title: Enhancement of nasal HIV vaccination with adenoviral vector-based nanocomplexes using mucoadhesive and DC-targeting adjuvants.
abstract: OBJECTIVE
  To investigate the vaccine effect of a replication-defective recombinant adenovirus 5 (rAd5)-based nanocomplex with chitooligosaccharides (Oligo) and mannosylated polyethyleneimine-triethyleneglycol (mPEI) as adjuvants for human immunodeficiency virus (HIV) infection.
  
  
  METHODS
  Physical characteristics were determined through detecting the size, zeta potential and morphology of Oligo-mPEI-rAd5 nanocomplex, and in vitro vaccine uptake and transduction efficiency were estimated. Nanocomplexes were then administered intranasally to Balb/c mice to evaluate in vivo rAd5 residence in nasal cavity and HIVgag-specific immune responses using cytotoxic T lymphocyte (CTL), intracellular cytokine staining (ICS) and ELISA assay.
  
  
  RESULTS
  The mucoadhesivity of Oligo prolonged nasal residence time, while the dendritic cell (DC) specificity of mPEI improved vaccine uptake. These two adjuvants jointly enhanced transduction efficiency of rAd5. Oligo-mPEI-rAd5 nanocomplex elicited potent HIVgag-specific CTL response and increased IFN-γ positive CD8(+)T and IL-4 positive CD4(+)T cells, indicating high cellular immune responses. This vaccine candidate also led to strong humoral immune responses (IgG/IgG1/IgG2a) with balanced Th1/Th2 CD4(+)T cell activity. Moreover, mice nasally immunized with Oligo-mPEI-rAd5 showed higher levels of SIgA in nasal washes than did mice immunized with rAd5.
  
  
  CONCLUSIONS
  Intranasal delivery of Oligo-mPEI-rAd5 with a prime-boost regimen is a potential immunization for HIV infection, inducing HIVgag-specific cellular, humoral and mucosal immune responses.
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, No. 17, Section 3, Southern Renmin Road, Chengdu, Sichuan, 610041, People's Republic of China.
authors.forename: Yuhong
authors.initials: Y
authors.lastname: Jiang
authors.forename: Man
authors.initials: M
authors.lastname: Li
authors.forename: Zhirong
authors.initials: Z
authors.lastname: Zhang
authors.forename: Tao
authors.initials: T
authors.lastname: Gong
authors.forename: Xun
authors.initials: X
authors.lastname: Sun
mesh_terms: D016915:AIDS Vaccines / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D000256:Adenoviridae / Q000235:genetics*; D000276:Adjuvants, Immunologic / Q000737:chemistry / Q000235:genetics*; D000281:Administration, Intranasal; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D045744:Cell Line, Tumor; D003713:Dendritic Cells / Q000276:immunology*; D004285:Dogs; D004337:Drug Carriers / Q000737:chemistry*; D005822:Genetic Vectors; D016655:HIV Core Protein p24 / Q000235:genetics* / Q000276:immunology; D015497:HIV-1 / Q000276:immunology; D006801:Humans; D061985:Madin Darby Canine Kidney Cells; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D049329:Nanostructures / Q000737:chemistry*; D009297:Nasal Mucosa / Q000276:immunology*
chemical_list: D016915:AIDS Vaccines; D000276:Adjuvants, Immunologic; D004337:Drug Carriers; D016655:HIV Core Protein p24; C514799:p24 protein, Human Immunodeficiency Virus Type 1