Development of the novel therapeutic vaccine using persistent viral hepatitis infection model

2013 Fiscal Year Final Research Report

• Project/Area Number: 23591004
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Tokyo Metropolitan Institute of Medical Science
• Principal Investigator: KIMURA Kiminori 公益財団法人東京都医学総合研究所, ゲノム医科学研究分野, 研究員 (70397339)
• Co-Investigator(Kenkyū-buntansha): NAGAKI Masahito 岐阜大学, 医学部, 非常勤講師 (30293559)
• Project Period (FY): 2011 – 2013
• Keywords: HCV / ワクチン

Research Abstract

Chronic hepatitis C, which is caused by infection with the hepatitis C virus (HCV), is a global health problem. Using a mouse model of hepatitis C, we examined the therapeutic effects of a recombinant vaccinia virus (rVV) that encodes an HCV protein. Immunization with one rVV strain (rVV-N25), which encoded nonstructural HCV proteins, suppressed serum inflammatory cytokine levels and alleviated the symptoms of pathological chronic hepatitis C within 7 days after injection. Furthermore, HCV protein levels in liver tissue also decreased in a CD4 and CD8 T-cell-dependent manner. Consistent with these results, we showed that rVV-N25 immunization induced a robust CD8 T-cell immune response that was specific to the HCV nonstructural protein 2. In addition, we propose that rVV-N25 could be developed as an effective therapeutic vaccine.

Research Products

• [Journal Article] Kinetics of peripheral hepatitis B virus-specific CD8+ T cells in patients with onset of viral reactivation (2013)
  • Author(s): Aoki J, Kowazaki Y, Ohtsuki T, Okamoto R, Ohashi K, Hayashi S, Sakamaki H, Kohara M, Kimura K.
  • Journal Title: J Gastroenterol Volume: Jun;48(6)(Epub 2012 Sep 26) Pages: 728-37
  • DOI: 10.1007/s00535-012-0676-y
  • Peer Reviewed
• [Journal Article] Immunization with a recombinant vaccinia virus that encodes nonstructural proteins of the hepatitis C virus suppresses viral protein levels in mouse liver (2012)
  • Author(s): Sekiguchi S, Kimura K, Chiyo T, Ohtsuki T, Tobita Y, Tokunaga Y, Yasui F, Tsukiyama-Kohara K, Wakita T, Tanaka T, Miyasaka M, Mizuno K, Hayashi Y, Hishima T, Matsushima K, Kohara M.
  • Journal Title: PLoS One Volume: 7(12) Pages: e51656
  • DOI: 10.1371
  • Peer Reviewed
• [Journal Article] The development of therapeutic vaccine for hepatitis C virus (2012)
  • Author(s): Kimura K, Kohara M. Gan To Kagaku Ryoho.
  • Journal Title: Review Volume: Oct;39(10) Pages: 1451-7
  • Peer Reviewed
• [Journal Article] An experimental mouse model for hepatitis C virus (2011)
  • Author(s): Kimura K, Kohara M.
  • Journal Title: Exp Anim Volume: 60(2) Pages: 93-100
  • Peer Reviewed
• [Journal Article] Role of interleukin-18 in intrahepatic inflammatory cell recruitment in acute liver injury (2011)
  • Author(s): Kimura K, Sekiguchi S, Hayashi S, Hayashi Y, Hishima T, Nagaki M, Kohara M.
  • Journal Title: J Leukoc Biol Volume: Mar;89(3) Pages: 433-42
  • DOI: 10.1189/jlb.0710412
  • Peer Reviewed
• [Presentation] The efficac y of entecavir in patients with hepatitis B viru s reactivation after allo-HSCT (2013)
  • Author(s): Yoshioka K, Kimura K, et al.
  • Organizer: 第75回日本血液学会学術集会、Poster presentation PS-1 -374
  • Place of Presentation: 札幌
  • Year and Date: 2013-11-09
• [Presentation] 造血幹細胞移植後のHBV再活性化における宿主の免疫応答の解析 (2013)
  • Author(s): 木村公則、坂巻壽他
  • Organizer: 第17回日本肝臓学会大会
  • Place of Presentation: 東京
  • Year and Date: 2013-10-09
• [Presentation] Ki netics of peripheral hepatitis B virus-specific C D8+ T cells in patients with onset of viral rea ctivation. Poster presentation (2013)
  • Author(s): Kimura K, Aoki J, Kowazaki Y, et al.
  • Organizer: AASLD (Americ an Association for the study of Liver Disease s) Single topic Conference
  • Place of Presentation: Washington DC
  • Year and Date: 2013-03-21