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Comparison of infected and vaccinated transplant recipients highlights the role of Tfh and neutralizing IgG in COVID-19 protection
Xavier Charmetant; Maxime ESPI; Ilies Benotmane; Francoise Heibel; Fanny Buron; Gabriela Gautier-Vargas; Marion Delafosse; Peggy Perrin; Alice Koenig; Noelle Cognard; Charlene Levi; Floriane Gallais; Louis Maniere; Paola Rossolillo; Eric Soulier; Florian Pierre; Anne Ovize; Emmanuel Morelon; Thierry Defrance; Samira Fafi-Kremer; Sophie Caillard; Olivier Thaunat.
  • Xavier Charmetant; CIRI, INSERM U1111, Universite Claude Bernard Lyon I, CNRS UMR5308, Ecole Normale Superieure de Lyon, Univ. Lyon, 21 avenue Tony Garnier, 69007 Lyon, France.
  • Maxime ESPI; INSERM CIRI U1111, Lyon
  • Ilies Benotmane; Department of Nephrology and Transplantation, Strasbourg University Hospital, Strasbourg, France
  • Francoise Heibel; Department of Nephrology and Transplantation, Strasbourg University Hospital, Strasbourg, France
  • Fanny Buron; Hospices Civils de Lyon, Edouard Herriot Hospital, Department of Transplantation, Nephrology and Clinical Immunology, Lyon, France
  • Gabriela Gautier-Vargas; Department of Nephrology and Transplantation, Strasbourg University Hospital, Strasbourg, France
  • Marion Delafosse; Hospices Civils de Lyon, Edouard Herriot Hospital, Department of Transplantation, Nephrology and Clinical Immunology, Lyon, France
  • Peggy Perrin; Department of Nephrology and Transplantation, Strasbourg University Hospital, Strasbourg, France
  • Alice Koenig; CIRI, INSERM U1111, Universite Claude Bernard Lyon I, CNRS UMR5308, Ecole Normale Superieure de Lyon, Univ. Lyon, 21 avenue Tony Garnier, 69007 Lyon, France
  • Noelle Cognard; Department of Nephrology and Transplantation, Strasbourg University Hospital, Strasbourg, France
  • Charlene Levi; Hospices Civils de Lyon, Edouard Herriot Hospital, Department of Transplantation, Nephrology and Clinical Immunology, Lyon, France
  • Floriane Gallais; Department of Virology, Strasbourg University Hospital, Strasbourg, France
  • Louis Maniere; Hospices Civils de Lyon, Edouard Herriot Hospital, Department of Transplantation, Nephrology and Clinical Immunology, Lyon, France
  • Paola Rossolillo; Institut de Genetique et de Biologie Moleculaire et Cellulaire (IGBMC), Centre National de la Recherche Scientifique (CNRS), UMR 7104, Institut National de la S
  • Eric Soulier; Inserm UMR S1109, LabEx Transplantex, Federation de Medecine Translationnelle de Strasbourg (FMTS), Universite de Strasbourg, Strasbourg, France
  • Florian Pierre; Inserm UMR S1109, LabEx Transplantex, Federation de Medecine Translationnelle de Strasbourg (FMTS), Universite de Strasbourg, Strasbourg, France
  • Anne Ovize; Eurofins Biomnis Laboratory, 69007 Lyon, France
  • Emmanuel Morelon; Hospices Civils de Lyon, Edouard Herriot Hospital, Department of Transplantation, Nephrology and Clinical Immunology, Lyon, France. Claude Bernard University (L
  • Thierry Defrance; CIRI, INSERM U1111, Universite Claude Bernard Lyon I, CNRS UMR5308, Ecole Normale Superieure de Lyon, Univ. Lyon, 21 avenue Tony Garnier, 69007 Lyon, France
  • Samira Fafi-Kremer; Department of Virology, Strasbourg University Hospital, Strasbourg, France. Inserm UMR S1109, LabEx Transplantex, Federation de Medecine Translationnelle de Str
  • Sophie Caillard; Department of Nephrology and Transplantation, Strasbourg University Hospital, Strasbourg, France. Inserm UMR S1109, LabEx Transplantex, Federation de Medecine T
  • Olivier Thaunat; CIRI, INSERM U1111, Universite Claude Bernard Lyon I, CNRS UMR5308, Ecole Normale Superieure de Lyon, Lyon, France. 5Hospices Civils de Lyon, Edouard Herriot Ho
Preprint Dans Anglais | medRxiv | ID: ppmedrxiv-21260852
ABSTRACT
Transplant recipients, which receive therapeutic immunosuppression to prevent graft rejection, are characterized by high COVID-19-related mortality and defective response to vaccines. Having observed that previous infection by SARS-CoV-2 but not the standard "2 doses" scheme of vaccination, provided complete protection against COVID-19 to transplant recipients, we undertook this translational study to compare the cellular and humoral immune responses of these 2 groups of patients. Neutralizing anti-Receptor Binding Domain (RBD) IgG were identified as the critical immune effectors associated with protection. Generation of anti-RBD IgG was dependent upon spike-specific T follicular helper (Tfh) CD4+ T cells, which acted as limiting checkpoint. Tfh generation was impeded by high dose mycophenolate mofetil in non-responders to vaccine but not in infected patients, suggesting that increasing immunogenicity of vaccine could improve response rate to mRNA vaccine. This theory was validated in two independent prospective cohorts, in which administration of a 3rd dose of vaccine resulted in the generation of anti-RBD IgG in half of non-responders to 2 doses. One sentence summaryThe generation of neutralizing IgG, which protects kidney transplant recipients from COVID-19, requires T follicular helper cells.
Texte intégral: Disponible Collection: Preprints Base de données: medRxiv Type d'étude: Essai contrôlé randomisé Les sujets: Vaccins langue: Anglais Année: 2021 Type de document: Preprint

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Texte intégral: Disponible Collection: Preprints Base de données: medRxiv Type d'étude: Essai contrôlé randomisé Les sujets: Vaccins langue: Anglais Année: 2021 Type de document: Preprint