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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
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.
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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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