title: A Lipopolysaccharide from Pantoea Agglomerans Is a Promising Adjuvant for Sublingual Vaccines to Induce Systemic and Mucosal Immune Responses in Mice via TLR4 Pathway.
abstract: A lipopolysaccharide from Pantoea agglomerans (LPSpa) has been applied to various fields for human use as a Toll-like receptor 4 ligand and its safety has been confirmed. Here, we showed for the first time the application of LPSpa as an effective mucosal adjuvant for activating vaccine-induced antigen specific immune responses. Mice sublingually immunized with influenza vaccine (HA split vaccine) with LPSpa induced both HA-specific IgG (systemic) and IgA (mucosal) antibody responses, which led to a significant increase in survival rate against lethal influenza virus challenge compared with subcutaneous vaccination. After sublingual administration of ovalbumin with LPSpa, ovalbumin-specific mucosal IgA responses were induced at both mucosal surfaces close to the immunized site and at remote mucosal surfaces. Sublingual administration of LPSpa evoked local antigen-uptake by dendritic cells in cervical lymph nodes. LPSpa induced cytokine production and the maturation and proliferation of innate immune cells via Toll-like receptor 4 in dendritic cells. Collectively, these results suggest that LPSpa can be used as an effective mucosal adjuvant to stimulate and activate local innate immune cells to improve and enhance mucosal vaccine potency against various pathogens.
authors.affiliation: Life Science Research Center, Corporate Research & Development Division, Nitto Denko Corporation, Ibaraki, Osaka, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Fukasaka
authors.affiliation: Life Science Research Center, Corporate Research & Development Division, Nitto Denko Corporation, Ibaraki, Osaka, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Asari
authors.affiliation: Life Science Research Center, Corporate Research & Development Division, Nitto Denko Corporation, Ibaraki, Osaka, Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Kiyotoh
authors.affiliation: Life Science Research Center, Corporate Research & Development Division, Nitto Denko Corporation, Ibaraki, Osaka, Japan.
authors.forename: Arimichi
authors.initials: A
authors.lastname: Okazaki
authors.affiliation: Research and Production Technology Department, The Research Foundation for Microbial Diseases of Osaka University, Kanonji, Kagawa, Japan.
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Gomi
authors.affiliation: Research and Production Technology Department, The Research Foundation for Microbial Diseases of Osaka University, Kanonji, Kagawa, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Tanimoto
authors.affiliation: Laboratory of Infection and Prevention, Institute for Virus Research, Kyoto University, Shogoin Kawara-cho, Sakyo-ku, Kyoto, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Takeuchi
authors.affiliation: Laboratory of Host Defense, WPI Immunology Frontier Research Center (IFReC), Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan.
authors.forename: Shizuo
authors.initials: S
authors.lastname: Akira
authors.affiliation: Life Science Research Center, Corporate Research & Development Division, Nitto Denko Corporation, Ibaraki, Osaka, Japan.
authors.forename: Mitsuhiko
authors.initials: M
authors.lastname: Hori
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000494:pharmacology*; D000286:Administration, Sublingual; D000818:Animals; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D056724:Immunity, Humoral / Q000187:drug effects* / Q000276:immunology; D018928:Immunity, Mucosal / Q000187:drug effects* / Q000276:immunology; D007070:Immunoglobulin A / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology; D053122:Influenza A Virus, H3N2 Subtype / Q000276:immunology; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000276:immunology*; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000276:immunology / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D020636:Pantoea / Q000276:immunology*; D051197:Toll-Like Receptor 4 / Q000502:physiology*
chemical_list: D000276:Adjuvants, Immunologic; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007252:Influenza Vaccines; D008070:Lipopolysaccharides; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4