Mucosal vaccine with adjuvant that activates plasmacytoid dendritic cells

2013 Fiscal Year Final Research Report

• Project/Area Number: 22591105
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Infectious disease medicine
• Research Institution: University of Fukui
• Principal Investigator: IHO Sumiko 福井大学, 医学部, 講師 (80151653)
• Co-Investigator(Kenkyū-buntansha): MAEYAMA Junichi 国立感染症研究所, 血液・安全性研究部, 主任研究官 (40199641) ; TAKEUCHI Kneji 福井大学, 医学部, 助教 (40236419) ; SHIMADA Ichiroh 福井大学, 医学部, 准教授 (20272908)
• Project Period (FY): 2010-04-01 – 2014-03-31
• Keywords: 粘膜ワクチン / アジュバント / CpG oligoDNA / 形質細胞様樹状細胞 / Th1 / 結核ワクチン

Research Abstract

CpG oligoDNAs (ODNs) 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 Th1 immunity through the mucosa, we constructed phosphodiester CpG ODN "G9.1" and investigated its usefulness as mucosal adjuvant.
G9.1 increased Th1 immunity in mice and humans. Nasal vaccination of G9.1 with diphtheria toxoid (DT) to mice induced DT-specific mucosal IgA and serum IgG2a/c (Th1-type). Induction of Th1-type Ab depended on pDCs. Combined immunization with a specific Mycobacterium tuberculosis antigen and G9.1 to a model animal, which exhibits week immunity against Mycobacterium tuberculosis infection, augmented the protective immunity. The increase in G9.1 activity with this antigen may be involved in the mechanisms. G9.1 seems to be a promising mucosal adjuvant.

Research Products

• [Journal Article] A palindromic CpG-containing phosphodiester oligodeoxynucleotides as a mucosal adjuvant stimulates plasmacytoid dendritic cell-mediated TH1 immunity (2014)
  • Author(s): Maeyama JI, Takatsuka H, Suzuki F, Kubota A, Horiguchi S, Komiya T, Shimada I, Murata E, Osawa Y, Kitagawa H, Matsuki T, Yamamoto S, Iho S
  • Journal Title: Plos One Volume: 9巻 Pages: e88846
  • DOI: 10.1371/journal.pone.0088846
  • Peer Reviewed
• [Journal Article] Reactivation of immune responses against Mycobacterium tuberculosis by boosting with the CpG oligomer in aged mice primarily vaccinated with Mycobacterium bovis BCG (2013)
  • Author(s): Taniguchi K, Takii T, Yamamoto S, Maeyama J, Iho S, Maruyama M, Iizuka N, Ozeki Y, Matsumoto S, Hasegawa T, Miyatake Y, Itoh S, Onozaki K
  • Journal Title: Immun Ageing Volume: 10巻 Pages: 25
  • DOI: 10.1186/1742-4933-10-2
  • Peer Reviewed
• [Presentation] 結核菌組換えタンパク質およびTLR9リガンドを用いた結核ブースターワクチンの結核菌噴霧感染による評価 (2014)
  • Author(s): 前山順一、山崎利雄、山本十糸子、林大介、松本壮吉、網康至、須崎百合子、伊保澄子、山本三郎
  • Organizer: 第87回日本細菌学会総会
  • Place of Presentation: 東京
  • Year and Date: 20140326-28
• [Presentation] BCG Tokyo172株のサブポピュレーションBCG-IIを用いた結核ブースターワクチンの評価系の構築とワクチン候補の評価 (2013)
  • Author(s): 前山順一、伊保澄子、岡真優子、井坂雅徳、松本壮吉、山本三郎
  • Organizer: 第86回日本細菌学会総
  • Place of Presentation: 千葉
  • Year and Date: 20130318-20
• [Presentation] 粘膜アジュバントとして新規A型CpG-DNAの作用機構:形質細胞様樹状細胞の関与 (2012)
  • Author(s): 前山順一、伊保澄子、井坂雅徳、山本三郎
  • Organizer: 第85回日本細菌学会
  • Place of Presentation: 長崎
  • Year and Date: 20120328-29
• [Presentation] Immune responses in guinea pig administered with anti-tuberculosis booster vaccine candidate consisting of recombinant proteins of Myco -bacterium tuberculosis and ajuvants, The IUMS 2011 Sapporo Congress (2011)
  • Author(s): Maeyama JI, Iho S, Osada-Oka M, Matsumoto S, Isaka M, Yamamoto S
  • Organizer: International Union of Micro -biological Societies
  • Place of Presentation: Sapporo
  • Year and Date: 20110906-10
• [Presentation] Effects of adjuvants on guinea pig and mouse administered with recombinant proteins derived from Mycobacterium tuberculosis (2011)
  • Author(s): Maeyama JI, Iho S, Matsumoto S, Isaka M, Yamamoto S
  • Organizer: Keystone Symposium. Tuberculosis : Immunology, Cell Biology and Novel Vaccination Strategies
  • Place of Presentation: Vancouver, British Columbia
  • Year and Date: 20110115-20
• [Presentation] Newly-identified phosphodiester CpG -DNA has mucosal adjuvanticity by intranasal administration with diphtheria toxoid (2010)
  • Author(s): Meyama JI, Iho S, Komiyama T, Takahashi M, Matsuki T, Yamamoto S
  • Organizer: 14th International. 14th International Congress of Immunology
  • Place of Presentation: Kobe
  • Year and Date: 20100822-27
• [Book] Japan Anti-Tuber -culosis Association, Tokyo, Unique characteristics of palindromic CpG -oligodeoxynucleotide (2011)
  • Author(s): Iho S, Osawa Y, Takatsuka H, Maeyama J-I, Horiguchi S, Kitagawa H, Yamamoto S
  • Total Pages: 268 (157-176)
  • Publisher: In BCG vaccine and adjuvant (Takii T, Maeyama J-I, and Yamamoto S
• [Book] Japan Anti-Tuberculo -sis Association, Tokyo, Mucosal adju -vants (2011)
  • Author(s): Maeyama J-I
  • Total Pages: 268 (177-192)
  • Publisher: In BCG vaccine and adjuvant (Takii T, Maeyama J-I, and Yamamoto S
• [Patent(Industrial Property Rights)] 免疫刺激G9.1の抗結核ブースターワクチンへの応用 (2011)
  • Inventor(s): 伊保澄子、前山順一、松本壮吉、山本三郎
  • Industrial Property Rights Holder: 福井大学、国立感染症研究所長、大阪市立大学、日本ビーシージー製造株式会社
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 特願2011-080646
  • Filing Date: 2011-03-31
  • Overseas
• [Patent(Industrial Property Rights)] Immunostimulatory oligonucleotide that induces interferon alpha (2010)
  • Inventor(s): Kitagawa H, Iho S, Yamamoto S, Matsuki T
  • Industrial Property Rights Holder: 江守商事株式会社、福井大学
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: US7718623
  • Acquisition Date: 2010-05-18
  • Overseas