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

Article · Amine Meliani, Florence Boisgérault, Romain Hardet, Solenne Marmier, Fanny Collaud, Giuseppe Ronzitti, Christian Leborgne, Helena Costa Verdera, Marcelo Simon Sola, Séverine Charles, Alban Vignaud, Laetitia van Wittenberghe, Giorgia Manni, Olivier D. Christophe, Francesca Fallarino, Christopher J. Roy, Alicia M. Michaud, Petr O. Ilyinskii, Takashi Kishimoto, Federico Mingozzi

- Archive id: doi:10.1038/s41467-018-06621-3
- Published: 2018-10-01
- Venue: Nature Communications
- DOI: https://doi.org/10.1038/s41467-018-06621-3
- PMID: 30291246
- Citations: 265
- Source URL: https://doi.org/10.1038/s41467-018-06621-3
- PDF: https://www.nature.com/articles/s41467-018-06621-3.pdf
- Provenance: openalex

## Abstract

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.

_Abstract reproduced under CC-BY (publisher license, via OpenAlex)._

Topics: [Gene & Cell Therapy](https://space-kitty.com/topics/gene-cell-therapy)

---
Space Kitty Archive · https://space-kitty.com · API: https://space-kitty.com/api/v1 · MCP: https://space-kitty.com/mcp · Premium: $0.20/request via x402 (Base Sepolia (testnet)). Metadata: arXiv (CC0), OpenAlex (CC0), Europe PMC (CC BY/CC0 works), ClinicalTrials.gov.