Introduction: Humoral and cellular immune response of adult kidney recipients to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) vaccination is reduced resulting in more intensive vaccination regimens. After pediatric kidney transplantation there are only few data available - mostly limited to monitoring of SARS-CoV-2 antibodies.
Methods: Humoral and cellular response has been monitored before and after SARS-CoV 2 vaccination (≥ 2 doses of mRNA vaccine Comirnaty®) in pediatric kidney recipients. After in vitro stimulation with SARS-CoV-2 antigen (spike glycoprotein) virus-specific CD4 and CD8 T cells (SARS-CoV-2-Tvis) have been identified by intracellular cytokine staining followed by flow cytometry. SARS-CoV-2 immunoglobulin G (IgG) against spike protein was measured by CMIA (chemiluminescent microparticle immunoassay). In case of SARS-CoV-2 infection, patients dropped out.
Results: Immune response after SARS-CoV-2 vaccination was analysed in a total of 30 pediatric kidney transplant recipients (age at 1st vaccine dose 5.2-17.8 years, median 14.8 years; 43% male; 30/30 2 vaccine doses; 23/30 3 vaccine doses). At time of vaccination 22 patients (73%) received a tacrolimus (Tac)-based immunosuppression combined with mycophenolate mofetil (MMF; n=15) or everolimus (Eve; n=6) or neither of them (n=1); 3 patients were exposed to cyclosporine A (CsA) and 5 patients to a calcineurin inhibitor (CNI)-free immunosuppression. MMF was used in 18/30 patients.
After 1st dose of mRNA vaccine SARS-CoV-2 antibodies were detectable in 50% of pediatric kidney recipients, after 2nd dose in 78% and after 3rd dose in 88%. After the 2nd vaccine dose absence of humoral immune response (<33.8 BAU/ml) was only found in case of MMF use (predominately combined with Tac). Peak IgG values (>2080 BAU/ml) were only detected in MMF-free regimens (6/7).
Cell-mediated response partially differed from humoral response, e.g. in some patients SARS-CoV2-Tvis were found despite lack of virus-specific antibodies. After 1st vaccine dose SARS-CoV-2-Tvis were detectable in 50% of pediatric kidney recipients, after 2nd dose in 92%. After 2nd vaccine dose absence or very low levels of SARS-CoV 2-Tvis (<0.3 cells/µl) were only found in Tac-based immunosuppressive regimens, whereas higher levels (>1.3 cells/µl) were exclusively detected in patients with MMF-free medication.
Conclusion: After pediatric kidney transplantation humoral and cellular immune response to SARS-CoV-2 vaccination was suboptimal, but more pronounced than in adult kidney recipients. Use of Tac and MMF was associated with impaired immune response to vaccination. SARS-CoV-2-specific humoral response corresponded only partially to cell-mediated response. Additional monitoring of cellular SARS-CoV-2-specific immunity might be recommendable to improve assessment of the individual vaccine response and thereby to personalize the decision on the necessity of further vaccine doses.