Dose-Dependent Impairment of the Immune Response to the Moderna-1273 mRNA Vaccine by Mycophenolate Mofetil in Patients with Rheumatic and Autoimmune Liver Diseases

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.

Humoral Immunogenicity of mRNA Booster Vaccination after Heterologous CoronaVac-ChAdOx1 nCoV-19 or Homologous ChAdOx1 nCoV-19 Vaccination in Patients with Autoimmune Rheumatic Diseases: A Preliminary Report

“…Previous studies have revealed that it impacts the effects of SARS-CoV-2 vaccination, including primary series and mRNA-based vaccine booster schemes. The seroconversion rate and anti-SARS-CoV-2 IgG levels decreased in patients with ARDs receiving mycophenolate mofetil in a dose-dependent manner, especially for a daily dose of >1 gm per day [ 21 ]. The impairment of humoral immunogenicity after vaccination in mycophenolate mofetil users can be attributed to the inhibition of B cells.…”

Spike-specific T-cell responses in patients with COVID-19 successfully treated with neutralizing monoclonal antibodies against SARS-CoV-2

“…This patient did not show any significant increase in T-cell markers, which was correlated with the clinical progression of COVID-19. While tacrolimus is not associated with severe disease or increased risk of death in COVID-19 patients (Yin et al, 2021), mycophenolate can cause T-cell depletion and impairment of immune response to SARS-CoV-2 (De Santis et al, 2022).…”

Impact of Immunomodulatory Therapy on COVID-19 Vaccine Response in Patients with Autoimmune Inflammatory Rheumatic Diseases

“…MMF treatment has been shown to significantly reduce seroconversion rates (69% in MMF group vs. 100% in healthy controls, p < 0.001) and antibody titres in response to the Moderna COVID-19 (mRNA1273) vaccine, with a notable dose-dependent effect. This effect was most pronounced in patients receiving over 1 g daily, leading to both reduced neutralising activity and impaired cytotoxic cellular response [ 36 ]. A similar dose-dependent impact on humoral immune response was observed in another study [ 37 ].…”