Development of novel norovirus vaccine using rotavirus-based mucosal vector

• Project/Area Number: 18K19444
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 49:Pathology, infection/immunology, and related fields
• Research Institution: Osaka University
• Principal Investigator: Kobayashi Takeshi 大阪大学, 微生物病研究所, 准教授 (90324847)
• Project Period (FY): 2018-06-29 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000); Fiscal Year 2019: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000); Fiscal Year 2018: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
• Keywords: ノロウイルス / ロタウイルス / ワクチン

Outline of Final Research Achievements

Human noroviruses are a leading cause of gastroenteritis outbreaks worldwide. Live-attenuated and inactivated norovirus vaccines have not been pursued due to the lack of a robust norovirus cell culture system. In this study, we aimed to develop norovirus vaccine using rotavirus-based vaccine vector. We first generated stable reporter rotaviruses expressing luciferase and green fluorescent proteins. Using the stable rotavirus reporter expression systems, we generated a recombinant rotavirus expressing norovirus VP1 gene derived from GII.4 strain. Expression of VP1 was clearly observed in cells infected with rotavirus expressing VP1 gene. These results demonstrate the utility of rotavirus as a mucosal vaccine vector against enteric pathogens including norovirus.

Academic Significance and Societal Importance of the Research Achievements

ヒトノロウイルスでは効率の良い細胞培養系の開発が遅れており、ワクチンも開発されていない。現在、ノロウイルス様粒子（VLP）がワクチン候補として開発が進んでいる。本研究では、ノロウイルスVLPを発現するロタウイルスを開発し、ノロウイルスおよびロタウイルスに対する２価ワクチンの開発を目的とした。本研究において、安定的にレポーター遺伝子やノロウイルスVP1遺伝子を発現するロタウイルスベクターの開発に成功した。これらの成果はノロウイルスワクチンの開発だけでなく、他の消化器感染症に対するワクチン開発にも有用と考えられ、社会的意義も高い。

