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

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 anti‐spike 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; p = 0.005); and it was significantly higher in those immunized with rAd26/mRNA‐1273 (OR, 13.1; 95% CI, 2.3–72.9; p = 0.003). In LTRs anti‐spike IgG concentrations showed a very good correlation with NA titers (R (2) = 0.949; 95% CI, 0.919–0.967; p < 0.001). No serious adverse events were reported in either group. Conclusion: In LTRs, rAd26/mRNA‐1273 was independently associated with higher antibody response. Future studies are necessary to evaluate whether combining different vaccine platforms and MMF reduction may lead to a better booster response.