title: A Prime-Boost Strategy Combining Intravaginal and Intramuscular Administration of Homologous Adenovirus to Enhance Immune Response Against HIV-1 in Mice.
abstract: Immune responses to HIV in the vaginal tract effectively trigger both systemic and mucosal protection, providing a double layer of defense. However, recombinant adenoviral (rAd) vectors delivered intravaginally do not effectively penetrate the mucus layer and vaginal epithelium, and instead are rapidly cleared. To overcome these barriers, we previously synthesized a novel cationic polyethylene glycol derivative that can self-assemble into nanocomplexes with rAd. These nanocomplexes can help rAd bypass the mucus layer and enhance mucosal immune response to the encoded antigen. However, the resulting cellular and humoral responses were still lower than those elicited by single intramuscular injection of rAd. Therefore, in the present study we investigated a new vaccination strategy involving intravaginal priming with our nanocomplexes, followed by an intramuscular boost with rAd-gag. Mice immunized in this way showed more potent humoral and cellular responses, as well as higher IgA levels, than animals primed and boosted intravaginally with nanocomplexes. These results show the promise of a prime-boost strategy for developing vaccine candidates against HIV.
authors.affiliation: Key Laboratory of Drug Targeting and Novel Drug Delivery Systems, West China School of Pharmacy, Sichuan University , Ministry of Education, Chengdu, Sichuan, 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, Chengdu, Sichuan, 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, Chengdu, Sichuan, People's Republic of China .
authors.forename: Qin
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Key Laboratory of Drug Targeting and Novel Drug Delivery Systems, West China School of Pharmacy, Sichuan University , Ministry of Education, Chengdu, Sichuan, 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, Chengdu, Sichuan, 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, Chengdu, Sichuan, People's Republic of China .
authors.forename: Xun
authors.initials: X
authors.lastname: Sun
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D000256:Adenoviridae / Q000235:genetics; D000282:Administration, Intravaginal; D000818:Animals; D003602:Cytotoxicity, Immunologic; D004195:Disease Models, Animal; D005260:Female; D005822:Genetic Vectors / Q000008:administration & dosage / Q000235:genetics; D015483:HIV Antibodies / Q000276:immunology; D015658:HIV Infections / Q000276:immunology* / Q000517:prevention & control; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D007114:Immunization; D007117:Immunization, Secondary; D007156:Immunologic Memory; D007273:Injections, Intramuscular; D007371:Interferon-gamma; D051379:Mice; D053761:Nanocomposites; D037182:T-Cell Antigen Receptor Specificity / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D014162:Transfection / Q000379:methods
chemical_list: D016915:AIDS Vaccines; D015483:HIV Antibodies; D007371:Interferon-gamma