Immune response to third SARS-CoV-2 vaccination in seronegative kidney transplant recipients: possible improvement by mycophenolate mofetil reduction

Background Modification of vaccination strategies is needed to improve the immune response to SARS-CoV-2 vaccination in kidney transplant recipients (KTRs). Methods This multicenter observational study aimed to determine antibody kinetics among 60 seropositive KTRs and analyzed the effects of the third vaccination against SARS-CoV-2 in 174 previously seronegative KTRs. We investigated whether mycophenolate mofetil (MMF) dose reduction by 25-50% prior the third vaccination influences vaccination success. Results 18 of 60 (30%) seropositive KTRs became seronegative in the serological assay within six months. Loss of antibodies was predicted by low initial antibody levels (≤206.8 BAU/ml), older age, and impaired graft function. A third vaccination in previously seronegative KTRs induced seroconversion in 56 of 174 (32.1%) KTRs with median antibody levels 119 (76–353) BAU/ml and median neutralizing capacity titer of 1:10 (0– 1:40). Multivariate logistic regression revealed that initial antibody levels (OR 1.39, 95% CI 1.09–1.76), graft function (OR 0.05, 95% CI 0.01–0.39), time after transplantation (OR 1.04, 95% CI 1.02–1.07) and MMF trough levels (OR 0.43, 95% CI 0.21–0.88) correlated with seroconversion, p<0.05. After controlling for these confounders, the effect of MMF dose reduction was calculated using propensity score matching. KTRs in the MMF reduction group had significantly lower MMF serum concentrations prior to the third vaccination and were more likely to develop antibody levels ≥35.2 BAU/ml than their matched KTRs (p=0.02). Conclusions Temporary reduction in MMF dose might be a promising approach to improve the immune response in KTRs.