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Development of novel mucosal vaccines using reovirus vectors

Research Project

Project/Area Number 21K19379
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 49:Pathology, infection/immunology, and related fields
Research InstitutionOsaka University

Principal Investigator

Kobayashi Takeshi  大阪大学, 微生物病研究所, 教授 (90324847)

Project Period (FY) 2021-07-09 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2022: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2021: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Keywordsレオウイルス / ワクチン / ワクチンベクター
Outline of Research at the Start

哺乳類オルソレオウイルス(MRV)は、ヒトに対して安全性が高いこと、高力価のウイルス調整が容易であること、粘膜免疫誘導能を有すること等、粘膜ワクチンベクターとして優れた特性を有している。本研究では、MRV遺伝子改変技術を駆使することで、ノロウイルスおよび新型コロナウイルスを対象とした消化器および呼吸器感染症に対する粘膜ワクチンの開発基盤の確立を目的とする。

Outline of Final Research Achievements

The aim of this project is to develop mucosal vaccines against the novel coronavirus (SARS-CoV-2), which has had a significant impact on the global economy, and norovirus (NV), which causes acute gastroenteritis, using mammalian reoviruses (MRVs). We generated recombinant MRV by inserting the receptor-binding domain of the SARS-CoV-2 spike protein, fused with a 2A sequence, into the MRV S1 gene segment. For the generation of recombinant MRV expressing the NV protein, we inserted the NV VP1 gene within the MRV S gene segment. The recombinant viruses were analyzed in vitro and in vivo, providing valuable insights for the further development of MRV vectors.

Academic Significance and Societal Importance of the Research Achievements

哺乳類レオウイルス(MRV)は病原性が極めて低く、経鼻、経口投与により粘膜免疫を誘導できることから優れた粘膜ワクチンベクター候補と考えられる。本研究ではヒトノロウイルスおよび新型コロナウイルスのワクチン開発を目的として、各種ウイルス抗原を発現する組換えMRVの作製を行った。in vivoにおける解析結果から、克服すべき課題も見つかり、引き続き、開発研究を進める必要はあるものの、これらの成果は様々な呼吸器・消化器感染症に対するワクチン開発にも応用可能と考えられ、社会的意義も高い。

Report

(3 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • Research Products

    (37 results)

All 2023 2022 2021

All Journal Article (20 results) (of which Int'l Joint Research: 9 results,  Peer Reviewed: 20 results,  Open Access: 9 results) Presentation (15 results) (of which Int'l Joint Research: 4 results,  Invited: 1 results) Book (2 results)

  • [Journal Article] Characterization of Sialic Acid-Independent Simian Rotavirus Mutants in Viral Infection and Pathogenesis2023

    • Author(s)
      Yamasaki Moeko、Kanai Yuta、Wakamura Yoshiki、Kotaki Tomohiro、Minami Shohei、Nouda Ryotaro、Nurdin Jeffery A.、Kobayashi Takeshi
    • Journal Title

      Journal of Virology

      Volume: 97 Issue: 1

    • DOI

      10.1128/jvi.01397-22

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] N-Glycosylation of Rotavirus NSP4 Protein Affects Viral Replication and Pathogenesis.2023

    • Author(s)
      Nurdin JA, Kotaki T, Kawagishi T, Sato S, Yamasaki M, Nouda R, Minami S, Kanai Y, Kobayashi T.
    • Journal Title

      Journal of Virology

      Volume: 97 Issue: 1

    • DOI

      10.1128/jvi.01861-22

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A reverse genetics system for human rotavirus G2P[4]2022

    • Author(s)
      Hamajima Rina、Lusiany Tina、Minami Shohei、Nouda Ryotaro、Nurdin Jeffery A.、Yamasaki Moeko、Kobayashi Nobumichi、Kanai Yuta、Kobayashi Takeshi
    • Journal Title

      Journal of General Virology

      Volume: 103 Issue: 12 Pages: 001816-001816

    • DOI

      10.1099/jgv.0.001816

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Development of an oncolytic mammalian orthoreovirus expressing the near-infrared fluorescent protein iRFP7202022

