title: A palindromic CpG-containing phosphodiester oligodeoxynucleotide as a mucosal adjuvant stimulates plasmacytoid dendritic cell-mediated T(H)1 immunity.
abstract: BACKGROUND
  CpG oligodeoxynucleotides (ODNs), resembling bacterial DNA, are currently tested in clinical trials as vaccine adjuvants. They have the nuclease-resistant phosphorothioate bond; the immune responses elicited differ according to the CpG ODN sequence and vaccination method. To develop a CpG ODN that can induce plasmacytoid dendritic cell (pDC)-mediated T(H)1 immunity through the mucosa, we constructed phosphodiester G9.1 comprising one palindromic CpG motif with unique polyguanosine-runs that allows degradation similar to naturally occurring bacterial DNA.
  
  
  METHODS
  T(H)1 and T(H)2 immunity activation was evaluated by cytokine production pattern and T-bet/GATA-3 ratio in human peripheral blood mononuclear cells and mouse bone marrow cells. Adjuvanticity was evaluated in mice administered G9.1 with diphtheria toxoid (DT) through nasal vaccination.
  
  
  RESULTS
  G9.1 exhibited stronger IFN-α-inducing activity than A-class CpG ODN2216 and increased T-bet/GATA-3 ratio by enhancing T-bet expression. Nasally administered G9.1 plus DT induced DT-specific mucosal IgA and serum IgG, but not IgE, responses with antitoxin activity in C57BL/6 and BALB/c mice, possibly due to IFN/BAFF production. Induction of T(H)1, but not T(H)2-type Abs depended completely on pDCs, the first in vivo demonstration by CpG ODNs.
  
  
  CONCLUSIONS
  G9.1 is a promising mucosal adjuvant for induction of pDC-mediated T(H)1 immunity.
authors.affiliation: Department of Safety Research on Blood and Biological Products, National Institute of Infectious Diseases, Musashimurayama-shi, Tokyo, Japan.
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Maeyama
authors.affiliation: Division of Legal Medicine, Niigata University Graduate School of Medicine and Dental Sciences, Niigata-shi, Niigata, Japan.
authors.forename: Hisakazu
authors.initials: H
authors.lastname: Takatsuka
authors.affiliation: Department of Ophthalmology, Faculty of Medical Science, University of Fukui, Yoshida-gun, Fukui, Japan.
authors.forename: Fumiko
authors.initials: F
authors.lastname: Suzuki
authors.affiliation: Laboratory of Host Defense, Faculty of Medical Sciences, University of Fukui, Yoshida-gun, Fukui, Japan.
authors.forename: Ayumi
authors.initials: A
authors.lastname: Kubota
authors.affiliation: Department of Anatomy and Neuroscience, Faculty of Medical Sciences, University of Fukui, Yoshida-gun, Fukui, Japan.
authors.forename: Satomi
authors.initials: S
authors.lastname: Horiguchi
authors.affiliation: Department of Bacterial Pathogenesis and Infection, National Institute of Infectious Diseases, Musashimurayama-shi, Tokyo, Japan.
authors.forename: Takako
authors.initials: T
authors.lastname: Komiya
authors.affiliation: Forensic Medicine and Human Genetics, Faculty of Medical Sciences, University of Fukui, Yoshida-gun, Fukui, Japan ; Research and Education Program for Life Science and Translational Research Program, University of Fukui, Fukui-shi, Fukui, Japan.
authors.forename: Ichiroh
authors.initials: I
authors.lastname: Shimada
authors.affiliation: Anesthesiology and Reanimatology, Faculty of Medical Sciences, University of Fukui, Yoshida-gun, Fukui, Japan.
authors.forename: Eri
authors.initials: E
authors.lastname: Murata
authors.affiliation: Otorhinolaryngology-Head and Neck Surgery, Faculty of Medical Sciences, University of Fukui, Yoshida-gun, Fukui, Japan.
authors.forename: Youko
authors.initials: Y
authors.lastname: Osawa
authors.affiliation: Chemical Substances Management, Administration Control Office, Emori & Co., Ltd., Fukui-shi, Fukui, Japan.
authors.forename: Harukazu
authors.initials: H
authors.lastname: Kitagawa
authors.affiliation: Forensic Medicine and Human Genetics, Faculty of Medical Sciences, University of Fukui, Yoshida-gun, Fukui, Japan ; Research and Education Program for Life Science and Translational Research Program, University of Fukui, Fukui-shi, Fukui, Japan.
authors.forename: Takasumi
authors.initials: T
authors.lastname: Matsuki
authors.affiliation: Department of Microbiology, Nagoya City University Medical School, Nagoya-shi, Aichi, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Isaka
authors.affiliation: Central Laboratory, Japan BCG Laboratory, Kiyose-shi, Tokyo, Japan.
authors.forename: Saburo
authors.initials: S
authors.lastname: Yamamoto
authors.affiliation: Laboratory of Host Defense, Faculty of Medical Sciences, University of Fukui, Yoshida-gun, Fukui, Japan ; Research and Education Program for Life Science and Translational Research Program, University of Fukui, Fukui-shi, Fukui, Japan.
authors.forename: Sumiko
authors.initials: S
authors.lastname: Iho
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000277:Adjuvants, Pharmaceutic / Q000494:pharmacology*; D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects / Q000276:immunology; D004269:DNA, Bacterial / Q000276:immunology; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology*; D004168:Diphtheria Toxoid / Q000276:immunology; D005260:Female; D006801:Humans; D016898:Interferon-alpha / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009092:Mucous Membrane / Q000187:drug effects / Q000276:immunology*; D009838:Oligodeoxyribonucleotides / Q000276:immunology*; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D000277:Adjuvants, Pharmaceutic; C408982:CPG-oligonucleotide; D004269:DNA, Bacterial; D004168:Diphtheria Toxoid; D016898:Interferon-alpha; D009838:Oligodeoxyribonucleotides