Development of next-generation dengue virus vaccine

• Project/Area Number: 23580422
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Applied veterinary science
• Research Institution: Osaka University (2012-2013); Kyoto University (2011)
• Principal Investigator: KOBAYASHI Takeshi 大阪大学, 微生物病研究所, 特任准教授 (90324847)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2011: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: デングウイルス / ワクチン / デング熱 / サル

Research Abstract

To develop a new DNA vaccine for dengue virus (DV) infection, we have constructed a plasmid-based infectious clone encoding full-length DV-1 cDNA under control of the minimum cytomegalovirus promoter. In our experiments, yields of WT virus 24 hours after plasmid transfection are regularly in the range of 100 to 1000 PFU/ml. Furthermore, DV-1 reporter replicon with luciferase was made by replacing part of the DV-1 structural gene region with the luciferase gene.
To improve the reverse genetics for DV, we have developed a homologous recombination-based reverse genetics for DV. Furthermore, we have rescued a chimeric DV, which expresses the prM and E genes from DV type 2 in a DV type 1 genetic background.
These improved infectious cDNA clone and reporter replicon systems described here can be employed for studies of the DV replication and pathogenesis and used to develop vaccines, diagnostics, and therapeutics.

Research Products

• [Journal Article] Imported case of acute respiratory tract infection associated with a member of species Nelson Bay orthoreovirus (2014)
  • Author(s): Yamanaka A., Iwakiri A., Yoshikawa T., Sakai K., Harpal S., Himeji D., Kikuchi I., Ueda1 A., Yamamoto S., Miura M., Shioyama Y., Kawano K., Nagaishi T., Saito M., Minomo M., Iwamoto N., Hidaka Y., Sohma H., Kobayashi T., Kanai Y., Kawagishi T., Nagata N., Fukushi S., Mizutani T., Tani H., Taniguchi S., Fukuma A., Shimojima M., Kurane I., Kageyama T., Odagiri T., Saijo M., and Morikawa S.
  • Journal Title: PLoS One Volume: 9
  • Peer Reviewed
• [Journal Article] A plasmid-based reverse genetics system for mammalian orthoreoviruses driven by a plasmid-encoded T7 RNA polymerase (2014)
  • Author(s): Komoto S., Kawagishi T., Kobayashi T., Ikizler M., Iskarpatyoti J., Dermody T. S., and Taniguchi K.
  • Journal Title: J . Virol. Methods Volume: 196 Pages: 36-39
  • Peer Reviewed
• [Journal Article] A plasmid-based reverse genetics system for mammalian orthoreoviruses driven by a plasmid-encoded T7 RNA polymerase (2014)
  • Author(s): Satoshi Komoto
  • Journal Title: Journal of Virological Methods Volume: 196 Pages: 36-39
  • DOI: 10.1016/j.jviromet.2013.10.023
  • Peer Reviewed
• [Journal Article] Imported case of acute respiratory tract infection associated with a member of species nelson bay orthoreovirus (2014)
  • Author(s): Atsushi Yamanaka
  • Journal Title: PLoS One Volume: ９ Issue: 3 Pages: e92777-e92777
  • DOI: 10.1371/journal.pone.0092777
  • Peer Reviewed / Open Access
• [Journal Article] Nonstructural Proteinσ1s Mediates Reovirus-Induced Cell Cycle Arrest and Apoptosis (2013)
  • Author(s): Boehme K. W., Hammer K., Tollefson W. C., Konopka-Anstadt J. L., Kobayashi T., and Dermody T. S.
  • Journal Title: J . Virol Volume: 87 Pages: 12967-12979
  • Peer Reviewed
• [Journal Article] Natural infection of cynomolgus monkeys with dengue virus occurs in epidemic cycles in the Philippines (2013)
  • Author(s): Kato F., Ishida Y., Kawagishi T., Kobayashi T., Hishiki T., Miura T., and Igarashi T.
  • Journal Title: J . Gen. Virol Volume: 94 Pages: 2202-2207
  • Peer Reviewed
• [Journal Article] Construction and characterization of an infectious molecular clone of Koala retrovirus (2013)
  • Author(s): Shojima T., Hoshino S., Abe M., Yasuda J., Shogen H., Kobayashi T., and Miyazawa T.
  • Journal Title: J . Virol Volume: 87 Pages: 5081-5088
