title: Engineering intravaginal vaccines to overcome mucosal and epithelial barriers.
abstract: The mucosal surface of the vagina is a primary human immunodeficiency virus (HIV) entry portal, making it an attractive site for HIV vaccination. However, HIV vaccines based on recombinant adenovirus (rAd) do not efficiently cross the mucus layers or underlying epithelium of the vagina. Here we designed nanocomplexes of rAd particles coated with (1) the polyethylene glycol derivative APS to provide a hydrophilic surface that would prevent entrapment in the hydrophobic mucus, and (2) the cell-penetrating peptide TAT to improve transduction efficiency. The optimized rAd-TAT-APS nanocomplexes could achieve the balance of effective mucus-penetrating and cellular transduction. Intravaginal delivery of rAd-TAT-APS encoding HIVgag p24 into mice strongly enhanced HIVgag-specific systemic and mucosal immune responses. This rAd-TAT-APS system may allow effective vaginal delivery of vaccines against HIV and other infectious agents.
authors.affiliation: Key Laboratory of Drug Targeting and Novel Drug Delivery Systems, West China School of Pharmacy, Sichuan University, Ministry of Education, People's Republic of China.
authors.forename: Zhonghua
authors.initials: Z
authors.lastname: Ji
authors.affiliation: Key Laboratory of Drug Targeting and Novel Drug Delivery Systems, West China School of Pharmacy, Sichuan University, Ministry of Education, People's Republic of China.
authors.forename: Zhaolu
authors.initials: Z
authors.lastname: Xie
authors.affiliation: Key Laboratory of Drug Targeting and Novel Drug Delivery Systems, West China School of Pharmacy, Sichuan University, Ministry of Education, People's Republic of China.
authors.forename: Zhirong
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Drug Targeting and Novel Drug Delivery Systems, West China School of Pharmacy, Sichuan University, Ministry of Education, People's Republic of China.
authors.forename: Tao
authors.initials: T
authors.lastname: Gong
authors.affiliation: Key Laboratory of Drug Targeting and Novel Drug Delivery Systems, West China School of Pharmacy, Sichuan University, Ministry of Education, People's Republic of China. Electronic address: sunxun@scu.edu.cn.
authors.forename: Xun
authors.initials: X
authors.lastname: Sun
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D000256:Adenoviridae / Q000378:metabolism; D000282:Administration, Intravaginal; D000818:Animals; D000917:Antibody Formation / Q000187:drug effects; D055592:Biophysical Phenomena; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D004058:Diffusion; D004705:Endocytosis; D058501:Enzyme-Linked Immunospot Assay; D004847:Epithelial Cells / Q000378:metabolism; D004848:Epithelium / Q000187:drug effects / Q000276:immunology*; D005260:Female; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D007114:Immunization; D008807:Mice, Inbred BALB C; D009092:Mucous Membrane / Q000187:drug effects / Q000276:immunology*; D009093:Mucus / Q000378:metabolism; D053758:Nanoparticles / Q000737:chemistry / Q000633:toxicity / Q000648:ultrastructure; D011092:Polyethylene Glycols / Q000138:chemical synthesis / Q000737:chemistry; D011995:Recombination, Genetic / Q000235:genetics; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology; D014161:Transduction, Genetic; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000378:metabolism
chemical_list: D016915:AIDS Vaccines; D054301:gag Gene Products, Human Immunodeficiency Virus; D049452:Green Fluorescent Proteins; D011092:Polyethylene Glycols
keywords: Adenovirus; Anionic PEG derivative; Intravaginal immunization; Mucus; TAT