Development of broadly neutralizing antibodies against mammarenaviruses

• Project/Area Number: 19K06401
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 42020:Veterinary medical science-related
• Research Institution: Kyoto University
• Principal Investigator: MURAMOTO Yukiko 京都大学, ウイルス・再生医科学研究所, 助教 (70436567)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: アレナウイルス

Outline of Research at the Start

アレナウイルスにはヒトに重篤な出血熱を引き起こすウイルスが多く存在する。中でもラッサウイルスには西アフリカを中心に毎年30万人程度が感染し、5千から1万人が死亡しており、その被害が大きい。さらに散発する出血熱の流行からも新規のアレナウイルスの発見が続いている。今のところ、アレナウイルスに特異的な抗ウイルス薬がないことから、様々なアレナウイルスに対して効果のある抗ウイルス薬の開発が急務である。そこで本研究では、全てのアレナウイルス感染症の治療に利用可能なモノクローナル抗体を、免疫したマウスのリンパ球から作出する。

Outline of Final Research Achievements

Several mammarenaviruses such as Lassa, Junin, Machupo, and Sabia viruses cause hemorrhagic fever in humans. Currently, there are no efficient treatments against mammarenavirus diseases. The goal of the study is to develop neutralizing antibodies that can be available for the treatment of several mammarenavirus infections. To this end, various immunization methods and screening methods for antibody-producing hybridomas were performed. Finally, we obtained several monoclonal antibodies which recognize glycoproteins of several mammarenaviruses.

Academic Significance and Societal Importance of the Research Achievements

抗体医薬品は、一つの抗体が一つの抗原を認識する特異性を利用した、副作用の少ない効果的な治療法として、がん、免疫炎症性疾患、感染症、その他の分野で利用されている。しかし、アレナウイルス感染症の治療法としては未だ実用化されていない。本研究では、複数のアレナウイルス種の表面糖蛋白質を認識するモノクローナル抗体を作出した。広域抗アレナウイルス抗体の作出に適した方法を見出すことができたと言える。

Research Products

• [Journal Article] CP100356 Hydrochloride, a P-Glycoprotein Inhibitor, Inhibits Lassa Virus Entry: Implication of a Candidate Pan-Mammarenavirus Entry Inhibitor (2021)
  • Author(s): Takenaga T, Zhang Z, Muramoto Y, Fehling SK, Hirabayashi A, Takamatsu Y, Kajikawa J, Miyamoto S, Nakano M, Urata S, Groseth A, Strecker T, Noda T.
  • Journal Title: Viruses Volume: 13 Issue: 9 Pages: 1763-1763
  • DOI: 10.3390/v13091763
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Resistance of SARS-CoV-2 variants to neutralization by antibodies induced in convalescent patients with COVID-19 (2021)
  • Author(s): Kaku Y, Kuwata T, Zahid HM, Hashiguchi T, Noda T, Kuramoto N, Biswas S, Matsumoto K, Shimizu M, Kawanami Y, Shimura K, Onishi C, Muramoto Y, Suzuki T, Sasaki J, Nagasaki Y, Minami R, Motozono C, Toyoda M, Takahashi H, Kishi H, Fujii K, Tatsuke T, Ikeda T, Maeda Y, Ueno T, Koyanagi Y, Iwagoe H, Matsushita S.
  • Journal Title: Cell Reports Volume: 36 Issue: 2 Pages: 109385-109385
  • DOI: 10.1016/j.celrep.2021.109385
  • Peer Reviewed / Open Access
• [Journal Article] Modeling SARS-CoV-2 infection and its individual differences with ACE2-expressing human iPS cells (2021)
  • Author(s): Sano Emi、Deguchi Sayaka、Sakamoto Ayaka、Mimura Natsumi、Hirabayashi Ai、Muramoto Yukiko、Noda Takeshi、Yamamoto Takuya、Takayama Kazuo
  • Journal Title: iScience Volume: 24 Issue: 5 Pages: 102428-102428
  • DOI: 10.1016/j.isci.2021.102428
  • NAID: 120007032353
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Amplification-free RNA detection with CRISPR?Cas13 (2021)
  • Author(s): Shinoda Hajime、Taguchi Yuya、Nakagawa Ryoya、Makino Asami、Okazaki Sae、Nakano Masahiro、Muramoto Yukiko、Takahashi Chiharu、Takahashi Ikuko、Ando Jun、Noda Takeshi、Nureki Osamu、Nishimasu Hiroshi、Watanabe Rikiya
  • Journal Title: Communications Biology Volume: 4 Issue: 1 Pages: 476-476
  • DOI: 10.1038/s42003-021-02001-8
  • Peer Reviewed / Open Access
• [Journal Article] Protective Face Mask Filter Capable of Inactivating SARS-CoV-2, and Methicillin-Resistant Staphylococcus aureus and Staphylococcus epidermidis (2021)
  • Author(s): Marti M, Tunon-Molina A, Aachmann FL, Muramoto Y, Noda T, Takayama K, Serrano-Aroca A
  • Journal Title: Polymers Volume: 13 Issue: 2 Pages: 207-207
  • DOI: 10.3390/polym13020207
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Microtubule-dependent transport of arenavirus matrix protein demonstrated using live-cell imaging microscopy. (2019)
  • Author(s): Takamatsu Y, Kajikawa J, Muramoto Y, Nakano M, Noda T.
  • Journal Title: Microscopy (Oxf) Volume: 68 Pages: 450-456
  • DOI: 10.1093/jmicro/dfz034
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Generation of a purely clonal defective interfering influenza virus. (2019)
  • Author(s): Yamagata Y, Muramoto Y, Miyamoto S, Shindo K, Nakano M, Noda T.
  • Journal Title: Microbiol Immunol. Volume: 63 Issue: 5 Pages: 164-171
  • DOI: 10.1111/1348-0421.12681
  • NAID: 40021927501
  • Peer Reviewed / Open Access