Persistence of Integrase-Deficient Lentiviral Vectors Correlates with the Induction of STING-Independent CD8+ T Cell Responses

Céline Cousin, Marine Oberkampf, Tristan Felix, Pierre Rosenbaum, Robert Weil, Sylvie Fabrega, Valeria Morante, Donatella Negri, Andrea Cara, Gilles Dadaglio, Claude Leclerc

Research output: Contribution to journalArticlepeer-review


Lentiviruses are among the most promising viral vectors for in vivo gene delivery. To overcome the risk of insertional mutagenesis, integrase-deficient lentiviral vectors (IDLVs) have been developed. We show here that strong and persistent specific cytotoxic T cell (CTL) responses are induced by IDLVs, which persist several months after a single injection. These responses were associated with the induction of mild and transient maturation of dendritic cells (DCs) and with the production of low levels of inflammatory cytokines and chemokines. They were independent of the IFN-I, TLR/MyD88, interferon regulatory factor (IRF), retinoic acid induced gene I (RIG-I), and stimulator of interferon genes (STING) pathways but require NF-κB signaling in CD11c+ DCs. Despite the lack of integration of IDLVs, the transgene persists for 3 months in the spleen and liver of IDLV-injected mice. These results demonstrate that the capacity of IDLVs to trigger persistent adaptive responses is mediated by a weak and transient innate response, along with the persistence of the vector in tissues.

Original languageEnglish
Pages (from-to)1242-1257.e7
JournalCell Reports
Issue number5
Publication statusPublished - Jan 29 2019


  • antigen persistence
  • cytotoxic T cell responses
  • vaccines
  • integrase-deficient lentiviral vectors
  • memory
  • pattern recognition receptors

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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