[en] [en] INTRODUCTION: Comorbidities and immunosuppressive therapies are associated with reduced immune responses to primary COVID-19 mRNA vaccination in kidney transplant recipients (KTRs). In healthy individuals, prior SARS-COV-2 infection is associated with increased vaccine responses, a phenotype called hybrid immunity. In this study, we explored the potential influence of immune suppression on hybrid immunity in KTRs.
METHODS: Eighty-two KTRs, including 59 SARS-CoV-2-naïve (naïve KTRs [N-KTRs]) and 23 SARS-CoV-2-experienced (experienced KTRs [E-KTRs]) patients, were prospectively studied and compared to 106 healthy controls (HCs), including 40 SARS-CoV-2-naïve (N-HCs) and 66 SARS-CoV-2-experienced (E-HCs) subjects. Polyfunctional antibody and T cell responses were measured following 2 doses of BNT162b2 mRNA vaccine. Associations between vaccine responses and clinical characteristics were studied by univariate and multivariate analyses.
RESULTS: In naïve KTRs, vaccine responses were markedly lower than in HCs and were correlated with older age, more recent transplantation, kidney retransplantation after graft failure, arterial hypertension, and treatment with mycophenolate mofetil (MMF). In contrast, vaccine responses of E-KTRs were similar to those of HCs and were associated with time between transplantation and vaccination, but not with the other risk factors associated with low vaccine responses in naïve KTRs.
CONCLUSION: In conclusion, hybrid immunity overcomes immune suppression and provides potent humoral and cellular immunity to SARS-CoV-2 in KTRs.
Disciplines :
Immunology & infectious disease
Author, co-author :
Gemander, Nicolas; Institute for Medical Immunology and Université Libre de Bruxelles Centre for Research in Immunology, Université Libre de Bruxelles, Gosselies, Belgium
Kemlin, Delphine; Institute for Medical Immunology and Université Libre de Bruxelles Centre for Research in Immunology, Université Libre de Bruxelles, Gosselies, Belgium ; Department of Nephrology, Dialysis and Transplantation, Erasme Hospital, Université Libre de Bruxelles, Brussels, Belgium
Depickère, Stéphanie; Clinical Trial Unit, Scientific Direction Infectious Diseases in Humans, Sciensano, Brussels, Belgium
Kelkar, Natasha S; Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Dartmouth College, Hanover, New Hampshire, USA
Pannus, Pieter; Institute for Medical Immunology and Université Libre de Bruxelles Centre for Research in Immunology, Université Libre de Bruxelles, Gosselies, Belgium
Sharma, Shilpee; Institute for Medical Immunology and Université Libre de Bruxelles Centre for Research in Immunology, Université Libre de Bruxelles, Gosselies, Belgium
Waegemans, Alexandra; Institute for Medical Immunology and Université Libre de Bruxelles Centre for Research in Immunology, Université Libre de Bruxelles, Gosselies, Belgium
Olislagers, Véronique; Institute for Medical Immunology and Université Libre de Bruxelles Centre for Research in Immunology, Université Libre de Bruxelles, Gosselies, Belgium
Georges, Daphnée ; Université de Liège - ULiège > Integrative Biological Sciences (InBioS) ; Institute for Medical Immunology and Université Libre de Bruxelles Centre for Research in Immunology, Université Libre de Bruxelles, Gosselies, Belgium
Dhondt, Emilie; Virology Unit, Department of Biomedical Sciences, Institute of Tropical Medicine, Antwerp, Belgium
Braga, Margarida; Virology Unit, Department of Biomedical Sciences, Institute of Tropical Medicine, Antwerp, Belgium
Heyndrickx, Leo; Virology Unit, Department of Biomedical Sciences, Institute of Tropical Medicine, Antwerp, Belgium
Michiels, Johan; Virology Unit, Department of Biomedical Sciences, Institute of Tropical Medicine, Antwerp, Belgium
Thiriard, Anaïs; Institute for Medical Immunology and Université Libre de Bruxelles Centre for Research in Immunology, Université Libre de Bruxelles, Gosselies, Belgium
Lemy, Anne; Department of Nephrology, Marie Curie Hospital, Charleroi, Belgium
Goossens, Maria E; Clinical Trial Unit, Scientific Direction Infectious Diseases in Humans, Sciensano, Brussels, Belgium
Matagne, André ; Université de Liège - ULiège > Département des sciences de la vie > Enzymologie et repliement des protéines
Desombere, Isabelle; Laboratory of Immune Response, Scientific Direction Infectious Diseases in Humans, Sciensano, Brussels, Belgium
Ariën, Kevin K; Virology Unit, Department of Biomedical Sciences, Institute of Tropical Medicine, Antwerp, Belgium ; Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium
Ackerman, Margaret E; Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Dartmouth College, Hanover, New Hampshire, USA ; Thayer School of Engineering, Dartmouth College, Hanover, New Hampshire, USA
Le Moine, Alain; Institute for Medical Immunology and Université Libre de Bruxelles Centre for Research in Immunology, Université Libre de Bruxelles, Gosselies, Belgium ; Department of Nephrology, Dialysis and Transplantation, Erasme Hospital, Université Libre de Bruxelles, Brussels, Belgium
Marchant, Arnaud; Institute for Medical Immunology and Université Libre de Bruxelles Centre for Research in Immunology, Université Libre de Bruxelles, Gosselies, Belgium
The authors thank all patients for their generous participation in the study. The authors thank Sorya Fagnoul and Emilie Navaux for their help in the recruitment of patients. Maria Spanu and Anne Gillardin for the sampling and the follow-up of patients. Inès Vu Duc, Fatima Gjemajli, Sara Cuman, Robin Van Naemen, Florian Ballieu, Vianney Nana Tchouta, Marie-Annick Ottou Eyenga, and Caroline Rodeghiero for technical assistance. The authors thank the Robotein platform of the BE Instruct-ERIC Centre for providing access to the Octet HTX and the Microlab STAR liquid handling workstation. Graphical abstract was created withBioRender.com. This study was cofunded by the Belgian Federal Government through Sciensano, Belgium, by the Fonds de la Recherche Scientifique, F.R.S.-FNRS, Belgium, and by the Fonds Erasme, Belgium. NG received a PhD studentship from the Fonds Erasme and F.R.S- FNRS. DK received a PhD studentship from the F.R.S- FNRS. AM is Research Director of the F.R.S.-FNRS. This study was supported in part by the US NIAID (grants R56AI165448 and P01AI162242). The datasets used and analyzed during the current study are available from the corresponding author on reasonable request, following material transfer agreement. NG, DK, ALM, and AM conceptualized the study. DK and PP wrote the clinical study protocol. DK obtained permission from the ethics committee and A.F.M.P.S. MEG, ALM, and AM secured the funding of the study. NG, DK and AL conducted the clinical study. ALM overviewed the clinical study. NG, DK, SS, AW, VO, DG, ED, MB, LH, JM, and MV conducted the laboratory analyses. PP, SS, AT, AMat, ID, KKA, MEA, and AM overviewed the laboratory analyses. NG, DK, SD, NK, DG, and LH contributed to data analysis and interpretation. NG, DK, SD, MEA, and AM interpreted the data. NG, PP, and AM drafted the manuscript. All coauthors reviewed, edited, and approved the manuscript.
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