Emily
Editor, Senior Moderator
https://www.medrxiv.org/content/10.1101/2021.07.22.21260852v1
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 Manière, Paola Rossolillo, Eric Soulier, Florian Pierre, Anne Ovize, Emmanuel Morelon, Thierry Defrance, Samira Fafi-Kremer, Sophie Caillard, Olivier Thaunat
medRxiv 2021.07.22.21260852; doi: https://doi.org/10.1101/2021.07.22.21260852 This article is a preprint and has not been peer-reviewed [what does this mean?]. It reports new medical research that has yet to be evaluated and so should not be used to guide clinical practice.
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 3[SUP]rd[/SUP] dose of vaccine resulted in the generation of anti-RBD IgG in half of non-responders to 2 doses.
One sentence summary The generation of neutralizing IgG, which protects kidney transplant recipients from COVID-19, requires T follicular helper cells.
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 Manière, Paola Rossolillo, Eric Soulier, Florian Pierre, Anne Ovize, Emmanuel Morelon, Thierry Defrance, Samira Fafi-Kremer, Sophie Caillard, Olivier Thaunat
medRxiv 2021.07.22.21260852; doi: https://doi.org/10.1101/2021.07.22.21260852 This article is a preprint and has not been peer-reviewed [what does this mean?]. It reports new medical research that has yet to be evaluated and so should not be used to guide clinical practice.
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 3[SUP]rd[/SUP] dose of vaccine resulted in the generation of anti-RBD IgG in half of non-responders to 2 doses.
One sentence summary The generation of neutralizing IgG, which protects kidney transplant recipients from COVID-19, requires T follicular helper cells.