    • Author(s)
      Ogawa Katsuhiro、Yamada Kentaro、Etoh Tsuyoshi、Kitagawa Masahiro、Shirasaka Yoshinori、Noguchi Kazuko、Kobayashi Takeshi、Nishizono Akira、Inomata Masafumi
    • Journal Title

      Journal of Virological Methods

      Volume: 308 Pages: 114574-114574

    • DOI

      10.1016/j.jviromet.2022.114574

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Emerging norovirus GII.4 Sydney[P31] causing acute gastroenteritis outbreak in children in Japan, during COVID-19, 20212022

    • Author(s)
      Pham Ngan Thi Kim、Nishimura Shuichi、Shimizu-Onda Yuko、Trinh Quang Duy、Komine-Aizawa Shihoko、Khamrin Pattara、Okitsu Shoko、Sato Shintaro、Kobayashi Takeshi、Maneekarn Niwat、Hayakawa Satoshi、Ushijima Hiroshi
    • Journal Title

      Journal of Infection and Chemotherapy

      Volume: 28 Issue: 9 Pages: 1347-1351

    • DOI

      10.1016/j.jiac.2022.05.015

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The nonstructural p17 protein of a fusogenic bat-borne reovirus regulates viral replication in virus species- and host-specific manners2022

    • Author(s)
      Nouda Ryotaro、Kawagishi Takahiro、Kanai Yuta、Shimojima Masayuki、Saijo Masayuki、Matsuura Yoshiharu、Kobayashi Takeshi
    • Journal Title

      PLOS Pathogens

      Volume: 18 Issue: 6 Pages: e1010553-e1010553

    • DOI

      10.1371/journal.ppat.1010553

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Whole genome sequencing and evolutionary analysis of G8P [8] rotaviruses emerging in Japan2022

    • Author(s)
      Phan Tung、Kobayashi Masaaki、Nagasawa Koo、Hatazawa Riona、Thi Kim Pham Ngan、Miyashita Hideaki、Komoto Satoshi、Tajima Takeshi、Baba Tuneyoshi、Okitsu Shoko、Khamrin Pattara、Maneekarn Niwat、Kimura Hirokazu、Kobayashi Takeshi、Hayakawa Satoshi、Ushijima Hiroshi
    • Journal Title

      VirusDisease

      Volume: 33 Issue: 2 Pages: 215-218

    • DOI

      10.1007/s13337-022-00765-z

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Whole genome sequence of an uncommon G9P[4] species A rotavirus containing DS-1-like (genotype 2) genes in Japan2022

    • Author(s)
      Phan Tung、Hatazawa Riona、Komoto Satoshi、Nishimura Shuichi、Khamrin Pattara、Pham Ngan Thi Kim、Okitsu Shoko、Kobayashi Takashi、Maneekarn Niwat、Hayakawa Satoshi、Ushijima Hiroshi
    • Journal Title

      Archives of Virology

      Volume: 167 Issue: 7 Pages: 1603-1606

    • DOI

      10.1007/s00705-022-05462-2

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] An increasing trend of human sapovirus infection in Japan, 2009 to 2019: An emerging public health concern2022

    • Author(s)
      Hoque S. A., Nishimura K, Thongprachum A. , Khamrin P. ,Ngan Thi Kim Pham, Islam M. T. , Khandoker n. , Okitsu S, Onda-Shimizu Y , Dey S. K. ,Maneekarn N. , Kobayashi T, Hayakawa S, Ushijima H.
    • Journal Title

      Journal of Infection and Public Health

      Volume: 15 Issue: 3 Pages: 315-320

    • DOI

      10.1016/j.jiph.2022.01.019

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] SARS-CoV-2 infection triggers paracrine senescence and leads to a sustained senescence-associated inflammatory response2022

