Development of the induction method of the long-lived plasma cells for new vaccine strategies

• Project/Area Number: 17K08895
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Immunology
• Research Institution: National Institute of Infectious Diseases
• Principal Investigator: Onodera Taishi 国立感染症研究所, 免疫部, 主任研究官 (90513143)
• Project Period (FY): 2017-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2020: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: ウイルス感染 / 免疫記憶 / ワクチン / 長期生存型抗体産生細胞 / ウイルス感染症 / I型IFNシグナル / Bリンパ球 / インフルエンザ / 抗体 / 免疫学

Outline of Final Research Achievements

In this study, we clarify that the type I IFN signaling is involved in the enhanced formation of long-lived plasma cell which involved in long-lasting maintenance of serum antibody titer after influenza virus infection. By utilizing adopted transfer method and in vivo fate mapping of type I IFN receptor deficient and influenza HA specific BCR transgenic B cells, we reveal that both B cell intrinsic and extrinsic type I IFN signaling are necessary for enhanced formation of long-lived plasma cells. In addition, to elucidate the molecular mechanisms under the type I IFN signaling in B cells, we establish the experimental system of inducible gene expression of target genes in primary B cells in vivo.

Academic Significance and Societal Importance of the Research Achievements

近年猛威を振るっている新型コロナウイルスやインフルエンザウイルス感染症に対して最も有効な手段はワクチンによって免疫記憶を付与することである。この免疫記憶の持続期間を自在にコントロールできれば1回のワクチン接種で生涯免疫が付与できることが実現可能となる。本研究では、抗体価の長期の維持を担っている長期生存型抗体産生細胞の形成に関わる細胞学的、また分子学的なメカニズムを明らかにすることにより免疫をより長期に持続させることが可能なワクチンストラテジーを開発する足掛かりを得ることができた。今後、本研究で得られた知見を発展させることでより有効なワクチンの開発が期待できる。

Research Products

• [Journal Article] Myeloid cell dynamics correlating with clinical outcomes of severe COVID-19 in Japan (2021)
  • Author(s): 2.Takano T, Matsumura T, Adachi Y, Terahara K, Moriyama S, Onodera T, Nishiyama A, Kawana-Tachikawa A, Miki S, Hosoya-Nakayama K, Nakamura-Hoshi M, Seki S, Tachikawa N, Yoshimura Y, Miyata N, Horiuchi H, Sasaki H, Miyazaki K, Kinoshita N, Sudo T, Akiyama Y, Sato R, Suzuki T, Matano T, Takahashi Y
  • Journal Title: International Immunology Volume: 33 Issue: 4 Pages: 241-247
  • DOI: 10.1093/intimm/dxab005
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Association of Human Leukocyte Antigen DRB1*09:01 with severe COVID-19 (2021)
  • Author(s): 3.Anzurez A, Naka I, Miki S, