title: GP120-specific exosome-targeted T cell-based vaccine capable of stimulating DC- and CD4(+) T-independent CTL responses.
abstract: The limitations of highly active anti-retroviral therapy (HAART) have necessitated the development of alternative therapeutics. In this study, we generated ovalbumin (OVA)-pulsed and pcDNAgp120-transfected dendritic cell (DC)-released exosomes (EXOova and EXOgp120) and ConA-stimulated C57BL/6 CD8(+) T cells. OVA- and Gp120-Texo vaccines were generated from CD8(+) T cells with uptake of EXOova and EXOgp120, respectively. We demonstrate that OVA-Texo stimulates in vitro and in vivo OVA-specific CD4(+) and CD8(+) cytotoxic T lymphocyte (CTL) responses leading to long-term immunity against OVA-expressing BL6-10(OVA) melanoma. Interestingly, CD8(+) T cell responses are DC and CD4(+) T cell independent. Importantly, Gp120-Texo also stimulates Gp120-specific CTL responses and long-term immunity against Gp120-expressing B16 melanoma. Therefore, this novel HIV-1-specific EXO-targeted Gp120-Texo vaccine may be useful in induction of efficient CTL responses in AIDS patients with DC dysfunction and CD4(+) T cell deficiency.
authors.affiliation: Cancer Research Unit, Research Division, Saskatchewan Cancer Agency, Saskatoon, Saskatchewan, Canada.
authors.forename: Roopa Hebbandi
authors.initials: RH
authors.lastname: Nanjundappa
authors.forename: Rong
authors.initials: R
authors.lastname: Wang
authors.forename: Yufeng
authors.initials: Y
authors.lastname: Xie
authors.forename: Channakeshava Sokke
authors.initials: CS
authors.lastname: Umeshappa
authors.forename: Rajni
authors.initials: R
authors.lastname: Chibbar
authors.forename: Yangdou
authors.initials: Y
authors.lastname: Wei
authors.forename: Qiang
authors.initials: Q
authors.lastname: Liu
authors.forename: Jim
authors.initials: J
authors.lastname: Xiang
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology*; D000163:Acquired Immunodeficiency Syndrome / Q000517:prevention & control; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D019496:Cancer Vaccines / Q000276:immunology*; D002460:Cell Line; D003713:Dendritic Cells / Q000276:immunology*; D055354:Exosomes / Q000276:immunology; D005260:Female; D015699:HIV Envelope Protein gp120 / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology; D007111:Immunity, Cellular; D007156:Immunologic Memory / Q000276:immunology; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology; D008546:Melanoma, Experimental / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000276:immunology
chemical_list: D016915:AIDS Vaccines; D019496:Cancer Vaccines; D015699:HIV Envelope Protein gp120; D018799:Intercellular Adhesion Molecule-1; D010047:Ovalbumin