    • Author(s)
      Tsuji Shunya、Minami Shohei、Hashimoto Rina、Konishi Yusuke、Suzuki Tatsuya、Kondo Tamae、Sasai Miwa、Torii Shiho、Ono Chikako、Shichinohe Shintaro、Sato Shintaro、et al.
    • Journal Title

      Nature Aging

      Volume: 2 Issue: 2 Pages: 115-124

    • DOI

      10.1038/s43587-022-00170-7

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Ultrasensitive detection of SARS-CoV-2 nucleocapsid protein using large gold nanoparticle-enhanced surface plasmon resonance2022

    • Author(s)
      Yano T, Kajisa T, Ono M, Miyasaka Y, Hasegawa Y, Saito A, Otsuka K, Sakane A, Sasaki T, Yasutomo K, Hamajima R, Kanai Y, Kobayashi T, Matsuura Y, Itonaga M, Yasui T.
    • Journal Title

      Scientific Reports

      Volume: 12 Issue: 1 Pages: 1060-1060

    • DOI

      10.1038/s41598-022-05036-x

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Species A rotavirus reverse genetics: Achievements and prospects2021

    • Author(s)
      Kobayashi T, Patton J.T., Desselberger U.
    • Journal Title

      Virus Research

      Volume: 306 Pages: 198583-198583

    • DOI

      10.1016/j.virusres.2021.198583

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Development of an entirely plasmid-based reverse genetics system for 12-segmented double-stranded RNA viruses2021

    • Author(s)
      Nouda R, Minami S, Kanai Y, Kawagishi T, Nurdin JA, Yamasaki M, Kuwata R, Shimoda H, Maeda K, Kobayash T.
    • Journal Title

      Proceedings of the National Academy of Sciences

      Volume: 118 Issue: 42

    • DOI

      10.1073/pnas.2105334118

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Monoreassortant Rotaviruses of Multiple G Types Are Differentially Neutralized by Sera From Infants Vaccinated With ROTARIX and RotaTeq2021

    • Author(s)
      J. R. Diller, M. H. Carter, Kanai Y, S. V. Sanchez, Kobayashi T, K. M. Ogdena.
    • Journal Title

      The Journal of Infectious Diseases

      Volume: - Issue: 10 Pages: 1720-1729

    • DOI

      10.1093/infdis/jiab479

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] The Detection of Rotavirus Antigenemia by Immunochromatographic Kits: a Case Series.2021

    • Author(s)
      Ushijima H, Hikita T, Kobayashi M, Pham NTK, Onda-Shimizu Y, Kawagishi T, Okitsu S, Kanai Y, Kobayashi T, Phan T, Hoque SA, Takanashi S, Komoto S, Kumthip K, Taniguchi K, Maneekarn N, Hayakawa S, Khamrin P.
    • Journal Title

      Clinical Laboratory

      Volume: 67 Issue: 10/2021 Pages: 2275-2282

    • DOI

      10.7754/clin.lab.2021.210125

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] FAST Proteins: Development and Use of Reverse Genetics Systems for Reoviridae Viruses2021

    • Author(s)
      Kanai Y, Kobayashi T.
    • Journal Title

      Annual Review of Virology

      Volume: 8 Issue: 1 Pages: 515-536

    • DOI

      10.1146/annurev-virology-091919-070225

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Epidemiology and genetic diversity of group A rotavirus in pediatric patients with acute gastroenteritis in Thailand, 2018-20192021

    • Author(s)
      Nutthawadee J, Kattareeya K, Arpaporn Y, Kanai Y, Okitsu S, Kobayashi T, Nuthapong U, Ushijima H, Niwat M, Pattara K.
    • Journal Title

      Infection, Genetics and Evolution

      Volume: 95 Pages: 104898-104898

    • DOI

      10.1016/j.meegid.2021.104898

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] DsRNA Sequencing for RNA Virus Surveillance Using Human Clinical Samples2021

