title: Responses of primary human nasal epithelial cells to EDIII-DENV stimulation: the first step to intranasal dengue vaccination.
abstract: About half of the world's population are living in the endemic area of dengue viruses implying that a rapid-mass vaccination may be required. In addition, a major target of dengue vaccine are children, thus, a needle-free administration is more attractive. These problems may be overcome by the alternative route of vaccination such as topical, oral and intranasal vaccination. Here, we investigated the possibility to deliver a dengue immunogen intranasally, a painless route of vaccination. The tested immunogen was the domain III of dengue serotype-3 E protein (EDIII-D3) loaded into trimethyl chitosan nanoparticles (EDIII-D3 TMC NPs). The primary human nasal epithelial cells, HNEpCs, were used as an in vitro model for nasal responses.
  
  
  
  At tested concentrations, EDIII-D3 TMC NPs not only exerted no detectable toxicity toward HNEpC cultures but also efficiently delivered EDIII-D3 immunogens into HNEpCs. Moreover, HNEpCs quickly and strongly produced proinflammatory cytokines (IL-1β, IL-6, TNF-α), type-I IFN, the growth factors (GM-CSF, IL-7), the chemokines (MCP-1, MIP-1β, IL-8), Th1-related cytokines (IL-2, IL-12p70, IL-17, IFN-γ) and Th2-related cytokine (IL-4) in response to EDIII-D3 TMC NPs treatment.
  
  
  
  A potential mucosal delivery system for dengue immunogens was revealed and found to stimulate a strong local innate antiviral response which possibly leading to a systemic adaptive immunity.
authors.affiliation: Department of Microbiology, Faculty of Science, Mahidol University, Bangkok, 10400, Thailand.
authors.forename: Nattika
authors.initials: N
authors.lastname: Nantachit
authors.affiliation: Department of Chemistry, Faculty of Science, Mahidol University, Bangkok, 10400, Thailand.
authors.forename: Panya
authors.initials: P
authors.lastname: Sunintaboon
authors.affiliation: Department of Microbiology, Faculty of Science, Mahidol University, Bangkok, 10400, Thailand. sukathida.ubo@mahidol.ac.th.
authors.forename: Sukathida
authors.initials: S
authors.lastname: Ubol
mesh_terms: D000281:Administration, Intranasal; D003715:Dengue / Q000276:immunology / Q000821:virology*; D053059:Dengue Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D003716:Dengue Virus / Q000235:genetics / Q000276:immunology*; D004847:Epithelial Cells / Q000276:immunology* / Q000821:virology; D006801:Humans; D007376:Interleukin-2 / Q000276:immunology; D016209:Interleukin-8 / Q000276:immunology; D009666:Nose / Q000166:cytology / Q000276:immunology / Q000821:virology; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D014611:Vaccination; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology*; D014765:Viral Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*
chemical_list: D053059:Dengue Vaccines; C084188:E protein, Dengue virus type 3; D007376:Interleukin-2; D016209:Interleukin-8; D014759:Viral Envelope Proteins; D014765:Viral Vaccines
keywords: Dengue vaccine; Domain III of dengue virus; Nasal stimulation; Trimethyl chitosan nanoparticles