Hybrid Immunity Overcomes Defective Immune Response to COVID-19 Vaccination in Kidney Transplant Recipients

Nicolas Gemander; Delphine Kemlin; Stéphanie Depickère; Natasha S Kelkar; Pieter Pannus; Shilpee Sharma; Alexandra Waegemans; Véronique Olislagers; Daphnée Georges; Emilie Dhondt; Margarida Braga; Leo Heyndrickx; Johan Michiels; Anaïs Thiriard; Anne Lemy; Marylène Vandevenne; Maria E Goossens; André Matagne; Isabelle Desombere; Kevin K Ariën; Margaret E Ackerman; Alain Le Moine; Arnaud Marchant

doi:10.1016/j.ekir.2023.12.008

Hybrid Immunity Overcomes Defective Immune Response to COVID-19 Vaccination in Kidney Transplant Recipients

Kidney Int Rep. 2023 Dec 20;9(3):635-648. doi: 10.1016/j.ekir.2023.12.008. eCollection 2024 Mar.

Authors

Nicolas Gemander¹, Delphine Kemlin^{1

2}, Stéphanie Depickère³, Natasha S Kelkar⁴, Pieter Pannus¹, Shilpee Sharma¹, Alexandra Waegemans¹, Véronique Olislagers¹, Daphnée Georges^{1

5}, Emilie Dhondt⁶, Margarida Braga⁶, Leo Heyndrickx⁶, Johan Michiels⁶, Anaïs Thiriard¹, Anne Lemy⁷, Marylène Vandevenne⁵, Maria E Goossens³, André Matagne⁵, Isabelle Desombere⁸, Kevin K Ariën^{6

9}, Margaret E Ackerman^{4

10}, Alain Le Moine^{1

2}, Arnaud Marchant¹

Affiliations

¹ Institute for Medical Immunology and Université Libre de Bruxelles Centre for Research in Immunology, Université Libre de Bruxelles, Gosselies, Belgium.
² Department of Nephrology, Dialysis and Transplantation, Erasme Hospital, Université Libre de Bruxelles, Brussels, Belgium.
³ Clinical Trial Unit, Scientific Direction Infectious Diseases in Humans, Sciensano, Brussels, Belgium.
⁴ Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Dartmouth College, Hanover, New Hampshire, USA.
⁵ Laboratory of Enzymology and Protein Folding, Centre for Protein Engineering, InBioS, University of Liège, Liège, Belgium.
⁶ Virology Unit, Department of Biomedical Sciences, Institute of Tropical Medicine, Antwerp, Belgium.
⁷ Department of Nephrology, Marie Curie Hospital, Charleroi, Belgium.
⁸ Laboratory of Immune Response, Scientific Direction Infectious Diseases in Humans, Sciensano, Brussels, Belgium.
⁹ Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium.
¹⁰ Thayer School of Engineering, Dartmouth College, Hanover, New Hampshire, USA.

Abstract

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.

Keywords: COVID-19; hybrid immunity; kidney transplantation; mRNA vaccination; nonneutralizing antibodies; systems immunology.