Locoregional intravenous delivery of AAV vector in macaque results in persistent transgene expression despite a dedicated humoral and cellular immune response

Gwaldys Gernoux (1) , Marie Devaux (1) , Laurence Dubreil (2) , Nicolas Jaulin (1) , Mickaël Guilbaud (1) , Jack-Yves Deschamps (2) , Thibaut Larcher (2) , Lydie Guigand (2) , Maeva Dutilleul (2) , Caroline Le Guiner (1) , Yan Cherel (2) , Philippe Mouillier (3, 1) , Oumeya Adjali (1)

1 Inserm UMR 1089 - Laboratoire de Thérapie Génique Translationnelle des Maladies Génétiques
2 PAnTher - Physiopathologie Animale et bioThérapie du muscle et du système nerveux
3 UF - University of Florida [Gainesville]

After LR delivery of an AAV8 vector expressing GFP in non-human primates, we showed detection of transgene expression until at least 8 months post-injection in contrast to IM where GFP was lost at 3 months post-injection. Interestingly, GFP persistence after LR was observed despite the detection of anti-GFP IgG antibodies, even at higher titers than IM route, and the presence of T cells responding to GFP peptides in the spleen. Surprisingly, GFP-restimulated T cells secreted IFNγ but not IL2 after LR as compared to IM route where both cytokines were detected.

Domaines: Immunité adaptative; Immunité innée; Biotechnologies

Gwaldys Gernoux, Marie Devaux, Laurence Dubreil, Nicolas Jaulin, Mickaël Guilbaud, et al.. Locoregional intravenous delivery of AAV vector in macaque results in persistent transgene expression despite a dedicated humoral and cellular immune response. 16th annual meeting, May 2013, Salt Lake City, United States. 2013. ⟨hal-01190314⟩