title: RNA is an Adjuvanticity Mediator for the Lipid-Based Mucosal Adjuvant, Endocine.
abstract: Nasal vaccination has the potential to elicit systemic and mucosal immunity against pathogens. However, split and subunit vaccines lack potency at stimulating mucosal immunity, and an adjuvant is indispensable for eliciting potent mucosal immune response to nasal vaccines. Endocine, a lipid-based mucosal adjuvant, potentiates both systemic and mucosal immune responses. Although Endocine has shown efficacy and tolerability in animal and clinical studies, its mechanism of action remains unknown. It has been reported recently that endogenous danger signals are essential for the effects of some adjuvants such as alum or MF59. However, the contribution of danger signals to the adjuvanticity of Endocine has not been explored. Here, we show that RNA is likely to be an important mediator for the adjuvanticity of Endocine. Administration of Endocine generated nucleic acids release, and activated dendritic cells (DCs) in draining lymph nodes in vivo. These results suggest the possibility that Endocine indirectly activates DCs via damage-associated molecular patterns. Moreover, the adjuvanticity of Endocine disappeared in mice lacking TANK-binding kinase 1 (Tbk1), which is a downstream molecule of nucleic acid sensing signal pathway. Furthermore, co-administration of RNase A reduced the adjuvanticity of Endocine. These data suggest that RNA is important for the adjuvanticity of Endocine.
authors.affiliation: Laboratory of Adjuvant Innovation, National Institute of Biomedical Innovation, Health and Nutrition, Osaka 567-0085, Japan.|Laboratory of Vaccine Science, WPI Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan.|Vaccine Research Development Office, Biology Research Laboratories, Sohyaku. Innovative Research Division, Mitsubishi Tanabe Pharma Corporation, Kanagawa 227-0033, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Hayashi
authors.affiliation: Laboratory of Adjuvant Innovation, National Institute of Biomedical Innovation, Health and Nutrition, Osaka 567-0085, Japan.|Laboratory of Vaccine Science, WPI Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan.
authors.forename: Taiki
authors.initials: T
authors.lastname: Aoshi
authors.affiliation: Laboratory of Adjuvant Innovation, National Institute of Biomedical Innovation, Health and Nutrition, Osaka 567-0085, Japan.|Department of Pediatrics, Yokohama City University Graduate School of Medicine, Kanagawa 236-0004, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Ozasa
authors.affiliation: Laboratory of Adjuvant Innovation, National Institute of Biomedical Innovation, Health and Nutrition, Osaka 567-0085, Japan.|Laboratory of Vaccine Science, WPI Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan.
authors.forename: Takato
authors.initials: T
authors.lastname: Kusakabe
authors.affiliation: Laboratory of Adjuvant Innovation, National Institute of Biomedical Innovation, Health and Nutrition, Osaka 567-0085, Japan.|Laboratory of Vaccine Science, WPI Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan.
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Momota
authors.affiliation: Laboratory of Adjuvant Innovation, National Institute of Biomedical Innovation, Health and Nutrition, Osaka 567-0085, Japan.|Laboratory of Vaccine Science, WPI Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan.
authors.forename: Yasunari
authors.initials: Y
authors.lastname: Haseda
authors.affiliation: Laboratory of Adjuvant Innovation, National Institute of Biomedical Innovation, Health and Nutrition, Osaka 567-0085, Japan.|Department of Pediatrics, Yokohama City University Graduate School of Medicine, Kanagawa 236-0004, Japan.
authors.forename: Shingo
authors.initials: S
authors.lastname: Kobari
authors.affiliation: Laboratory of Adjuvant Innovation, National Institute of Biomedical Innovation, Health and Nutrition, Osaka 567-0085, Japan.|Laboratory of Vaccine Science, WPI Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan.
authors.forename: Etsushi
authors.initials: E
authors.lastname: Kuroda
authors.affiliation: Laboratory of Adjuvant Innovation, National Institute of Biomedical Innovation, Health and Nutrition, Osaka 567-0085, Japan.|Laboratory of Vaccine Science, WPI Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan.
authors.forename: Kouji
authors.initials: K
authors.lastname: Kobiyama
authors.affiliation: Laboratory of Malaria Immunology, WPI Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan.
authors.forename: Cevayir
authors.initials: C
authors.lastname: Coban
authors.affiliation: Laboratory of Adjuvant Innovation, National Institute of Biomedical Innovation, Health and Nutrition, Osaka 567-0085, Japan.|Laboratory of Vaccine Science, WPI Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan.
authors.forename: Ken J
authors.initials: KJ
authors.lastname: Ishii
mesh_terms: D000072283:A549 Cells; D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000067531:Alarmins / Q000378:metabolism; D000818:Animals; D000917:Antibody Formation / Q000187:drug effects; D005260:Female; D006801:Humans; D058847:Inflammasomes / Q000378:metabolism; D008055:Lipids / Q000737:chemistry* / Q000494:pharmacology; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009092:Mucous Membrane / Q000187:drug effects* / Q000276:immunology; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein / Q000378:metabolism; D009696:Nucleic Acids / Q000378:metabolism; D012313:RNA / Q000494:pharmacology*; D051195:Toll-Like Receptor 2 / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000378:metabolism
chemical_list: D000276:Adjuvants, Immunologic; D000067531:Alarmins; C000627256:Endocine; D058847:Inflammasomes; D008055:Lipids; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C492716:Nlrp3 protein, mouse; D009696:Nucleic Acids; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D012313:RNA