title: Advax, a Delta Inulin Microparticle, Potentiates In-built Adjuvant Property of Co-administered Vaccines.
abstract: Advax, a delta inulin-derived microparticle, has been developed as an adjuvant for several vaccines. However, its immunological characteristics and potential mechanism of action are yet to be elucidated. Here, we show that Advax behaves as a type-2 adjuvant when combined with influenza split vaccine, a T helper (Th)2-type antigen, but behaves as a type-1 adjuvant when combined with influenza inactivated whole virion (WV), a Th1-type antigen. In addition, an adjuvant effect was not observed when Advax-adjuvanted WV vaccine was used to immunize toll-like receptor (TLR) 7 knockout mice which are unable to respond to RNA contained in WV antigen. Similarly, no adjuvant effect was seen when Advax was combined with endotoxin-free ovalbumin, a neutral Th0-type antigen. An adjuvant effect was also not seen in tumor necrosis factor (TNF)-α knockout mice, and the adjuvant effect required the presences of dendritic cells (DCs) and phagocytic macrophages. Therefore, unlike other adjuvants, Advax potentiates the intrinsic or in-built adjuvant property of co-administered antigens. Hence, Advax is a unique class of adjuvant which can potentiate the intrinsic adjuvant feature of the vaccine antigens through a yet to be determined mechanism.
authors.affiliation: Laboratory of Adjuvant Innovation, National Institutes of Biomedical Innovation, Health and Nutrition, Osaka 567-0085, Japan; Vaccine Research Development Office, Advanced Drug Research Laboratories, Sohyaku. Innovative Research Division, Mitsubishi Tanabe Pharma Corporation, Yokohama 227-0033, Japan; Laboratory of Vaccine Science, WPI Immunology Frontier Research Centre, Osaka University, Osaka 565-0871, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Hayashi
authors.affiliation: Laboratory of Adjuvant Innovation, National Institutes of Biomedical Innovation, Health and Nutrition, Osaka 567-0085, Japan; Laboratory of Vaccine Science, WPI Immunology Frontier Research Centre, Osaka University, Osaka 565-0871, Japan.
authors.forename: Taiki
authors.initials: T
authors.lastname: Aoshi
authors.affiliation: Laboratory of Adjuvant Innovation, National Institutes of Biomedical Innovation, Health and Nutrition, Osaka 567-0085, Japan; Laboratory of Vaccine Science, WPI Immunology Frontier Research Centre, Osaka University, Osaka 565-0871, Japan.
authors.forename: Yasunari
authors.initials: Y
authors.lastname: Haseda
authors.affiliation: Laboratory of Adjuvant Innovation, National Institutes of Biomedical Innovation, Health and Nutrition, Osaka 567-0085, Japan; Laboratory of Vaccine Science, WPI Immunology Frontier Research Centre, Osaka University, Osaka 565-0871, Japan.
authors.forename: Kouji
authors.initials: K
authors.lastname: Kobiyama
authors.affiliation: Systems Immunology Laboratory, WPI Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan.
authors.forename: Edward
authors.initials: E
authors.lastname: Wijaya
authors.affiliation: Toxicogenomics-informatics Project, National Institutes of Biomedical Innovation, Health and Nutrition, Osaka 567-0085, Japan.
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Nakatsu
authors.affiliation: Toxicogenomics-informatics Project, National Institutes of Biomedical Innovation, Health and Nutrition, Osaka 567-0085, Japan.
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Igarashi
authors.affiliation: Systems Immunology Laboratory, WPI Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan.
authors.forename: Daron M
authors.initials: DM
authors.lastname: Standley
authors.affiliation: Toxicogenomics-informatics Project, National Institutes of Biomedical Innovation, Health and Nutrition, Osaka 567-0085, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yamada
authors.affiliation: Vaxine Pty Ltd., Bedford Park, Adelaide, Australia.
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Honda-Okubo
authors.affiliation: Division of Molecular and Cellular Immunoscience, Department of Biomolecular Sciences, Faculty of Medicine, Saga University, Saga 849-8501, Japan; Department of Immunology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8544, Japan.
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Hara
authors.affiliation: Laboratory for Cell Signaling, RIKEN Center for Integrative Medical Sciences, Yokohama 230-0045, Japan; jWPI Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Saito
authors.affiliation: Department of Experimental Immunology, Institute of Development, Aging and Cancer, Tohoku University, Sendai 980-8575, Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Takai
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: Vaxine Pty Ltd., Bedford Park, Adelaide, Australia; Department of Diabetes and Endocrinology, Flinders Medical Centre, Flinders University, Adelaide 5042, Australia.
authors.forename: Nikolai
authors.initials: N
authors.lastname: Petrovsky
authors.affiliation: Laboratory of Adjuvant Innovation, National Institutes of Biomedical Innovation, Health and Nutrition, Osaka 567-0085, Japan; Laboratory of Vaccine Science, WPI Immunology Frontier Research Centre, Osaka University, Osaka 565-0871, Japan. Electronic address: kenishii@biken.osaka-u.ac.jp.
authors.forename: Ken J
authors.initials: KJ
authors.lastname: Ishii
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000818:Animals; D000941:Antigens / Q000276:immunology; D015415:Biomarkers; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D005260:Female; D007114:Immunization; D007444:Inulin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D008081:Liposomes; D008213:Lymphocyte Activation; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D023421:Models, Animal; D010587:Phagocytosis / Q000276:immunology; D015398:Signal Transduction; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism; D014612:Vaccines / Q000008:administration & dosage* / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D000941:Antigens; D015415:Biomarkers; D016207:Cytokines; D008081:Liposomes; D014612:Vaccines; C576871:delta inulin; D007444:Inulin
keywords: Adjuvant; Inulin; Macrophage; Particle; Vaccine