstein1, Diego O Andrey4, Alba Grifoni5, Alessandro Sette6, Laurent Kaiser7, Claire Anne Siegrist1,8, Axel Finckh2, Patrice H Lalive9, Arnaud M Didierlaurent1, Christiane S Eberhardt1,8,10. 1. Center for Vaccinology, Department of Pathology and Immunology, University of Geneva, Geneva, Switzerland. 2. Department of Medicine, Division of Rheumatology, Geneva University Hospitals and University of Geneva, Geneva, Switzerland. 3. Department of Neurosciences, Division of Neurology, Geneva University Hospitals and University of Geneva, Geneva, Switzerland. 4. Department of Diagnostics, Division of Laboratory Medicine; Geneva University Hospitals and University of Geneva, Geneva, Switzerland. 5. Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, University of California, San Diego, La Jolla, California, USA. 6. Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology; Department of Medicine, Division of Infectious Diseases and Global Public Health, University of California, San Diego, La Jolla, California, USA. 7. Geneva Centre for Emerging Viral Diseases, Division of Infectious Diseases, Laboratory of Virology, Division of Laboratory Medicine, Geneva University Hospitals and University of Geneva, Geneva, Switzerland. 8. Center for Vaccinology, Geneva University Hospitals and Department of Woman, Child and Adolescent Medicine, Division of General Pediatrics, University of Geneva, Geneva, Switzerland. 9. Department of Neurosciences, Division of Neurology, Department of Pathology and Immunology, Geneva University Hospitals and University of Geneva, Geneva, Switzerlandand. 10. Emory Vaccine Center, Emory University School of Medicine, Atlanta, Georgia, USA.
Abstract
BACKGROUND: Patients treated with anti-CD20 therapy are particularly at risk of developing severe coronavirus disease 2019 (COVID-19); however, little is known regarding COVID-19 vaccine effectiveness in this population. METHODS: This prospective observational cohort study assesses humoral and T-cell responses after vaccination with 2 doses of mRNA-based COVID-19 vaccines in patients treated with rituximab for rheumatic diseases or ocrelizumab for multiple sclerosis (n = 37), compared to immunocompetent individuals (n = 22). RESULTS: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific antibodies were detectable in only 69.4% of patients and at levels that were significantly lower compared to controls who all seroconverted. In contrast to antibodies, Spike (S)-specific CD4 T cells were equally detected in immunocompetent and anti-CD20 treated patients (85-90%) and mostly of a Th1 phenotype. Response rates of S-specific CD8 T cells were higher in ocrelizumab (96.2%) and rituximab-treated patients (81.8%) as compared to controls (66.7%). S-specific CD4 and CD8 T cells were polyfunctional but expressed more effector molecules in patients than in controls. During follow-up, 3 MS patients without SARS-CoV-2-specific antibody response had a mild breakthrough infection. One of them had no detectable S-specific T cells after vaccination. CONCLUSIONS: Our study suggests that patients on anti-CD20 treatment are able to mount potent T-cell responses to mRNA COVID-19 vaccines, despite impaired humoral responses. This could play an important role in the reduction of complications of severe COVID-19.
BACKGROUND: Patients treated with anti-CD20 therapy are particularly at risk of developing severe coronavirus disease 2019 (COVID-19); however, little is known regarding COVID-19 vaccine effectiveness in this population. METHODS: This prospective observational cohort study assesses humoral and T-cell responses after vaccination with 2 doses of mRNA-based COVID-19 vaccines in patients treated with rituximab for rheumatic diseases or ocrelizumab for multiple sclerosis (n = 37), compared to immunocompetent individuals (n = 22). RESULTS: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific antibodies were detectable in only 69.4% of patients and at levels that were significantly lower compared to controls who all seroconverted. In contrast to antibodies, Spike (S)-specific CD4 T cells were equally detected in immunocompetent and anti-CD20 treated patients (85-90%) and mostly of a Th1 phenotype. Response rates of S-specific CD8 T cells were higher in ocrelizumab (96.2%) and rituximab-treated patients (81.8%) as compared to controls (66.7%). S-specific CD4 and CD8 T cells were polyfunctional but expressed more effector molecules in patients than in controls. During follow-up, 3 MS patients without SARS-CoV-2-specific antibody response had a mild breakthrough infection. One of them had no detectable S-specific T cells after vaccination. CONCLUSIONS: Our study suggests that patients on anti-CD20 treatment are able to mount potent T-cell responses to mRNA COVID-19 vaccines, despite impaired humoral responses. This could play an important role in the reduction of complications of severe COVID-19.
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