title: Adenoviral vectors coated with cationic PEG derivatives for intravaginal vaccination against HIV-1.
abstract: Mucus layer coating the vaginal epithelium represents a barrier for intravaginally delivered recombined adenoviral (rAd) vectors, but it could be overcome by proper polyethylene glycol (PEG) modification. Here we synthesized two cationic PEG derivatives, amino-(EO)n/(AGE)m-Cyss (APCs). The polymers contained neutral linear PEG (2-5 kDa) to provide a hydrophilic surface and amine pendants to provide positive charge for coating negatively charged rAd by physical adsorption. Given proper molecular composition, the polymer (5k-APC) could coat rAd without causing aggregation, facilitating its mucus penetrating ability and enhancing gene expression both in vitro and in vivo. With HIVgag as the model antigen, the polymer-rAd complexes were administered intravaginally to elicit both systemic and mucosal immune responses. 5k-APC-rAd immunization elicited robust HIVgag-specific cellular responses and also induced higher antigen-specific serum IgG. More importantly, mice immunized with 5k-APC-rAd showed higher level of IgA in vaginal lavage fluid. These findings suggest that 5k-APC-rAd is a promising system for intravaginal immunization against infectious diseases such as HIV within the vaginal tract.
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu, Sichuan, PR China.
authors.forename: Zhaolu
authors.initials: Z
authors.lastname: Xie
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu, Sichuan, PR China.
authors.forename: Zhonghua
authors.initials: Z
authors.lastname: Ji
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu, Sichuan, PR China.
authors.forename: Zhirong
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu, Sichuan, PR China.
authors.forename: Tao
authors.initials: T
authors.lastname: Gong
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu, Sichuan, PR China. Electronic address: xunsun22@gmail.com.
authors.forename: Xun
authors.initials: X
authors.lastname: Sun
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000282:Administration, Intravaginal; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002412:Cations; D003713:Dendritic Cells / Q000378:metabolism; D004058:Diffusion; D004847:Epithelial Cells / Q000378:metabolism; D000939:Epitopes / Q000276:immunology; D005260:Female; D005822:Genetic Vectors / Q000378:metabolism*; D049452:Green Fluorescent Proteins / Q000378:metabolism; D015483:HIV Antibodies / Q000097:blood; D015488:HIV Antigens / Q000276:immunology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D051379:Mice; D009093:Mucus / Q000378:metabolism; D010316:Particle Size; D011092:Polyethylene Glycols / Q000138:chemical synthesis / Q000737:chemistry*; D011995:Recombination, Genetic / Q000235:genetics; D055672:Static Electricity; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014161:Transduction, Genetic; D014611:Vaccination; D014621:Vagina / Q000166:cytology
chemical_list: D002412:Cations; D000939:Epitopes; D015483:HIV Antibodies; D015488:HIV Antigens; D049452:Green Fluorescent Proteins; D011092:Polyethylene Glycols
keywords: Adenovirus; Cationic PEG derivative; Immune response; Intravaginal immunization; Mucus