Research Products

• [Journal Article] Reverse Genetics System for a Human Group A Rotavirus. (2020)
  • Author(s): Kawagishi T, Nurdin J, Onishi M, Nouda R, Kanai Y, Tajima T, Ushijima H, Kobayashi T
  • Journal Title: J Virol Volume: 94 Issue: 2
  • DOI: 10.1128/jvi.00963-19
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Cell-cell fusion induced by reovirus FAST proteins enhances replication and pathogenicity of non-enveloped dsRNA viruses. (2019)
  • Author(s): 1.Kanai Y, Kawagishi T, Sakai Y, Nouda R, Shimojima M, Saijo M, Matsuura Y, Kobayashi T.
  • Journal Title: PLoS Pathog. Volume: 15 Issue: 4 Pages: e1007675-e1007675
  • DOI: 10.1371/journal.ppat.1007675
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] In Vivo Live Imaging of Oncolytic Mammalian Orthoreovirus Expressing NanoLuc Luciferase in Tumor Xenograft Mice (2019)
  • Author(s): Kanai Yuta、Kawagishi Takahiro、Matsuura Yoshiharu、Kobayashi Takeshi
  • Journal Title: Journal of Virology Volume: 93 Issue: 14
  • DOI: 10.1128/jvi.00401-19
  • Peer Reviewed / Open Access
• [Journal Article] Development of Stable Rotavirus Reporter Expression Systems (2019)
  • Author(s): Kanai Y, Kawagishi T, Nouda R, Onishi M, Pannacha P, Nurdin JA, Nomura K, Matsuura Y, Kobayashi T.
  • Journal Title: Journal of Virology Volume: 93 Issue: 4
  • DOI: 10.1128/jvi.01774-18
  • Peer Reviewed
• [Presentation] Reverse Genetics System for a Human Group A Rotavirus (2020)
  • Author(s): Kawagishi T, Nurdin A, Onishi M, Nouda R, Kanai Y, Tajima T, Ushijima H, Kobayashi T.
  • Organizer: U.S.-Japan Cooperative Medical Sciences Program's 22nd International Conference on Emerging Infectious Diseases in the Pacific Rim
  • Int'l Joint Research
• [Presentation] The Application of Reverse Genetics Systems in Studies of dsRNA Virus Replication and Pathogenesis (2019)
  • Author(s): Kobayashi T.
  • Organizer: Gordon Research Conference Viruses and Cells
  • Int'l Joint Research / Invited
• [Presentation] Reverse Genetic System for Human Rotavirus A Odelia strain (2019)
  • Author(s): Nurdin J, Kawagishi T, Onishi M, Kanai Y, Tajima T, Ushijima H, Kobayashi T.
  • Organizer: The 18th Awaji International Forum on Infection and Immunity
• [Presentation] ロタウイルス NSP3タンパク質のeIF4G結合領域変異がウイルス複製に及ぼす影響 (2019)
  • Author(s): 納田遼太郎, 金井祐太, 川岸崇裕, Pannacha Pimfhun, 小林剛
  • Organizer: 第67回日本ウイルス学会学術集会
• [Presentation] Reverse Genetic System for Human Rotavirus A Odelia strain (2019)
  • Author(s): Nurdin J, Kawagishi T, Onishi M, Kanai Y, Tajima T, Ushijima H, Kobayashi T.
  • Organizer: 第67回日本ウイルス学会学術集会
• [Presentation] ロタウイルスベクターの開発 (2019)
  • Author(s): 金井祐太, 川岸崇裕, Pannacha Pimfhun , 納田遼太郎, 大西未沙, Nurdin Jeffry, 野村圭一郎, Tina Luciany, 山﨑萌子, 小林剛
  • Organizer: 第67回日本ウイルス学会学術集会
• [Presentation] ロタウイルス人工合成法の開発と新規ワクチン (2018)
  • Author(s): Kobayashi T.
  • Organizer: 第22回日本ワクチン学会学術集会
  • Invited
• [Presentation] Nelson Bay reovirus σC body domain is associated with strain-specific differences in viral replication (2018)
  • Author(s): Kawagishi T, Kanai Y, Sakai Y, Nouda R, Tani H, Shimojima M, Saijo M, Matsuura Y, Kobayashi T.
  • Organizer: 第66回日本ウイルス学会学術集会
• [Presentation] Platform for rotavirus vaccine development using plasmid-based reverse genetics (2018)
  • Author(s): Kanai Y, Kawagishi T, Onishi M, Pannacha P, Nouda R, Nurdin J, Nomura K, Ushijima H, Kobayashi T.
  • Organizer: 第66回日本ウイルス学会学術集会
• [Presentation] Fusogenic bat-borne orthoreovirus p17 protein regulates viral replication in a host-specific manner (2018)
  • Author(s): Nouda R, Kawagishi T, Kanai Y, Shimojima M, Saijo M, Matsuura Y, Kobayashi T.
  • Organizer: 第66回日本ウイルス学会学術集会
• [Presentation] Development of stable reporter rotaviruses (2018)
  • Author(s): Pannacha P, Kanai Y, Onishi M, Kawagishi T, Nouda R, Nurdin J, Matsuura Y, Kobayashi T.
  • Organizer: 第66回日本ウイルス学会学術集会
• [Presentation] Reverse genetics systems for orthoreoviruses and rotaviruses (2018)
  • Author(s): Kobayashi T.
  • Organizer: 13th International dsRNA Symposium 2018
  • Int'l Joint Research / Invited
• [Presentation] Antigenicity of simian and human reassortant rotaviruses generated by reverse genetics (2018)
  • Author(s): Kanai Y, Kawagishi T, Onishi M, Pannacha P, Nouda R, Nurdin J, Nomura K, Ushijima H, Kobayashi T.
  • Organizer: 13th International dsRNA Symposium 2018
  • Int'l Joint Research
• [Presentation] Nelson Bay Orthoreovirus cell attachment protein σC determines strain-specific differences in viral replication and pathogenesis (2018)
  • Author(s): Kawagishi T, Kanai Y, Yusuke Sakai, Nouda R,Tani H, Shimojima M, Saijo M, Matsuura Y, Kobayashi T.
  • Organizer: 13th International dsRNA Symposium 2018
  • Int'l Joint Research
• [Presentation] 次世代組換えロタウイルスワクチン作製の試み (2018)
  • Author(s): 金井 祐太、川岸 崇裕、Pimfhun Pannacha、納田 遼太郎、Nurdin Jeffery、野村 圭一郎、牛島 廣治、小林 剛
  • Organizer: 第161回日本獣医学会学術集会
• [Presentation] Nelson Bay orthoreovirus p17 protein regulates viral replication in a host-specific manner (2018)
  • Author(s): Kobayashi T.
  • Organizer: 第12回日中国際ウイルス学会
  • Int'l Joint Research
• [Book] 腎と透析 (2018)
  • Author(s): 小林 剛
  • Total Pages: 3
  • Publisher: 東京医学社
• [Book] 獣医畜産新報 (2018)
  • Author(s): 川岸 崇裕
  • Total Pages: 7
  • Publisher: 文永堂出版