title: Targeting the vaginal mucosa with human papillomavirus pseudovirion vaccines delivering simian immunodeficiency virus DNA.
abstract: The majority of HIV infections occur via mucosal transmission. Vaccines that induce memory T and B cells in the female genital tract may prevent the establishment and systemic dissemination of HIV. We tested the immunogenicity of a vaccine that uses human papillomavirus (HPV)-based gene transfer vectors, also called pseudovirions (PsVs), to deliver SIV genes to the vaginal epithelium. Our findings demonstrate that this vaccine platform induces gene expression in the genital tract in both cynomolgus and rhesus macaques. Intravaginal vaccination with HPV16, HPV45, and HPV58 PsVs delivering SIV Gag DNA induced Gag-specific Abs in serum and the vaginal tract, and T cell responses in blood, vaginal mucosa, and draining lymph nodes that rapidly expanded following intravaginal exposure to SIV(mac251.) HPV PsV-based vehicles are immunogenic, which warrant further testing as vaccine candidates for HIV and may provide a useful model to evaluate the benefits and risks of inducing high levels of SIV-specific immune responses at mucosal sites prior to SIV infection.
authors.affiliation: Animal Models and Retroviral Vaccines Section, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Shari N
authors.initials: SN
authors.lastname: Gordon
authors.forename: Rhonda C
authors.initials: RC
authors.lastname: Kines
authors.forename: Galyna
authors.initials: G
authors.lastname: Kutsyna
authors.forename: Zhong-Min
authors.initials: ZM
authors.lastname: Ma
authors.forename: Anna
authors.initials: A
authors.lastname: Hryniewicz
authors.forename: Jeffery N
authors.initials: JN
authors.lastname: Roberts
authors.forename: Claudio
authors.initials: C
authors.lastname: Fenizia
authors.forename: Rachmat
authors.initials: R
authors.lastname: Hidajat
authors.forename: Egidio
authors.initials: E
authors.lastname: Brocca-Cofano
authors.forename: Nicolas
authors.initials: N
authors.lastname: Cuburu
authors.forename: Christopher B
authors.initials: CB
authors.lastname: Buck
authors.forename: Marcelino L
authors.initials: ML
authors.lastname: Bernardo
authors.forename: Marjorie
authors.initials: M
authors.lastname: Robert-Guroff
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Miller
authors.forename: Barney S
authors.initials: BS
authors.lastname: Graham
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Lowy
authors.forename: John T
authors.initials: JT
authors.lastname: Schiller
authors.forename: Genoveffa
authors.initials: G
authors.lastname: Franchini
mesh_terms: D052685:Alphapapillomavirus / Q000235:genetics / Q000276:immunology; D000818:Animals; D004279:DNA, Viral / Q000008:administration & dosage* / Q000276:immunology; D005260:Female; D015683:Gene Products, gag / Q000008:administration & dosage / Q000235:genetics* / Q000276:immunology; D018014:Gene Transfer Techniques; D057809:HEK293 Cells; D006801:Humans; D018928:Immunity, Mucosal / Q000235:genetics; D008164:Luminescent Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D008252:Macaca fascicularis; D008253:Macaca mulatta; D030361:Papillomavirus Infections / Q000235:genetics / Q000276:immunology / Q000821:virology; D053918:Papillomavirus Vaccines / Q000008:administration & dosage* / Q000235:genetics* / Q000276:immunology; D016097:Simian Acquired Immunodeficiency Syndrome / Q000235:genetics / Q000276:immunology / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000235:genetics* / Q000276:immunology; D014621:Vagina / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D014771:Virion / Q000235:genetics* / Q000276:immunology; D000097573:Red Fluorescent Protein
chemical_list: D004279:DNA, Viral; D015683:Gene Products, gag; D008164:Luminescent Proteins; D053918:Papillomavirus Vaccines; D000097573:Red Fluorescent Protein