title: Induction of robust immune responses against human immunodeficiency virus is supported by the inherent tropism of adeno-associated virus type 5 for dendritic cells.
abstract: The ability of adeno-associated virus serotype 1 to 8 (AAV1 to AAV8) vectors expressing the human immunodeficiency virus type 1 (HIV-1) Env gp160 (AAV-HIV) to induce an immune response was evaluated in BALB/c mice. The AAV5 vector showed a higher tropism for both mouse and human dendritic cells (DCs) than did the AAV2 vector, whereas other AAV serotype vectors transduced DCs only poorly. AAV1, AAV5, AAV7, and AAV8 were more highly expressed in muscle cells than AAV2. An immunogenicity study of AAV serotypes indicates that AAV1, AAV5, AAV7, and AAV8 vectors expressing the Env gp160 gene induced higher HIV-specific humoral and cell-mediated immune responses than the AAV2 vector did, with the AAV5 vector producing the best responses. Furthermore, mice injected with DCs that had been transduced ex vivo with an AAV5 vector expressing the gp160 gene elicited higher HIV-specific cell-mediated immune responses than did DCs transduced with AAV1 and AAV2 vectors. We also found that AAV vectors produced by HEK293 cells and insect cells elicit similar levels of antigen-specific immune responses. These results demonstrate that the immunogenicity of AAV vectors depends on their tropism for both antigen-presenting cells (such as DCs) and non-antigen-presenting cells (such as muscular cells) and that AAV5 is a better vector than other AAV serotypes. These results may aid in the development of AAV-based vaccine and gene therapy.
authors.affiliation: Department of Molecular Biodefense Research, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan.
authors.forename: Ke-Qin
authors.initials: KQ
authors.lastname: Xin
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Mizukami
authors.forename: Masashi
authors.initials: M
authors.lastname: Urabe
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Toda
authors.forename: Kaori
authors.initials: K
authors.lastname: Shinoda
authors.forename: Atsushi
authors.initials: A
authors.lastname: Yoshida
authors.forename: Kenji
authors.initials: K
authors.lastname: Oomura
authors.forename: Yoshitsugu
authors.initials: Y
authors.lastname: Kojima
authors.forename: Motohide
authors.initials: M
authors.lastname: Ichino
authors.forename: Dennis
authors.initials: D
authors.lastname: Klinman
authors.forename: Keiya
authors.initials: K
authors.lastname: Ozawa
authors.forename: Kenji
authors.initials: K
authors.lastname: Okuda
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D003713:Dendritic Cells / Q000276:immunology* / Q000821:virology; D000229:Dependovirus / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005822:Genetic Vectors / Q000276:immunology*; D006678:HIV / Q000276:immunology*; D019302:HIV Envelope Protein gp160 / Q000276:immunology; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D014161:Transduction, Genetic / Q000379:methods*; D001616:beta-Galactosidase / Q000378:metabolism
chemical_list: D019302:HIV Envelope Protein gp160; D001616:beta-Galactosidase