title: Combinatorial Approach of Antigen Delivery Using M Cell-Homing Peptide and Mucoadhesive Vehicle to Enhance the Efficacy of Oral Vaccine.
abstract: Orally ingested pathogens or antigens are taken up by microfold cells (M cells) in Peyer's patches of intestine to initiate protective immunity against infections. However, the uptake of orally delivered protein antigens through M cells is very low due to lack of specificity of proteins toward M cells and degradation of proteins in the harsh environment of gastrointestinal (GI) tract. To overcome these limitations, here we developed a pH-sensitive and mucoadhesive vehicle of thiolated eudragit (TE) microparticles to transport an M cell-targeting peptide-fused model protein antigen. Particularly, TE prolonged the particles transit time through the GI tract and predominantly released the proteins in ileum where M cells are abundant. Thus, oral delivery of TE microparticulate antigens exhibited high transcytosis of antigens through M cells resulting in strong protective sIgA as well as systemic IgG antibody responses. Importantly, the delivery system not only induced CD4(+) T cell immune responses but also generated strong CD8(+) T cell responses with enhanced production of IFN-γ in spleen. Given that M cells are considered a promising target for oral vaccination, this study could provide a new combinatorial method for the development of M-cell-targeted mucosal vaccines.
authors.affiliation: Department of Agricultural Biotechnology, Seoul National University , Seoul 151-921, Korea.|Research Institute for Agriculture and Life Sciences, Seoul National University , Seoul 151-921, Korea.
authors.forename: Bijay
authors.initials: B
authors.lastname: Singh
authors.affiliation: Department of Agricultural Biotechnology, Seoul National University , Seoul 151-921, Korea.|Research Institute for Agriculture and Life Sciences, Seoul National University , Seoul 151-921, Korea.
authors.forename: Sushila
authors.initials: S
authors.lastname: Maharjan
authors.affiliation: Department of Agricultural Biotechnology, Seoul National University , Seoul 151-921, Korea.|Research Institute for Agriculture and Life Sciences, Seoul National University , Seoul 151-921, Korea.
authors.forename: Tao
authors.initials: T
authors.lastname: Jiang
authors.affiliation: Department of Agricultural Biotechnology, Seoul National University , Seoul 151-921, Korea.|Research Institute of Eco-friendly Animal Science, Institute of Green-Bio Science and Technology, Seoul National University , Kangwon-Do 232-916, Republic of Korea.
authors.forename: Sang-Kee
authors.initials: SK
authors.lastname: Kang
authors.affiliation: Department of Agricultural Biotechnology, Seoul National University , Seoul 151-921, Korea.|Research Institute for Agriculture and Life Sciences, Seoul National University , Seoul 151-921, Korea.
authors.forename: Yun-Jaie
authors.initials: YJ
authors.lastname: Choi
authors.affiliation: Department of Agricultural Biotechnology, Seoul National University , Seoul 151-921, Korea.|Research Institute for Agriculture and Life Sciences, Seoul National University , Seoul 151-921, Korea.
authors.forename: Chong-Su
authors.initials: CS
authors.lastname: Cho
mesh_terms: D000180:Acrylic Resins; D000284:Administration, Oral; D000818:Animals; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002448:Cell Adhesion / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism; D016503:Drug Delivery Systems; D005260:Female; D005434:Flow Cytometry; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000166:cytology; D008074:Lipoproteins / Q000276:immunology*; D008422:Materials Testing; D051379:Mice; D008807:Mice, Inbred BALB C; D008863:Microspheres; D010446:Peptide Fragments / Q000008:administration & dosage* / Q000276:immunology; D011108:Polymers / Q000737:chemistry; D022223:Vaccines, Subunit / Q000008:administration & dosage* / Q000276:immunology
chemical_list: D000180:Acrylic Resins; D001425:Bacterial Outer Membrane Proteins; C415945:BmpB protein, Brachyspira hyodysenteriae; D016207:Cytokines; C446821:Eudragit L100-55; D008074:Lipoproteins; D010446:Peptide Fragments; D011108:Polymers; D022223:Vaccines, Subunit
keywords: M cells; microparticles; mucoadhesive vehicle; mucosal vaccine; oral delivery