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

Abstract

Modification of vaccination strategies is necessary to improve the immune response to SARS‐CoV‐2 vaccination in kidney transplant recipients (KTRs). This multicenter observational study analyzed the effects of the third SARS‐CoV‐2 vaccination in previously seronegative KTRs with the focus on temporary mycophenolate mofetil (MMF) dose reduction within propensity matched KTRs. 56 out of 174 (32%) previously seronegative KTRs became seropositive after the third vaccination with only three KTRs developing neutralizing antibodies against the omicron variant. Multivariate logistic regression revealed that initial antibody levels, graft function, time after transplantation and MMF trough levels had an influence on seroconversion ( P < .05). After controlling for confounders, the effect of MMF dose reduction before the third vaccination was calculated using propensity score matching. KTRs with a dose reduction of ≥33% showed a significant decrease in MMF trough levels to 1.8 (1.2–2.5) μg/ml and were more likely to seroconvert than matched controls ( P = .02). Therefore, a MMF dose reduction of 33% or more before vaccination is a promising approach to improve success of SARS‐CoV‐2 vaccination in KTRs.

Immune Response to COVID-19 mRNA Vaccination in Previous Nonresponder Kidney Transplant Recipients After Short-term Withdrawal of Mycophenolic Acid 1 and 3 Months After an Additional Vaccine Dose

“…Nonetheless, the de novo DSA formation and increases in the MFI of preexisting DSA at both t1 and t2 suggest an association between MPA withdrawal and enhanced alloimmune response. Considering possible options to enhance patients’ safety for future approaches of MPA withdrawal for immunocompromised nonresponders, Kantauskaite et al 12 have shown that an MPA dosage reduction by 25% to 50% before a third vaccination led to an enhanced immune response in 24 KTRs. Regele et al, 34 on the other hand, showed that a shorter MPA withdrawal period 2 wk perivaccination failed to enhance vaccine responsiveness.…”

“…Accordingly, several studies have analyzed the effects of an additional COVID-19 vaccination during short-term MPA withdrawal (4–6 wk) and have demonstrated significantly higher seroconversion rates than patients on continued immunosuppressive maintenance therapy. 9-12…”

Humoral Immune Response to a Timely Booster mRNA Vaccination in Non-Responders to a Standard Vaccination Schedule against COVID-19 in Kidney Transplant Recipients

“…Accordingly, we did not find a statistically significant association between the type of immunosuppressive treatment and non-response. Nevertheless, significant correlation with seroconversion in kidney transplant recipients who discontinued treatment with an antimetabolite prior to a third vaccination had been observed [ 28 , 30 , 31 ]. Osmanodja et al found that younger age, higher BMI, higher transplant age, higher eGFR, and higher hemoglobin levels were associated with improved serological response after a third vaccination [ 32 ].…”

Efficacy and safety of booster vaccination against SARS-CoV-2 in dialysis and renal transplant patients: systematic review and meta-analysis

“…Yet attempts have been made to provide an overview. In case of baseline serum creatinine levels, except for one study [ 17 ], all other reports indicated trends of lower serum creatinine values in seroresponders than in non-responders [ 53 , 58 , 61 ], with some of them reaching significance [ 18 , 21 , 60 ]. Vintage on RRT, however, tended to be longer in responders in all [ 17 , 21 , 32 , 53 , 61 ], but one [ 13 ] study.…”