title: Intranasal Vaccination against HIV-1 with Adenoviral Vector-Based Nanocomplex Using Synthetic TLR-4 Agonist Peptide as Adjuvant.
abstract: Recombinant type 5 adenovirus (rAd5) vaccines hold the promise to prevent HIV-1 infections. Intranasal vaccination not only stimulates systemic immunity but also elicits mucosal immunity that provides first defense for mucosally transmitted diseases like HIV-1. Adjuvants such as TLR agonists are usually codelivered with antigens to enhance the immunogenicity of vaccines. Here, we present a rAd5 vaccine delivery system using DEG-PEI as the carrier. Adenovirus encoding HIV gag was used as antigen, and was complexed with DEG-PEI polymer via electrostatic interaction. A novel synthetic TLR-4 agonist, RS09, was either chemically linked with DEG-PEI (DP-RS09) or physically mixed with it(DP/RS09) to enhance the immunogenticity of rAd5 vaccine. After intranasal immunization, the systemic antigen-specific immune responses and cytotoxicity T lymphocytes responses induced by DP-RS09-rAd5 and DP/RS09-rAd5 were analyzed. The mucosal secretory IgA level was detected in both nasal and vaginal washes to determine the mucosal immunity. Furthermore, cytokine productions on RAW264.7 cells were tested after preincubation with TLR-4 pathway inhibitors. The results indicated that DEG-PEI could facilitate the intranasal delivery of rAd5 vaccine. Both chemically linked (DP-RS09) and physically mixed RS09 (DP/RS09) could further enhance the mucosal immunity of rAd5 vaccine via TLR-4 pathway. This RS09 adjuvanted DEG-PEI polymer represents a potential intranasal vaccine delivery system and may have a wider application for other viral vectors.
authors.affiliation: Key Laboratory of Drug Targeting, Ministry of Education, West China School of Pharmacy, Sichuan University , Chengdu, 610041, People's Republic of China.
authors.forename: Man
authors.initials: M
authors.lastname: Li
authors.affiliation: Key Laboratory of Drug Targeting, Ministry of Education, West China School of Pharmacy, Sichuan University , Chengdu, 610041, People's Republic of China.
authors.forename: Yuhong
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Key Laboratory of Drug Targeting, Ministry of Education, West China School of Pharmacy, Sichuan University , Chengdu, 610041, People's Republic of China.
authors.forename: Tao
authors.initials: T
authors.lastname: Gong
authors.affiliation: Key Laboratory of Drug Targeting, Ministry of Education, West China School of Pharmacy, Sichuan University , Chengdu, 610041, People's Republic of China.
authors.forename: Zhirong
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Drug Targeting, Ministry of Education, West China School of Pharmacy, Sichuan University , Chengdu, 610041, People's Republic of China.
authors.forename: Xun
authors.initials: X
authors.lastname: Sun
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage*; D000256:Adenoviridae / Q000235:genetics*; D000276:Adjuvants, Immunologic; D000281:Administration, Intranasal; D000818:Animals; D049109:Cell Proliferation; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology; D004285:Dogs; D004337:Drug Carriers; D005260:Female; D005822:Genetic Vectors / Q000008:administration & dosage*; D015658:HIV Infections / Q000276:immunology / Q000517:prevention & control*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D018928:Immunity, Mucosal; D061985:Madin Darby Canine Kidney Cells; D051379:Mice; D008807:Mice, Inbred BALB C; D049329:Nanostructures / Q000737:chemistry*; D009297:Nasal Mucosa / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000819:agonists* / Q000276:immunology; D014611:Vaccination
chemical_list: D016915:AIDS Vaccines; D000276:Adjuvants, Immunologic; D004337:Drug Carriers; D010446:Peptide Fragments; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4
keywords: RS09; TLR4; adenovirus vaccine; intranasal delivery