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Dose-Dependent Impairment of the Immune Response to the Moderna-1273 mRNA Vaccine by Mycophenolate Mofetil in Patients with Rheumatic and Autoimmune Liver Diseases
The purpose of this study was to evaluate the efficacy and safety of the Moderna-1273 mRNA vaccine for SARS-CoV-2 in patients with immune-mediated diseases under different treatments. Anti-trimeric spike protein antibodies were tested in 287 patients with rheumatic or autoimmune diseases (10% receiv...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9144166/ https://www.ncbi.nlm.nih.gov/pubmed/35632557 http://dx.doi.org/10.3390/vaccines10050801 |
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author | De Santis, Maria Motta, Francesca Isailovic, Natasa Clementi, Massimo Criscuolo, Elena Clementi, Nicola Tonutti, Antonio Rodolfi, Stefano Barone, Elisa Colapietro, Francesca Ceribelli, Angela Vecellio, Matteo Luciano, Nicoletta Guidelli, Giacomo Caprioli, Marta Rezk, Clara Canziani, Lorenzo Azzolini, Elena Germagnoli, Luca Mancini, Nicasio Lleo, Ana Selmi, Carlo |
author_facet | De Santis, Maria Motta, Francesca Isailovic, Natasa Clementi, Massimo Criscuolo, Elena Clementi, Nicola Tonutti, Antonio Rodolfi, Stefano Barone, Elisa Colapietro, Francesca Ceribelli, Angela Vecellio, Matteo Luciano, Nicoletta Guidelli, Giacomo Caprioli, Marta Rezk, Clara Canziani, Lorenzo Azzolini, Elena Germagnoli, Luca Mancini, Nicasio Lleo, Ana Selmi, Carlo |
author_sort | De Santis, Maria |
collection | PubMed |
description | The purpose of this study was to evaluate the efficacy and safety of the Moderna-1273 mRNA vaccine for SARS-CoV-2 in patients with immune-mediated diseases under different treatments. Anti-trimeric spike protein antibodies were tested in 287 patients with rheumatic or autoimmune diseases (10% receiving mycophenolate mofetil, 15% low-dose glucocorticoids, 21% methotrexate, and 58% biologic/targeted synthetic drugs) at baseline and in 219 (76%) 4 weeks after the second Moderna-1273 mRNA vaccine dose. Family members or caretakers were enrolled as the controls. The neutralizing serum activity against SARS-CoV-2-G614, alpha, and beta variants in vitro and the cytotoxic T cell response to SARS-CoV-2 peptides were determined in a subgroup of patients and controls. Anti-SARS-CoV-2 antibody development, i.e., seroconversion, was observed in 69% of the mycophenolate-treated patients compared to 100% of both the patients taking other treatments and the controls (p < 0.0001). A dose-dependent impairment of the humoral response was observed in the mycophenolate-treated patients. A daily dose of >1 g at vaccination was a significant risk factor for non-seroconversion (ROC AUC 0.89, 95% CI 0.80–98, p < 0.0001). Moreover, in the seroconverted patients, a daily dose of >1 g of mycophenolate was associated with significantly lower anti-SARS-CoV-2 antibody titers, showing slightly reduced neutralizing serum activity but a comparable cytotoxic response compared to other immunosuppressants. In non-seroconverted patients treated with mycophenolate at a daily dose of >1 g, the cytotoxic activity elicited by viral peptides was also impaired. Mycophenolate treatment affects the Moderna-1273 mRNA vaccine immunogenicity in a dose-dependent manner, independent of rheumatological disease. |
format | Online Article Text |