  • Peer Reviewed
• [Journal Article] Generation of a replication-competent chimeric simian-human immunodeficiency virus carrying env from subtype C clinical isolate through intracellular homologous recombination (2013)
  • Author(s): Fujita Y, Otsuki H., Watanabe Y., Yasui M., Kobayashi T., Miura T., and Igarashi T.
  • Journal Title: Virology Volume: 436 Pages: 100-111
  • NAID: 120005434974
  • Peer Reviewed
• [Journal Article] Natural infection of cynomolgus monkeys with dengue virus occurs in epidemic cycles in the Philippines (2013)
  • Author(s): Fumihiro Kato
  • Journal Title: Journal of General Virology Volume: 94 Issue: 10 Pages: 2202-2207
  • DOI: 10.1099/vir.0.055343-0
  • Peer Reviewed
• [Journal Article] Nonstructural protein σ1s mediates reovirus-induced cell cycle arrest and apoptosis (2013)
  • Author(s): Karl W. Boehme
  • Journal Title: Journal of Virology Volume: 87 Issue: 23 Pages: 12967-12979
  • DOI: 10.1128/jvi.02080-13
  • Peer Reviewed
• [Journal Article] Construction and characterization of an infectious molecular clone of koala retrovirus (2013)
  • Author(s): Takayuki Shojima
  • Journal Title: Journal of Virology Volume: 87 Issue: 9 Pages: 5081-5088
  • DOI: 10.1128/jvi.01584-12
  • Peer Reviewed
• [Journal Article] Binding of transcription factor activating protein 2γon the 5'-proximal promoter region of human porcine endogenous retrovirus subgroup A receptor 2/GPR172B (2012)
  • Author(s): Nakaya Y, Shimode S., Kobayashi T., Imakawa K., and Miyazawa T.
  • Journal Title: Xenotransplantation Volume: 19 Pages: 177-185
  • Peer Reviewed
• [Journal Article] Sequence comparison of three infectious molecular clones of RD-114 virus (2012)
  • Author(s): Shimode S, Yoshikawa R., Hoshino S., Nakaya Y., Sakaguchi S., Kobayashi T., and Miyazawa T.
  • Journal Title: Virus Genes Volume: 45 Pages: 393-397
  • Peer Reviewed
• [Journal Article] Canine ASCT1 and ASCT2 are functional receptors for RD-114 virus in dogs (2012)
  • Author(s): Yoshikawa R, Yasuda J., Kobayashi T., and Miyazawa T.
  • Journal Title: J . Gen. Virol Volume: 93 Pages: 603-607
  • Peer Reviewed
• [Journal Article] Identification and characterization of feline UBE1L gene (2012)
  • Author(s): Shimode S, Miyazawa T., Kobayashi T., Sato H., and Tanabe T.
  • Journal Title: J . Vet. Med. Sci Volume: 74 Pages: 235-239
  • NAID: 130001033063
  • Peer Reviewed
• [Journal Article] Lymphatic tissues harbor viral reservoirs that cause rebound of plasma viremia in SIV-infected macaques upon cessation of combined antiretroviral therapy (2012)
  • Author(s): Horiike M., Iwami S., Sato A., Watanabe Y., Yasui M., Kobayashi T., Miura T., and Igarashi T.
  • Journal Title: Virology Volume: 423 Pages: 107-118
  • Peer Reviewed
• [Journal Article] Binding of transcription factor activating protein 2 γ on the 5′-proximal promoter region of human porcine endogenous retrovirus subgroup A receptor 2/GPR172B (2012)
  • Author(s): Yuki Nakaya
  • Journal Title: Xenotransplantation Volume: 19 Issue: 3 Pages: 177-185
  • DOI: 10.1111/j.1399-3089.2012.00701.x
  • Peer Reviewed
• [Journal Article] Lymph nodes harbor viral reservoirs that cause rebound of plasma viremia in SIV-infected macaques upon cessation of combined antiretroviral therapy (2012)
  • Author(s): Mariko Horiike
  • Journal Title: Virology Volume: 423 Pages: 107-118
  • Peer Reviewed
• [Journal Article] Identification and characterization of feline UBE1L gene (2012)
  • Author(s): Sayumi Shimode
  • Journal Title: Journal of Veterinary Medical Science Volume: 74 Pages: 235-239
  • Peer Reviewed
• [Journal Article] Canine ASCT1 and ASCT2 are functional receptors for RD-114 virus in dogs (2012)
  • Author(s): Rokusuke Yoshikawa
  • Journal Title: Journal of General Virology Volume: 93 Pages: 603-607
  • Peer Reviewed
