title: Mucosal vaccination with a live recombinant rhinovirus followed by intradermal DNA administration elicits potent and protective HIV-specific immune responses.
abstract: Mucosal immunity is deemed crucial to control sexual transmission of human immunodeficiency virus (HIV). Herein we report the efficacy of a mucosal HIV vaccine strategy comprising intranasal (IN) vaccination with a cocktail of live recombinant human rhinoviruses (HRVs) encoding overlapping fragments of HIV Gag and full length Tat (rHRV-Gag/Tat) followed by intradermal (ID) vaccination with DNA vaccines encoding HIV Gag and Tat (pVAX-Gag-Tat). This heterologous prime-boost strategy will be referred to hereafter as rHRV-DNA. As a control, IN vaccination with wild type (wt)-HRV-A1 followed by a single ID dose of pVAX (wt-HRV-A1/pVAX vaccination) was included. rHRV-DNA vaccination elicited superior multi-functional CD8+T cell responses in lymphocytes harvested from mesenteric lymph nodes and spleens, and higher titres of Tat-specific antibodies in blood and vaginal lavages, and reduced the viral load more effectively after challenge with EcoHIV, a murine HIV challenge model, in peritoneal macrophages, splenocytes and blood compared compared with wt-HRV-A1/pVAX vaccination or administration of 3 ID doses of pVAX-Gag-Tat (3X pVAX-Gag-Tat vaccination). These data provide the first evidence that a rHRV-DNA vaccination regimen can induce HIV-specific immune responses in the gut, vaginal mucosa and systemically, and supports further testing of this regimen in the development of an effective mucosally-targeted HIV-1 vaccine.
authors.affiliation: Virology Laboratory, Basil Hetzel Institute, Discipline of Surgery, University of Adelaide, Adelaide, South Australia, Australia.
authors.forename: Khamis
authors.initials: K
authors.lastname: Tomusange
authors.affiliation: Virology Laboratory, Basil Hetzel Institute, Discipline of Surgery, University of Adelaide, Adelaide, South Australia, Australia.
authors.forename: Danushka
authors.initials: D
authors.lastname: Wijesundara
authors.affiliation: Virology Laboratory, Basil Hetzel Institute, Discipline of Surgery, University of Adelaide, Adelaide, South Australia, Australia.
authors.forename: Jason
authors.initials: J
authors.lastname: Gummow
authors.affiliation: South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia.
authors.forename: Steve
authors.initials: S
authors.lastname: Wesselingh
authors.affiliation: QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
authors.forename: Andreas
authors.initials: A
authors.lastname: Suhrbier
authors.affiliation: Virology Laboratory, Basil Hetzel Institute, Discipline of Surgery, University of Adelaide, Adelaide, South Australia, Australia.
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Gowans
authors.affiliation: Virology Laboratory, Basil Hetzel Institute, Discipline of Surgery, University of Adelaide, Adelaide, South Australia, Australia.
authors.forename: Branka
authors.initials: B
authors.lastname: Grubor-Bauk
mesh_terms: D016915:AIDS Vaccines / Q000235:genetics / Q000276:immunology / Q000494:pharmacology; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D015658:HIV Infections / Q000235:genetics / Q000276:immunology / Q000517:prevention & control*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular; D051379:Mice; D008807:Mice, Inbred BALB C; D012229:Rhinovirus; D019444:Vaccines, DNA / Q000235:genetics / Q000276:immunology / Q000494:pharmacology; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000276:immunology / Q000494:pharmacology; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000276:immunology / Q000494:pharmacology
chemical_list: D016915:AIDS Vaccines; D019444:Vaccines, DNA; D054301:gag Gene Products, Human Immunodeficiency Virus; D054322:tat Gene Products, Human Immunodeficiency Virus