Heterologous adenovirus‐vector/messenger RNA regimen is associated with improved severe acute respiratory syndrome coronavirus 2 humoral response in liver transplant recipients

Abstract

Knowledge of the immunogenicity of vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in liver transplant recipients (LTRs) is mainly limited to messenger RNA (mRNA)-based types. We aimed to evaluate the humoral response in LTRs and to address the use of different doses of mycophenolate (MMF) on the probability of developing antispike immunoglobulin G (IgG). In this prospective cohort study, SARS-CoV-2 anti-spike IgG, neutralizing antibodies (NAs), and nucleocapsid protein (N) were evaluated in LTRs and healthy volunteers 21-90 days after receiving the second vaccine dose of either ChAdOx1 (AstraZeneca), rAd26-rAd5 (Sputnik V), inactivated BBIBP-CorV (Sinopharm), or the heterologous combination rAd26/mRNA-1273 (Sputnik V/Moderna). We collected information regarding clinical data and vaccine side effects. After excluding three LTRs due to a positive N test, 120 LTRs and 27 controls were analyzed. No significant differences were found among groups. Overall, 24 (89%) controls and 74 (62%) LTRs were positive for anti-spike IgG (p = 0.007). Among LTRs, those immunized with rAd26/mRNA-1273 presented significantly higher positive serology and NAs when compared with the homologous regimens (91% vs. 55%, p = 0.001; and 1182 IU/ml vs. 446 IU/ml, p = 0.002; respectively). In the multivariate analysis, humoral response was significantly reduced in LTRs who received higher doses of MMF (odds ratio [OR], 0.1; 95% confidence interval [CI], 0.03-0.3; p < 0.001) and with increased BMI (OR, 0.4; 95% CI, 0.2-0.7;

Seroconversion following a booster dose of COVID-19 vaccine in liver transplant recipients. A systematic review and meta-analysis

“…Understanding the mechanism of action of these drugs, may contribute to enhancement of vaccines efficacy. It is known that MMF inhibits proliferation of T-and B-lymphocytes and thereby suppresses cell-mediated immune responses and antibody formation [42,43]. Thus, although Sars-CoV-2 infection may have a generally mild course in the LT setting [44] it seems reasonable clinicians may consider the reduction of the daily dose [or (temporary) discontinuation, if feasible] of MMF during the COVID-19 vaccination period on individualized basis.…”

The impact of COVID-19 on liver transplantation: challenges and perspectives

“…The use of heterologous vaccines (combination of rAd26/mRNA-1273 (Sputnik/Moderna) was studied by Mendizabal et al The combination resulted in a higher level of anti-spike IgG in LT patients, when compared to the homologous regimens. 62 Conflicting data were demonstrated in another study that showed a lower humoral response and lower seropositivity in the heterologous group. However, this study including all solid organ transplantation patients.…”

SARS-CoV-2 vaccination in liver transplant recipients: We still haven't found what we are looking for

“…The reduced immune response was more frequent in patients who received mycophenolate mofetil (MMF), those with a shorter time to transplantation and in patients with older age or with renal impairment [ 3 , [5] , [6] , [7] , [8] , [9] , [10] , [11] ]. On the other hand, the improved immune response was described in patients who received heterologous adenovirus-vector/mRNA regimens [12] . Recent studies have demonstrated a robust efficacy of a third SARS-CoV-2 vaccination in LTR ( Table 1 ).…”

“…໿When the analysis was restricted to studies performed in LTR, the negative effect of MMF was consistent (OR=0.46; 95%CI 0.31–0.68; p<.001) [14] . In some studies, a dose-dependent impairment of the humoral response was observed, particularly when the daily dose of MMF was higher than 1000 mg per day [ 12 , 14 ]. The detrimental effects of an MMF-containing immunosuppressive regimen in the vaccination induced humoral immune response was also described in SOT recipients after vaccination against the influenza virus [15] .…”