A Lipopolysaccharide from Pantoea Agglomerans Is a Promising Adjuvant for Sublingual Vaccines to Induce Systemic and Mucosal Immune Responses in Mice via TLR4 Pathway

Masahiro Fukasaka; Daisuke Asari; Eiji Kiyotoh; Arimichi Okazaki; Yasuyuki Gomi; Takeshi Tanimoto; Osamu Takeuchi; Shizuo Akira; Mitsuhiko Hori

doi:10.1371/journal.pone.0126849

A Lipopolysaccharide from Pantoea Agglomerans Is a Promising Adjuvant for Sublingual Vaccines to Induce Systemic and Mucosal Immune Responses in Mice via TLR4 Pathway

PLoS One. 2015 May 15;10(5):e0126849. doi: 10.1371/journal.pone.0126849. eCollection 2015.

Authors

Masahiro Fukasaka¹, Daisuke Asari¹, Eiji Kiyotoh¹, Arimichi Okazaki¹, Yasuyuki Gomi², Takeshi Tanimoto², Osamu Takeuchi³, Shizuo Akira⁴, Mitsuhiko Hori¹

Affiliations

¹ Life Science Research Center, Corporate Research & Development Division, Nitto Denko Corporation, Ibaraki, Osaka, Japan.
² Research and Production Technology Department, The Research Foundation for Microbial Diseases of Osaka University, Kanonji, Kagawa, Japan.
³ Laboratory of Infection and Prevention, Institute for Virus Research, Kyoto University, Shogoin Kawara-cho, Sakyo-ku, Kyoto, Japan.
⁴ Laboratory of Host Defense, WPI Immunology Frontier Research Center (IFReC), Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adjuvants, Immunologic / administration & dosage
Adjuvants, Immunologic / pharmacology*
Administration, Sublingual
Animals
Enzyme-Linked Immunosorbent Assay
Female
Immunity, Humoral / drug effects*
Immunity, Humoral / immunology
Immunity, Mucosal / drug effects*
Immunity, Mucosal / immunology
Immunoglobulin A / immunology
Immunoglobulin G / immunology
Influenza A Virus, H1N1 Subtype / immunology
Influenza A Virus, H3N2 Subtype / immunology
Influenza Vaccines / administration & dosage
Influenza Vaccines / immunology*
Lipopolysaccharides / administration & dosage
Lipopolysaccharides / immunology
Lipopolysaccharides / pharmacology*
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Pantoea / immunology*
Toll-Like Receptor 4 / physiology*

Substances

Adjuvants, Immunologic
Immunoglobulin A
Immunoglobulin G
Influenza Vaccines
Lipopolysaccharides
Tlr4 protein, mouse
Toll-Like Receptor 4

Grants and funding

Nitto Denko Corporation provided support in the form of salaries for authors MF, DA, EK, AO, and MH, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the author contributions section.