    • Author(s)
      Izum T, Morioka Y, Urayama S, Motooka D, Tamura T, Kawagishi T, Kanai Y, Kobayashi T, Ono C, Morinaga A, Tomiyama T, Iseda N, Kosai Y, Inokuchi S, Nakamura S, Tanaka T, Moriishi K, Kariwa H, Yoshizumi T, Mori M, Matsuura Y, Fukuhara T.
    • Journal Title

      Viruses

      Volume: 13 Issue: 7 Pages: 1310-1310

    • DOI

      10.3390/v13071310

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Rotavirus reverse genetics systems: Development and application2021

    • Author(s)
      Kanai Y, Kobayashi T.
    • Journal Title

      Virus Research

      Volume: 295 Pages: 198296-198296

    • DOI

      10.1016/j.virusres.2021.198296

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Combining machine learning and nanopore construction creates an artificial intelligence nanopore for coronavirus detection2021

    • Author(s)
      Taniguchi M, Minami S, Ono C, Hamajima R, Morimura A, Hamaguchi S, Akeda Y, Kanai Y, Kobayashi T, Kamitani W, Terada Y, Suzuki K, Hatori N, Yamagishi Y, Washizu N, Takei H, Sakamoto O, Naono N, Tatematsu K, Washio T, Matsuura Y, Tomono K.
    • Journal Title

      Nature Communications

      Volume: 12 Issue: 1 Pages: 3726-3726

    • DOI

      10.1038/s41467-021-24001-2

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Whole Genome Characterization of HAstV5-HAstV8-HAstV1 Recombinant Strains of ORF1a-ORF1b-ORF2 Regions2022

    • Author(s)
      Pattara Khamrin, Kattareeya Kumthip, Shintaro Sato, Shoko Okitsu, Takeshi Kobayashi, Satoshi Hayakawa, Hiroshi Ushijima, Niwat Maneekarn
    • Organizer
      第68回日本ウイルス学会学術集会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Recent advances in rotavirus reverse genetics research2022

    • Author(s)
      小林剛
    • Organizer
      第68回日本ウイルス学会学術集会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] ロタウイルス感染に関与する宿主因子Tumor Associated Calcium Signal Transducer 2の機能解析2022

    • Author(s)
      山崎萌子、金井祐太、浜島りな、小瀧将裕、南昌平、納田遼太郎、Jeffery A. Nurdin、小林剛
    • Organizer
      第68回日本ウイルス学会学術集会
    • Related Report
      2022 Annual Research Report
  • [Presentation] ロタウイルスNSP2タンパク質の機能解析2022

    • Author(s)
      小瀧 将裕、金井 祐太、南 昌平、納田 遼太郎、Jeffery A. Nurdin、山﨑 萌子、小林 剛
    • Organizer
      第68回日本ウイルス学会学術集会
    • Related Report
      2022 Annual Research Report
  • [Presentation] マウス順化サルロタウイルスの作出2022

    • Author(s)
      金井 祐太、小瀧 将裕、南 昌平、納田 遼太郎、山﨑 萌子、小林 剛
    • Organizer
      第68回日本ウイルス学会学術集会
    • Related Report
      2022 Annual Research Report
  • [Presentation] ヒトロタウイルスHN126株におけるリバースジェネティクス系の確立2022

    • Author(s)
      浜島 りな、Tina Lusiany、南 昌平、納田 遼太郎、Jeffery A. Nurdin、山﨑 萌子、小林 宣道、金井 祐太、小林 剛
    • Organizer
      第68回日本ウイルス学会学術集会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Single amino acid substitution in VP7 promotes the pathogenicity of simian rotavirus in mice2022

    • Author(s)
      Yuta Kanai, Eriko Hirai, Tomohiro Kotaki and Takeshi Kobayashi
    • Organizer
      14th International dsRNA Virus Symposium
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] N-glycosylation of rotavirus NSP4 protein affects viral replication and pathogenesis2022