• [Journal Article] The reovirusσ1s protein is a determinant of hematogenous but not neural viral dissemination in mice (2011)
  • Author(s): Boehme K. W., Frierson J. M., Konopka J. L., Kobayashi T., and Dermody T. S.
  • Journal Title: J . Virol Volume: 85 Pages: 11781-11790
  • Peer Reviewed
• [Journal Article] Reverse genetics for mammalian reovirus (2011)
  • Author(s): Boehme K. W., Ikizler M., Kobayashi T., and Dermody T. S.
  • Journal Title: Methods Volume: 55 Pages: 109-113
  • Peer Reviewed
• [Journal Article] Crystal structure of reovirus attachment protein sigma1 in complex with sialylated oligosacchrides (2011)
  • Author(s): Reiter D. M., Frierson J. M., Halvorson E. E., Kobayashi T., Dermody T. S., and Stehle T.
  • Journal Title: PLoS Pathogen Volume: 7
  • Peer Reviewed
• [Journal Article] Crystal structure of reovirus attachment protein σ1 in complex with sialylated oligosaccharides (2011)
  • Author(s): Dirk M. Reiter
  • Journal Title: Plos Pathogens Volume: 7
  • Peer Reviewed
• [Journal Article] The reovirus sigma1s protein is a determinant of hematogenous but not neural virus dissemination in mice (2011)
  • Author(s): Karl W. Boehme
  • Journal Title: Journal of Virology Volume: 85 Pages: 11781-11790
  • Peer Reviewed
• [Presentation] 分泌型ルシフェラーゼ遺伝子を有するデングウイルス1型レプリコンの構築 (2013)
  • Author(s): 加藤文博, 他
  • Organizer: 第61回日本ウイルス学会学術集会
  • Place of Presentation: 神戸
• [Presentation] フィリピンカニクイザルにおけるデングウイルス自然感染 (2013)
  • Author(s): 石田祐樹, 他
  • Organizer: 第61回日本ウイルス学会学術集会
  • Place of Presentation: 神戸
• [Presentation] フィリピンカニクイザルにおけるデングウイルス自然感染 (2013)
  • Author(s): 石田祐樹
  • Organizer: 第61回日本ウイルス学会
  • Place of Presentation: 神戸国際会議場
• [Presentation] 分泌型ルシフェラーゼ遺伝子を有するデングウイルス1型レプリコンの構築 (2013)
  • Author(s): 加藤文博
  • Organizer: 第61回日本ウイルス学会
  • Place of Presentation: 神戸国際会議場
• [Presentation] コアラレトロウイルス内在化機序の解析 (2012)
  • Author(s): 星野重樹, 他
  • Organizer: 第60回日本ウイルス学会学術集会
  • Place of Presentation: 大阪
• [Presentation] ウシ内在性レトロウイルス-K1の獲得によるウシ科動物の進化 (2012)
  • Author(s): 仲屋友喜, 他
  • Organizer: 第60回日本ウイルス学会学術集会
  • Place of Presentation: 大阪
• [Presentation] シベリア型ダニ媒介性脳炎ウイルスIR99-2f7株の感染性cDNAクローンの構築 (2012)
  • Author(s): 川岸崇裕, 他
  • Organizer: 第60回日本ウイルス学会学術集会
  • Place of Presentation: 大阪
• [Presentation] 抗デングウイルス活性を有する化合物の探索および作用機序の解析 (2012)
  • Author(s): 加藤文博, 他
  • Organizer: 第60回日本ウイルス学会学術集会
  • Place of Presentation: 大阪
• [Presentation] 中和感受性を増強する薬剤による抗HIV-1治療戦略に向けた新規SHIV/アカゲザルモデルの開発 (2012)
  • Author(s): 大附寛幸, 他
  • Organizer: 第60回日本ウイルス学会学術集会
  • Place of Presentation: 大阪
• [Presentation] 中和感受性を増強する薬剤による抗 HIV-1 治療戦略に向けた新規 SHIV/アカゲザル評価モデ (2012)
  • Author(s): 大附 寛幸
  • Organizer: 第60回日本ウイルス学会学術集会
  • Place of Presentation: 大阪
• [Presentation] フラビウイルスにおける宿主DNA修復機構を用いた新規リバースジェネティクス系の開発 (2011)
  • Author(s): 日向亮輔, 他
  • Organizer: 第18回トガ・フラビ・ペスチウイルス研究会
  • Place of Presentation: 東京
  • Year and Date: 2011-11-11
• [Presentation] ダニ媒介性脳炎ウイルスIR99株の感染性cDNAクローンの構築 (2011)
  • Author(s): 川岸崇裕, 他
  • Organizer: 第18回トガ・フラビ・ペスチウイルス研究会
  • Place of Presentation: 東京
  • Year and Date: 2011-11-11
• [Presentation] 抗デングウイルス活性を有する薬剤の探索 (2011)
  • Author(s): 加藤文博, 他
  • Organizer: 第18回トガ・フラビ・ペスチウイルス研究会
  • Place of Presentation: 東京
  • Year and Date: 2011-11-11
• [Presentation] 中和抵抗性のサル/ヒト免疫不全ウイルスの作製とin vitroにおける立体構造変化誘導剤による中和感受性増強効果の評価 (2011)
  • Author(s): 大附寛幸, 他
  • Organizer: 第25回日本エイズ学会学術集会
  • Place of Presentation: 東京
• [Presentation] ウシ内在性レトロウイルスK1エンベロープタンパクの開裂に重要な領域の探索 (2011)
  • Author(s): 仲屋友喜, 他
  • Organizer: 第152回日本獣医学会学術集会
  • Place of Presentation: 大阪
• [Presentation] 新規相同組換え技術による組換えダニ媒介性脳炎ウイルスの構築 (2011)
  • Author(s): 川岸崇裕, 他
  • Organizer: 第152回日本獣医学会学術集会
  • Place of Presentation: 大阪
• [Presentation] 中和抵抗性のサル/ヒト免疫不全ウイルスの作製とin vitro における立体構造変化誘導剤による中和感受性増強効果の評価 (2011)
  • Author(s): 大附寛幸
  • Organizer: 第25回日本エイズ学会学術集会
  • Place of Presentation: 東京
• [Remarks]
  • URL: http://www.biken.osaka-u.ac.jp/lab/viral-replication/