Replacing Mycophenolate Mofetil by Everolimus in Kidney Transplant Recipients to Increase Vaccine Immunogenicity : Results of a Randomized Controlled Trial
(2025) In Clinical Infectious Diseases- Abstract
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... (More)
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.
(Less)
- author
- Lianne Messchendorp, A.
; Zaeck, Luca M.
; Bouwmans, Pim
; van den Broek, Dennis A.J.
; Frölke, Sophie C.
; Geers, Daryl
; Imhof, Céline
; Malahe, Reshwan S.K.
; Schmitz, Katharina S.
; Reinders, Julian
; Visscher, Frederique E.
; Baan, Carla C.
; Bemelman, Frederike J.
; Gansevoort, Ron T.
; GeurtsvanKessel, Corine H.
; Hemmelder, Marc H.
; Hilbrands, Luuk B.
; Källmark, Hanna
LU
; Kapetanovic, Meliha C.
LU
; Kho, Marcia M.L.
; de Vries, Aiko P.J.
; van Zuilen, Arjan D.
; Reinders, Marlies E.
; van Baarle, Debbie
; de Vries, Rory D.
; Sanders, Jan Stephan F.
; Abrahams, Alferso C.
; Dolmans, Helma
; Adema, Yvonne M.R.
; Ahoud, Sandra
; Becker, Monique
; Eggenhuizen, Esther
; Huizenga, Xanne
; van Berkel, Sonja
; van Deursen, Nelleke
; Boer-Verschragen, Marieken J.
; van der Hurk, Chantal
; Bogers, Susanne
; Hollander-Alblas, Kimerley
; Wijnans, Koen
; ten Dam, Marc A.G.J.
; van der Heiden, Marieke
; Mullens, Monique
; Noorlander, Joëlle
; Standaar, Dorien
; Stijman-Moerman, Irma
and Vervoort, Hanneke
(Less) - author collaboration
- organization
- publishing date
- 2025
- type
- Contribution to journal
- publication status
- epub
- subject
- keywords
- immunosuppressive agents, randomized controlled trial, solid organ transplant recipients, vaccine immunogenicity
- in
- Clinical Infectious Diseases
- article number
- ciaf107
- publisher
- Oxford University Press
- external identifiers
-
- pmid:40231961
- scopus:105018958050
- ISSN
- 1058-4838
- DOI
- 10.1093/cid/ciaf107
- language
- English
- LU publication?
- yes
- additional info
- Publisher Copyright: © The Author(s) 2025.
- id
- 6b37e5a9-42b4-4276-9530-53a0c57be14b
- date added to LUP
- 2026-01-22 11:29:03
- date last changed
- 2026-01-23 10:44:12
@article{6b37e5a9-42b4-4276-9530-53a0c57be14b,
abstract = {{<p>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]/10<sup>6</sup> 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/10<sup>6</sup> 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.</p>}},
author = {{Lianne Messchendorp, A. and Zaeck, Luca M. and Bouwmans, Pim and van den Broek, Dennis A.J. and Frölke, Sophie C. and Geers, Daryl and Imhof, Céline and Malahe, Reshwan S.K. and Schmitz, Katharina S. and Reinders, Julian and Visscher, Frederique E. and Baan, Carla C. and Bemelman, Frederike J. and Gansevoort, Ron T. and GeurtsvanKessel, Corine H. and Hemmelder, Marc H. and Hilbrands, Luuk B. and Källmark, Hanna and Kapetanovic, Meliha C. and Kho, Marcia M.L. and de Vries, Aiko P.J. and van Zuilen, Arjan D. and Reinders, Marlies E. and van Baarle, Debbie and de Vries, Rory D. and Sanders, Jan Stephan F. and Abrahams, Alferso C. and Dolmans, Helma and Adema, Yvonne M.R. and Ahoud, Sandra and Becker, Monique and Eggenhuizen, Esther and Huizenga, Xanne and van Berkel, Sonja and van Deursen, Nelleke and Boer-Verschragen, Marieken J. and van der Hurk, Chantal and Bogers, Susanne and Hollander-Alblas, Kimerley and Wijnans, Koen and ten Dam, Marc A.G.J. and van der Heiden, Marieke and Mullens, Monique and Noorlander, Joëlle and Standaar, Dorien and Stijman-Moerman, Irma and Vervoort, Hanneke}},
issn = {{1058-4838}},
keywords = {{immunosuppressive agents; randomized controlled trial; solid organ transplant recipients; vaccine immunogenicity}},
language = {{eng}},
publisher = {{Oxford University Press}},
series = {{Clinical Infectious Diseases}},
title = {{Replacing Mycophenolate Mofetil by Everolimus in Kidney Transplant Recipients to Increase Vaccine Immunogenicity : Results of a Randomized Controlled Trial}},
url = {{http://dx.doi.org/10.1093/cid/ciaf107}},
doi = {{10.1093/cid/ciaf107}},
year = {{2025}},
}