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

Xavier Charmetant , Maxime Espi , Ilies Benotmane (1) , Véronique Barateau , Francoise Heibel , Fanny Buron , Gabriela Gautier-Vargas , Marion Delafosse , Peggy Perrin (1) , Alice Koenig , Noëlle Cognard , Charlène Levi , Floriane Gallais , Louis Manière , Paola Rossolillo (2, 3) , Eric Soulier , Florian Pierre (4, 5) , Anne Ovize , Emmanuel Morelon , Thierry Defrance , Samira Fafi-Kremer (1) , Sophie Caillard (1) , Olivier Thaunat

1 IRM - Immuno-Rhumatologie Moléculaire
2 IGBMC - Institut de Génétique et de Biologie Moléculaire et Cellulaire
3 IGBMC - Institut de génétique et biologie moléculaire et cellulaire
4 ARN - Architecture et Réactivité de l'ARN
5 ARN - Architecture et réactivité de l'ARN

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.

Domaines: Médecine humaine et pathologie

Xavier Charmetant, Maxime Espi, Ilies Benotmane, Véronique Barateau, Francoise Heibel, et al.. Infection or a third dose of mRNA vaccine elicits neutralizing antibody responses against SARS-CoV-2 in kidney transplant recipients. Science Translational Medicine, 2022, 14 (636), ⟨10.1126/scitranslmed.abl6141⟩. ⟨hal-04222054⟩