    • Author(s)
      Tomohiro Kotaki, Jeffery A. Nurdin, Takahiro Kawagishi, Shintaro Sato, Moeko Yamasaki, Ryotaro Nouda, Shohei Minami, Yuta Kanai, Takeshi Kobayashi
    • Organizer
      14th International dsRNA Virus Symposium
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Analysis of the role of rotavirus NSP4 protein in viral replication and pathogenicity2022

    • Author(s)
      Tomohiro Kotaki, Nurdin Jeffery A., Kawagishi Takahiro, Sato Shintaro, Yamasaki Moeko, Nouda Ryotaro, Minami Shohei, Kanai Yuta, Kobayashi Takeshi
    • Organizer
      第20回 あわじ感染と免疫国際フォーラム
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Identification of TACSTD2 as a host factor involved in rotavirus infection2022

    • Author(s)
      Moeko Yamasaki, Yuta Kanai, Rina Hamajima, Tomohiro Kotaki, Shohei Minami, Ryotaro Nouda, Takeshi Kobayashi.
    • Organizer
      第20回 あわじ感染と免疫国際フォーラム
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] A genome-wide CRISPR-Cas9 screening approach to identify host factors for rotavirus infection CRISPR-Cas9法によるロタウイルス感染に関与する宿主因子のゲノムワイドスクリーニング2021

    • Author(s)
      山﨑 萌子、浜島 りな、金井 祐太、小瀧 将裕、南 昌平、納田 遼太郎、Nurdin Jeffery、小林 剛
    • Organizer
      第68回ウイルス学会学術集会
    • Related Report
      2021 Research-status Report
  • [Presentation] Altered infectivity of rotaviruses in mice treated with antibiotics 抗生物質を投与したマウスにおけるロタウイルスの増殖能2021

    • Author(s)
      金井 祐太、Jeffery Nurdin、南 昌平、納田 遼太郎、山崎 萌子、小林 剛
    • Organizer
      第68回ウイルス学会学術集会
    • Related Report
      2021 Research-status Report
  • [Presentation] Development of an entirely plasmid-based reverse genetics system for 12-segmented double-stranded RNA virus.2021

    • Author(s)
      Ryotaro Nouda, Shohei Minami, Yuta Kanai, Takahiro Kawagishi, Jeffery A. Nurdin, Moeko Yamasaki, Ryusei Kuwata, Hiroshi Shimoda, Ken Maeda, Takeshi Kobayashi.
    • Organizer
      第68回ウイルス学会学術集会
    • Related Report
      2021 Research-status Report
  • [Presentation] Determining the role of rotavirus NSP4 N-glycosylation sites using reverse genetics approach2021

    • Author(s)
      Jeffery A. Nurdin, Yuta Kanai, Tomohiro Kotaki, Takahiro Kawagishi, Shohei Minami, Ryotaro Nouda, Moeko Yamasaki, Takeshi Kobayashi.
    • Organizer
      第68回ウイルス学会学術集会
    • Related Report
      2021 Research-status Report
  • [Presentation] Analysis of intestinal epithelial cells differentiated from human induced pluripotent stem cells as a more suitable tool for the study of SARS-CoV-22021

    • Author(s)
      Shohei Minami, Naomi Matsumoto, Ryotaro Nouda, Jeffery Nurdin, Moeko Yamasaki, Tomohiro Kotaki, Yuta Kanai, Shintaro Sato, Takeshi Kobayashi.
    • Organizer
      第68回ウイルス学会学術集会
    • Related Report
      2021 Research-status Report
  • [Book] 医学のあゆみ280巻9号 ウイルスを創る,ウイルスを視る2021

    • Author(s)
      金井祐太、納田遼太郎、小林 剛
    • Publisher
      医歯薬出版株式会社
    • Related Report
      2021 Research-status Report
  • [Book] 創薬研究者がこれだけは知っておきたい最新のウイルス学2021

    • Author(s)
      金井祐太、納田遼太郎、山﨑萌子、小林 剛
    • Publisher
      技術情報協会
    • ISBN
      9784861048555
    • Related Report
      2021 Research-status Report

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Published: 2021-07-13   Modified: 2024-01-30  

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