Antigen-selective modulation of AAV immunogenicity with tolerogenic rapamycin nanoparticles enables successful vector re-administration - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Nature Communications Année : 2018

Antigen-selective modulation of AAV immunogenicity with tolerogenic rapamycin nanoparticles enables successful vector re-administration

Amine Meliani
Florence Boisgerault
  • Fonction : Auteur
Romain Hardet
  • Fonction : Auteur
Solenne Marmier
  • Fonction : Auteur
Fanny Collaud
Giuseppe Ronzitti
Christian Leborgne
Helena Costa Verdera
Marcelo Simon Sola
Severine Charles
  • Fonction : Auteur
Alban Vignaud
  • Fonction : Auteur
Laetitia van Wittenberghe
  • Fonction : Auteur
Giorgia Manni
  • Fonction : Auteur
Olivier Christophe
  • Fonction : Auteur
Francesca Fallarino
Christopher Roy
  • Fonction : Auteur
Alicia Michaud
  • Fonction : Auteur
Petr Ilyinskii
  • Fonction : Auteur
Takashi Kei Kishimoto
  • Fonction : Auteur
Federico Mingozzi

Résumé

Abstract Gene therapy mediated by recombinant adeno-associated virus (AAV) vectors is a promising treatment for systemic monogenic diseases. However, vector immunogenicity represents a major limitation to gene transfer with AAV vectors, particularly for vector re-administration. Here, we demonstrate that synthetic vaccine particles encapsulating rapamycin (SVP[Rapa]), co-administered with AAV vectors, prevents the induction of anti-capsid humoral and cell-mediated responses. This allows successful vector re-administration in mice and nonhuman primates. SVP[Rapa] dosed with AAV vectors reduces B and T cell activation in an antigen-selective manner, inhibits CD8 + T cell infiltration in the liver, and efficiently blocks memory T cell responses. SVP[Rapa] immunomodulatory effects can be transferred from treated to naive mice by adoptive transfer of splenocytes, and is inhibited by depletion of CD25 + T cells, suggesting a role for regulatory T cells. Co-administration of SVP[Rapa] with AAV vector represents a powerful strategy to modulate vector immunogenicity and enable effective vector re-administration.

Dates et versions

hal-04324439 , version 1 (05-12-2023)

Identifiants

Citer

Amine Meliani, Florence Boisgerault, Romain Hardet, Solenne Marmier, Fanny Collaud, et al.. Antigen-selective modulation of AAV immunogenicity with tolerogenic rapamycin nanoparticles enables successful vector re-administration. Nature Communications, 2018, 9 (1), pp.4098. ⟨10.1038/s41467-018-06621-3⟩. ⟨hal-04324439⟩
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