title: Oral Gavage Delivery of PR8 Antigen with β-Glucan-Conjugated GRGDS Carrier to Enhance M-Cell Targeting Ability and Induce Immunity.
abstract: Oral gavage is known as one of most convenient routes for therapeutic administration in comparison with other available routes such as intravenous, intra muscular, suppository, etc. An oral vaccine delivery system has additional potential as it may provide a convenient way to prevent infectious diseases by introducing optimum immunization in mucus. Although oral vaccine delivery has attracted tremendous interest in vaccine delivery research, various limitations have prevented its rate of progress up to the level that was initially expected. However, the major problems of oral vaccine delivery are vaccine instability and lack of absorbability, resulting from degradation of the sophisticated antigens in the acidic medium in the stomach. In order to obtain adequate microfold-cell (M-cell) targeting and uptake, the therapeutic material is required to pass through the stomach and reach the small intestine without degradation. In this project, we have introduced a conjugate of β-glucan and Glycine-Arginine-Glycine-Aspartic acid-Serine (GRGDS) that is effective for simultaneous protection of the antigen (PR8) and M-cell targeting. According to the experimental results, the cationic β-glucan-GRGDS conjugate can encapsulate a certain amount of anionic PR8 through electrostatic interaction, which forms nanoparticles with a range of diameter of 200-250 nm. Also, the PR8 incorporated nanoparticles showed high cell viability and stability in diverse environments. Finally, excellent M-cell targeting ability was verified in an in vitro M-cell model. Most importantly, the in vivo test obviously demonstrated the superiority of this system, which significantly increases antibody concentration in serum, intestine, and mucus as measured 21 days after immunization.
authors.affiliation: Department of Chemical & Biomolecular Engineering, Korea Advanced Institute of Science and Technology , Daejeon, Korea.
authors.forename: Dong-Yi
authors.initials: DY
authors.lastname: Lee
authors.affiliation: Department of Polymer Science & Engineering, Chungnam National University , Daejeon, Korea.|Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School , Boston, United States 02129.
authors.forename: Md
authors.identifier: 0000-0003-4457-3401
authors.initials: M
authors.lastname: Nurunnabi
authors.affiliation: Department of Chemical & Biological Engineering, Korea National University of Transportation , Chungju-380-702, Korea.
authors.forename: Sung Hun
authors.initials: SH
authors.lastname: Kang
authors.affiliation: Department of Green Bioengineering, Korea National University of Transportation , Chungju 380-702, Korea.
authors.forename: Md
authors.initials: M
authors.lastname: Nafiujjaman
authors.affiliation: Department of Polymer Science & Engineering, Chungnam National University , Daejeon, Korea.
authors.forename: Kang Moo
authors.identifier: 0000-0002-2406-6659
authors.initials: KM
authors.lastname: Huh
authors.affiliation: Department of Chemical & Biological Engineering, Korea National University of Transportation , Chungju-380-702, Korea.|Department of Green Bioengineering, Korea National University of Transportation , Chungju 380-702, Korea.
authors.forename: Yong-Kyu
authors.initials: YK
authors.lastname: Lee
authors.affiliation: Department of Chemical & Biomolecular Engineering, Korea Advanced Institute of Science and Technology , Daejeon, Korea.
authors.forename: Yeu-Chun
authors.identifier: 0000-0002-7747-1455
authors.initials: YC
authors.lastname: Kim
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000956:Antigens, Viral / Q000008:administration & dosage / Q000276:immunology*; D018938:Caco-2 Cells; D002470:Cell Survival / Q000187:drug effects; D004337:Drug Carriers / Q000737:chemistry*; D005260:Female; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype; D007413:Intestinal Mucosa / Q000166:cytology*; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry; D009842:Oligopeptides / Q000737:chemistry* / Q000276:immunology; D014018:Tissue Distribution; D014612:Vaccines / Q000276:immunology; D018074:Vaccines, Conjugate; D047071:beta-Glucans / Q000737:chemistry* / Q000276:immunology
chemical_list: D000956:Antigens, Viral; D004337:Drug Carriers; D009842:Oligopeptides; D014612:Vaccines; D018074:Vaccines, Conjugate; D047071:beta-Glucans; C049554:glycyl-arginyl-glycyl-aspartyl-serine