Intensity of mycophenolate mofetil treatment is associated with an impaired immune response to SARS-CoV-2 vaccination in kidney transplant recipients

Abstract

Kidney transplant recipients (KTRs) are extremely vulnerable to SARS-CoV-2 infection and show an impaired immune response to SARS-CoV-2 vaccination. We analyzed factors related to vaccination efficiency in KTRs. In a multicenter prospective observational study (NCT04743947), IgG antibodies levels against SARS-CoV-2 spike S1 subunit and their neutralization capacity after SARS-CoV-2 vaccination were analyzed in 225 KTRs and compared to 176 controls. After the vaccination, 56 (24.9%) KTRs became seropositive of whom 68% had neutralizing antibodies. This immune response was significantly lower compared to controls (239 [78-519] BAU/ml versus 1826 [560-3180] BAU/ml for KTRs and controls, p < .0001). The strongest predictor for an impaired response was mycophenolate mofetil (MMF) treatment. Multivariate regression analysis revealed that MMF-free regimen was highly associated with seroconversion (OR 13.25, 95% CI 3.22-54.6; p < .001). In contrast, other immunosuppressive drugs had no significant influence. 187 out of 225 KTRs were treated with MMF of whom 26 (13.9%) developed antibodies. 23 of these seropositive KTRs had a daily MMF dose ≤1 g. Furthermore, higher trough MMF concentrations correlated with lower antibody titers (R -0.354, p < .001) supporting a dose-dependent unfavorable effect of MMF. Our data indicate that MMF dose modification could lead to an improved immune response.

Keywords: clinical research/practice; immunosuppression/immune modulation; immunosuppressive regimens; infection and infectious agents - viral; kidney transplantation/nephrology; vaccine.

FIGURE 1

Immune response to SARS-CoV-2 vaccination in kidney transplant recipients. (A) Comparison of antibody titers against Sars-CoV-2 spike S1 subunit between controls and KTRs. Dashed line was set at 35.2 BAU/ml to outline seropositive patients. (B) Comparison of neutralizing antibody capacity between seropositive controls and KTRs. (C) Association between anti-SARS-CoV-2 antibodies and neutralizing antibody titers in seropositive KTRs. (D) Development of antibody titer between different MMF regime groups. Patients who developed measurable antibody levels were only included. Dashed line was set to outline seropositive patients. (E) Correlation between MMF concentration in the blood and development of IgG antibodies (R −0.354, p < .001). Differences were assessed using Mann-Whitney test or Kruskal-Wallis test were applicable. ****Represent p value < .0001, ***p < .001, **p < .01, *p < .05.