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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

Authors :
Maria De Santis
Francesca Motta
Natasa Isailovic
Massimo Clementi
Elena Criscuolo
Nicola Clementi
Antonio Tonutti
Stefano Rodolfi
Elisa Barone
Francesca Colapietro
Angela Ceribelli
Matteo Vecellio
Nicoletta Luciano
Giacomo Guidelli
Marta Caprioli
Clara Rezk
Lorenzo Canziani
Elena Azzolini
Luca Germagnoli
Nicasio Mancini
Ana Lleo
Carlo Selmi
Source :
Vaccines, Vol 10, Iss 5, p 801 (2022)
Publication Year :
2022
Publisher :
MDPI AG, 2022.

Abstract

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.

Details

Language :
English
ISSN :
2076393X
Volume :
10
Issue :
5
Database :
Directory of Open Access Journals
Journal :
Vaccines
Publication Type :
Academic Journal
Accession number :
edsdoj.9d2389a2c7b544fe86132caa68c4526a
Document Type :
article
Full Text :
https://doi.org/10.3390/vaccines10050801