id | pubmed-9144166 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-91441662022-05-29 Dose-Dependent Impairment of the Immune Response to the Moderna-1273 mRNA Vaccine by Mycophenolate Mofetil in Patients with Rheumatic and Autoimmune Liver Diseases De Santis, Maria Motta, Francesca Isailovic, Natasa Clementi, Massimo Criscuolo, Elena Clementi, Nicola Tonutti, Antonio Rodolfi, Stefano Barone, Elisa Colapietro, Francesca Ceribelli, Angela Vecellio, Matteo Luciano, Nicoletta Guidelli, Giacomo Caprioli, Marta Rezk, Clara Canziani, Lorenzo Azzolini, Elena Germagnoli, Luca Mancini, Nicasio Lleo, Ana Selmi, Carlo Vaccines (Basel) Article The purpose of this study was to evaluate the efficacy and safety of the Moderna-1273 mRNA vaccine for SARS-CoV-2 in patients with immune-mediated diseases under different treatments. Anti-trimeric spike protein antibodies were tested in 287 patients with rheumatic or autoimmune diseases (10% receiving mycophenolate mofetil, 15% low-dose glucocorticoids, 21% methotrexate, and 58% biologic/targeted synthetic drugs) at baseline and in 219 (76%) 4 weeks after the second Moderna-1273 mRNA vaccine dose. Family members or caretakers were enrolled as the controls. The neutralizing serum activity against SARS-CoV-2-G614, alpha, and beta variants in vitro and the cytotoxic T cell response to SARS-CoV-2 peptides were determined in a subgroup of patients and controls. Anti-SARS-CoV-2 antibody development, i.e., seroconversion, was observed in 69% of the mycophenolate-treated patients compared to 100% of both the patients taking other treatments and the controls (p < 0.0001). A dose-dependent impairment of the humoral response was observed in the mycophenolate-treated patients. A daily dose of >1 g at vaccination was a significant risk factor for non-seroconversion (ROC AUC 0.89, 95% CI 0.80–98, p < 0.0001). Moreover, in the seroconverted patients, a daily dose of >1 g of mycophenolate was associated with significantly lower anti-SARS-CoV-2 antibody titers, showing slightly reduced neutralizing serum activity but a comparable cytotoxic response compared to other immunosuppressants. In non-seroconverted patients treated with mycophenolate at a daily dose of >1 g, the cytotoxic activity elicited by viral peptides was also impaired. Mycophenolate treatment affects the Moderna-1273 mRNA vaccine immunogenicity in a dose-dependent manner, independent of rheumatological disease. MDPI 2022-05-18 /pmc/articles/PMC9144166/ /pubmed/35632557 http://dx.doi.org/10.3390/vaccines10050801 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article De Santis, Maria Motta, Francesca Isailovic, Natasa Clementi, Massimo Criscuolo, Elena Clementi, Nicola Tonutti, Antonio Rodolfi, Stefano Barone, Elisa Colapietro, Francesca Ceribelli, Angela Vecellio, Matteo Luciano, Nicoletta Guidelli, Giacomo Caprioli, Marta Rezk, Clara Canziani, Lorenzo Azzolini, Elena Germagnoli, Luca Mancini, Nicasio Lleo, Ana Selmi, Carlo Dose-Dependent Impairment of the Immune Response to the Moderna-1273 mRNA Vaccine by Mycophenolate Mofetil in Patients with Rheumatic and Autoimmune Liver Diseases |
title | Dose-Dependent Impairment of the Immune Response to the Moderna-1273 mRNA Vaccine by Mycophenolate Mofetil in Patients with Rheumatic and Autoimmune Liver Diseases |
title_full | Dose-Dependent Impairment of the Immune Response to the Moderna-1273 mRNA Vaccine by Mycophenolate Mofetil in Patients with Rheumatic and Autoimmune Liver Diseases |
title_fullStr | Dose-Dependent Impairment of the Immune Response to the Moderna-1273 mRNA Vaccine by Mycophenolate Mofetil in Patients with Rheumatic and Autoimmune Liver Diseases |
title_full_unstemmed | Dose-Dependent Impairment of the Immune Response to the Moderna-1273 mRNA Vaccine by Mycophenolate Mofetil in Patients with Rheumatic and Autoimmune Liver Diseases |
title_short | Dose-Dependent Impairment of the Immune Response to the Moderna-1273 mRNA Vaccine by Mycophenolate Mofetil in Patients with Rheumatic and Autoimmune Liver Diseases |
title_sort | dose-dependent impairment of the immune response to the moderna-1273 mrna vaccine by mycophenolate mofetil in patients with rheumatic and autoimmune liver diseases |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9144166/ https://www.ncbi.nlm.nih.gov/pubmed/35632557 http://dx.doi.org/10.3390/vaccines10050801 |
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