Impact of Maintenance Immunosuppression Regimen on Anti-SARS-CoV-2 Antibody Kinetics In Kidney Transplant Recipients Receiving ChAdOx1 as Primary Vaccination

Kidney transplant recipients (KTRs) are at high risk of severe COVID-19 outcomes due to chronic immunosuppression, which can impair vaccine efficacy. While mycophenolate sodium (MPS) and azathioprine (AZA) are commonly used immunosuppressive agents, their influence on anti-SARS-CoV-2 antibody kinetics remains unclear. This study compares the humoral response in KTRs receiving MPS or AZA after ChAdOx1 primary vaccination. Methods: This prospective, observational, single-center study included 89 KTRs who had undergone transplantation and seroconverted following ChAdOx1 vaccination. Patients were grouped based on maintenance immunosuppression: MPS (n=51) or AZA (n=38). Anti-SARS-CoV-2 IgG titers and neutralizing antibody activity were measured at screening and 1-, 3-, 6-, and 12-months post-transplant. Linear regression models and generalized estimating equations were applied to analyze group and time effects. Results: At baseline, IgG titers were 12,059.2 AU/mL (MPS) and 14,369.3 AU/mL (AZA), with both groups experiencing a decline at month 1 (9,483.9 AU/mL and 11,023.5 AU/mL, respectively). By month 12, titers stabilized at 11,626.8 AU/mL (MPS) and 13,851.4 AU/mL (AZA; p=0.286). Neutralizing antibody activity was initially higher in the AZA group (0.924 vs. 0.764 at baseline; p=0.006) but converged with the MPS group by month 3 (0.937 vs. 0.871; p=0.161). Booster doses significantly enhanced responses, with a mean gain of 0.175 in neutralizing activity over 12 months. Conclusions: AZA offers a transient early advantage in humoral responses compared to MPS, but long-term antibody kinetics were comparable. Booster doses are critical for sustaining immunity in KTRs, underscoring the need for tailored vaccination strategies in this population. These findings may guide clinical decisions during pandemic scenarios.