Infection or a third dose of mRNA vaccine elicits neutralizing antibody responses against SARS-CoV-2 in kidney transplant recipients

Author:

Charmetant Xavier1ORCID,Espi Maxime1ORCID,Benotmane Ilies234ORCID,Barateau Véronique1,Heibel Francoise2,Buron Fanny5ORCID,Gautier-Vargas Gabriela2ORCID,Delafosse Marion5,Perrin Peggy2ORCID,Koenig Alice156,Cognard Noëlle2ORCID,Levi Charlène5ORCID,Gallais Floriane34ORCID,Manière Louis5,Rossolillo Paola7,Soulier Eric4ORCID,Pierre Florian4ORCID,Ovize Anne8,Morelon Emmanuel156,Defrance Thierry1ORCID,Fafi-Kremer Samira34,Caillard Sophie234ORCID,Thaunat Olivier156ORCID

Affiliation:

1. CIRI, INSERM U1111, Université Claude Bernard Lyon I, CNRS UMR5308, Ecole Normale Supérieure de Lyon, Univ. Lyon, 21 avenue Tony Garnier, 69007 Lyon, France.

2. Department of Nephrology and Transplantation, Strasbourg University Hospital, 67000 Strasbourg, France.

3. Department of Virology, Strasbourg University Hospital, 67000 Strasbourg, France.

4. Inserm UMR S1109, LabEx Transplantex, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg, 67000 Strasbourg, France.

5. Department of Transplantation, Nephrology, and Clinical Immunology, Hospices Civils de Lyon, Edouard Herriot Hospital, 5, place d’Arsonval, 69003 Lyon, France.

6. Claude Bernard University (Lyon 1), 43 boulevard du 11 Novembre 1918, 69622 Villeurbanne, France.

7. Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Centre National de la Recherche Scientifique (CNRS), UMR 7104, Institut National de la Santé et de la Recherche Médicale (INSERM), U1258, Université de Strasbourg, 67400 Illkirch, France.

8. Eurofins Biomnis Laboratory, 69007 Lyon, France.

Abstract

Transplant recipients, who receive therapeutic immunosuppression to prevent graft rejection, are characterized by high coronavirus disease 2019 (COVID-19)–related mortality and defective response to vaccines. We observed that previous infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but not the standard two-dose regimen of vaccination, provided protection against symptomatic COVID-19 in kidney transplant recipients. We therefore compared the cellular and humoral immune responses of these two groups of patients. Neutralizing anti–receptor-binding domain (RBD) immunoglobulin G (IgG) antibodies were identified as the primary correlate of protection for transplant recipients. Analysis of virus-specific B and T cell responses suggested that the generation of neutralizing anti-RBD IgG may have depended on cognate T-B cell interactions that took place in germinal center, potentially acting as a limiting checkpoint. High-dose mycophenolate mofetil, an immunosuppressive drug, was associated with fewer antigen-specific B and T follicular helper (TFH) cells after vaccination; this was not observed in patients recently infected with SARS-CoV-2. Last, we observed that, in two independent prospective cohorts, administration of a third dose of SARS-CoV-2 mRNA vaccine restored neutralizing titers of anti-RBD IgG in about 40% of individuals who had not previously responded to two doses of vaccine. Together, these findings suggest that a third dose of SARS-CoV-2 mRNA vaccine improves the RBD-specific responses of transplant patients treated with immunosuppressive drugs.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

General Medicine

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