tetano
Editor, Senior Moderator
Sci Transl Med
. 2022 Feb 1;eabl6141.
doi: 10.1126/scitranslmed.abl6141. Online ahead of print.
Infection or a third dose of mRNA vaccine elicit neutralizing antibody responses against SARS-CoV-2 in kidney transplant recipients
Xavier Charmetant[SUP] #[/SUP][SUP] 1 [/SUP], Maxime Espi[SUP] #[/SUP][SUP] 1 [/SUP], Ilies Benotmane[SUP] #[/SUP][SUP] 2 3 4 [/SUP], Véronique Barateau[SUP] 1 [/SUP], Francoise Heibel[SUP] 2 [/SUP], Fanny Buron[SUP] 5 [/SUP], Gabriela Gautier-Vargas[SUP] 2 [/SUP], Marion Delafosse[SUP] 5 [/SUP], Peggy Perrin[SUP] 2 [/SUP], Alice Koenig[SUP] 1 5 6 [/SUP], Noëlle Cognard[SUP] 2 [/SUP], Charlène Levi[SUP] 5 [/SUP], Floriane Gallais[SUP] 3 4 [/SUP], Louis Manière[SUP] 5 [/SUP], Paola Rossolillo[SUP] 7 [/SUP], Eric Soulier[SUP] 4 [/SUP], Florian Pierre[SUP] 4 [/SUP], Anne Ovize[SUP] 8 [/SUP], Emmanuel Morelon[SUP] 1 5 6 [/SUP], Thierry Defrance[SUP] 1 [/SUP], Samira Fafi-Kremer[SUP] 3 4 [/SUP], Sophie Caillard[SUP] #[/SUP][SUP] 2 3 4 [/SUP], Olivier Thaunat[SUP] #[/SUP][SUP] 1 5 6 [/SUP]
Affiliations
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) 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 upon 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. Finally, 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.
. 2022 Feb 1;eabl6141.
doi: 10.1126/scitranslmed.abl6141. Online ahead of print.
Infection or a third dose of mRNA vaccine elicit neutralizing antibody responses against SARS-CoV-2 in kidney transplant recipients
Xavier Charmetant[SUP] #[/SUP][SUP] 1 [/SUP], Maxime Espi[SUP] #[/SUP][SUP] 1 [/SUP], Ilies Benotmane[SUP] #[/SUP][SUP] 2 3 4 [/SUP], Véronique Barateau[SUP] 1 [/SUP], Francoise Heibel[SUP] 2 [/SUP], Fanny Buron[SUP] 5 [/SUP], Gabriela Gautier-Vargas[SUP] 2 [/SUP], Marion Delafosse[SUP] 5 [/SUP], Peggy Perrin[SUP] 2 [/SUP], Alice Koenig[SUP] 1 5 6 [/SUP], Noëlle Cognard[SUP] 2 [/SUP], Charlène Levi[SUP] 5 [/SUP], Floriane Gallais[SUP] 3 4 [/SUP], Louis Manière[SUP] 5 [/SUP], Paola Rossolillo[SUP] 7 [/SUP], Eric Soulier[SUP] 4 [/SUP], Florian Pierre[SUP] 4 [/SUP], Anne Ovize[SUP] 8 [/SUP], Emmanuel Morelon[SUP] 1 5 6 [/SUP], Thierry Defrance[SUP] 1 [/SUP], Samira Fafi-Kremer[SUP] 3 4 [/SUP], Sophie Caillard[SUP] #[/SUP][SUP] 2 3 4 [/SUP], Olivier Thaunat[SUP] #[/SUP][SUP] 1 5 6 [/SUP]
Affiliations
- PMID: 35103481
- DOI: 10.1126/scitranslmed.abl6141
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) 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 upon 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. Finally, 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.