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

Abstract : 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.
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Cell Reports , Elsevier Inc, 2019, 26 (5), pp.1242-1257.e7. 〈10.1016/j.celrep.2019.01.025〉
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Soumis le : jeudi 31 janvier 2019 - 10:58:33
Dernière modification le : vendredi 15 février 2019 - 13:58:20

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Distributed under a Creative Commons Paternité 4.0 International License

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Céline Cousin, Marine Oberkampf, Tristan Felix, Pierre Rosenbaum, Robert Weil, et al.. Persistence of Integrase-Deficient Lentiviral Vectors Correlates with the Induction of STING-Independent CD8+ T Cell Responses. Cell Reports , Elsevier Inc, 2019, 26 (5), pp.1242-1257.e7. 〈10.1016/j.celrep.2019.01.025〉. 〈pasteur-02001260〉

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