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Replacing Mycophenolate Mofetil by Everolimus in Kidney Transplant Recipients to Increase Vaccine Immunogenicity:
A Lianne Messchendorp1,2, Luca M Zaeck3, Pim Bouwmans4,5
1Division of Nephrology, Department of Internal Medicine, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Background:
Vaccine immunogenicity is reduced in kidney transplant recipients (KTRs), especially in those using mycophenolate mofetil (MMF). Whether replacement of MMF by everolimus improves vaccine immunogenicity is unknown.
Methods:
KTRs were randomized 1:1 to continue MMF or switch to everolimus. Participants received one coronavirus disease 2019 (COVID-19) booster vaccination and two herpes zoster (HZ) vaccinations at 6, 10 and 14 weeks postrandomization. Primary outcome was the neutralizing antibody response 28 days after COVID-19 vaccination. Secondary outcomes included antibody and T-cell responses 28 days after COVID-19 and HZ vaccination, and safety.
Results:
In 110 KTRs, COVID-19 vaccination resulted in comparable Omicron XBB.1.5 neutralizing antibody titers in the everolimus versus MMF group (308 [74.4-1314] vs 327 [115-897]; P = .83), whereas severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) Spike-specific T-cell responses were slightly lower with everolimus (118 [32.1-243] vs 228 [113-381] spot-forming cells [SFCs]/106 peripheral blood mononuclear cells [PBMCs]; P = .02). HZ vaccination led to higher varicella zoster virus (VZV) glycoprotein E (gE)-specific immunoglobulin G titers with everolimus (2192 [888-4523] vs 1101 [440-2078] 50% endpoint titer; P = .004), while VZV gE-specific T-cell responses were similar (85.0 [27.5-155] vs 115 [50.0-258] SFCs/106 PBMCs; P = .24). Besides known side effects, everolimus led to more bacterial infections (27.3% vs 11.1%; P = .03).
Conclusions:
Six weeks' replacement of MMF by everolimus in KTRs does not improve COVID-19 booster vaccine immunogenicity, whereas 10 weeks' replacement enhances humoral HZ vaccine immunogenicity. While replacing MMF by everolimus may improve vaccine responses, its timing and potential risks require careful consideration.
Insights
Replacing mycophenolate mofetil with everolimus in kidney transplant recipients did not improve COVID-19 vaccine response but enhanced herpes zoster vaccine immunity. Timing of immunosuppressant switch is crucial for optimizing vaccine efficacy and safety.
Area of Science:
- Immunology
- Transplantation
- Vaccinology
Background:
- Kidney transplant recipients (KTRs) exhibit reduced vaccine immunogenicity, particularly those on mycophenolate mofetil (MMF).
- The impact of switching from MMF to everolimus on vaccine response in KTRs remains unclear.
Purpose of the Study:
- To investigate whether replacing MMF with everolimus improves vaccine immunogenicity in KTRs.
- To assess the effects of MMF to everolimus switch on COVID-19 and herpes zoster (HZ) vaccine responses.
Main Methods:
- Randomized controlled trial comparing MMF continuation versus everolimus switch in KTRs.
- Participants received COVID-19 booster and two HZ vaccinations; immune responses (antibody and T-cell) were measured post-vaccination.
Main Results:
- Everolimus did not improve neutralizing antibody titers against COVID-19 Omicron XBB.1.5 compared to MMF.
- Higher immunoglobulin G titers against VZV glycoprotein E were observed after HZ vaccination in the everolimus group.
- T-cell responses to both vaccines were comparable or lower with everolimus, which was also associated with increased bacterial infections.
Conclusions:
- Switching from MMF to everolimus does not enhance COVID-19 booster immunogenicity in KTRs.
- A 10-week MMF to everolimus switch may improve humoral immunity for HZ vaccines.
- The timing and potential risks associated with MMF to everolimus conversion require careful consideration for vaccine response optimization.
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