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- Title
Infection or a third dose of mRNA vaccine elicits neutralizing antibody responses against SARS-CoV-2 in kidney transplant recipients.
- Authors
Charmetant, Xavier; Espi, Maxime; Benotmane, Ilies; Barateau, Véronique; Heibel, Francoise; Buron, Fanny; Gautier-Vargas, Gabriela; Delafosse, Marion; Perrin, Peggy; Koenig, Alice; Cognard, Noëlle; Levi, Charlène; Gallais, Floriane; Manière, Louis; Rossolillo, Paola; Soulier, Eric; Pierre, Florian; Ovize, Anne; Morelon, Emmanuel; Defrance, Thierry
- 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. Protecting transplant recipients: Recipients of kidney transplants are placed on immunosuppressive drugs, which, while prevent rejection of their graft, also put them at increased risk of infections with viruses such as SARS-CoV-2. Here, the authors compared the immune response elicited by SARS-CoV-2 infection and vaccination in kidney transplant recipients. Infection elicited a broader response to SARS-CoV-2 associated with fewer cases of reinfection. The authors also observed a subset of individuals that did not respond to two doses of mRNA vaccine, potentially due to exposure to the immunosuppressive drug, mycophenolate mofetil. A subset of nonresponders who received a third dose of mRNA vaccine developed antibodies comparable to responders to two doses, suggesting that populations with immunosuppression should be prioritized for booster vaccine doses.
- Subjects
COVID-19; T helper cells; KIDNEY transplantation; BASILIXIMAB; ANTIBODY formation; SARS-CoV-2
- Publication
Science Translational Medicine, 2022, Vol 14, Issue 636, p1
- ISSN
1946-6234
- Publication type
Article
- DOI
10.1126/scitranslmed.abl6141