Mycophenolate mofetil decreases humoral responses to three doses of SARS‐CoV‐2 vaccine in liver transplant recipients

Abstract

Background and Aims After 2 doses, the efficacy of anti‐SARS‐CoV‐2 vaccination seems to be lower in solid organ transplant recipients than in the immunocompetent population. The objective of this study was to determine the humoral response rate after vaccination, including with a booster dose, and to identify risk factors for non‐responsiveness in liver transplant recipients. Methods We included all patients seen in consultation in two French liver transplant centres between January 1, 2021, and March 15, 2021. Results 598 liver transplant recipients were enrolled and 327 were included for analysis. Sixteen patients received one dose, 63 patients two doses and 248 patients three doses. Anti‐SARS‐Cov‐2 antibodies were detected in 242 out of 327 (74.0%) liver transplant patients after vaccination. Considering an optimal serologic response defined as an antibody titre >260 BAU/ml, 172 patients (52.6%) were responders. Mycophenolate mofetil (MMF) treatment was an independent risk factor for a failure to develop anti‐SARS‐CoV‐2 antibodies after vaccination (OR 0.458; 95%CI 0.258–0.813; p = .008). Conversely, male gender (OR 2.247, 95%CI 1.194–4.227; p = .012) and receiving an mRNA vaccine (vs a non‐mRNA vaccine) (OR 4.107, 95%CI 1.145–14.731; p = .030) were independent predictive factors for developing an optimal humoral response after vaccination. None of the patients who received the vaccine experienced any serious adverse events. Conclusions Even after a third booster dose, response rate to vaccination is decreased in liver transplant recipients. MMF appears to be a major determinant of seroconversion and optimal response to vaccination in these patients.

Mycophenolate and SARS‐CoV‐2 vaccination: Mixing oil and water

“…Although a prospective serological follow‐up was not performed beyond that point, previous studies suggest that levels of antibodies may experience a rapid decline from the first 3 months onwards, much faster than in immunocompetent individuals, with seroconversion rates halved at 12 months from the last dose 3 . One of the most relevant findings by Meunier et al was the strong association between the immunosuppressant mycophenolate mofetil (MMF) and an impaired humoral response after vaccination (OR 0.458; 95% CI 0.258–0.813; p = .008) 2 . The relationship between SARS‐CoV‐2 infection and MMF is intriguing and it may be related to a synergic effect of both agents on depleting lymphocytes, particularly in some subpopulations, 4 ultimately resulting in an aberrant immune response and increased risk of respiratory failure, admission to the intensive care unit and death 1 .…”

“…3 One of the most relevant findings by Meunier et al was the strong association between the immunosuppressant mycophenolate mofetil (MMF) and an impaired humoral response after vaccination (OR 0.458; 95% CI 0.258-0.813; p = .008). 2 The relationship between SARS-CoV-2 infection and MMF is intriguing and it may be related to a synergic effect of both agents on depleting lymphocytes, particularly in some subpopulations, 4 ultimately resulting in an aberrant immune response and increased risk of respiratory failure, admission to the intensive care unit and death. 1 The humoral immune response after SARS-CoV-2 vaccination may be equally abnormal in patients receiving MMF.…”

“…In general, the rates of seroconversion are increased after receiving mRNA-based vaccines compared to viral vector-based vaccines, although the number of patients in the latter group is probably insufficient to obtain solid conclusions. 2,11 The overall seroconversion rate ranged from 20.7% to 71.9% and most studies described reduced seroconversion (and lower serum concentration of antibodies) in patients receiving MMF compared to patients receiving MMF-free immunosuppression regimes. In some studies, a dose-dependent impairment of the humoral response was observed, 6,8,9,16 particularly when daily dose of MMF was higher than 1000 mg per day.…”

“…Have published an excellent study which evaluates the humoral response after vaccination against SARS-CoV-2 in LT patients. 2 The authors retrospectively analysed 327 patients, the largest cohort published hitherto, who received one, two or three doses of either BNT162b2 (Pfizer-BioNTech), mRNA-1273 (Moderna) or AZD1222 (Vaxzevria, Oxford-AstraZeneca). Three hundred and eight patients (94.2%) received mRNA-based vaccines (BNT162b2 or mRNA-1273), whereas 19 patients (5.8%) received the viral vector-based vaccine AZD1222.…”

“…In the last issue of Liver International , L. Meunier and cols. Have published an excellent study which evaluates the humoral response after vaccination against SARS‐CoV‐2 in LT patients 2 . The authors retrospectively analysed 327 patients, the largest cohort published hitherto, who received one, two or three doses of either BNT162b2 (Pfizer‐BioNTech), mRNA‐1273 (Moderna) or AZD1222 (Vaxzevria, Oxford‐AstraZeneca).…”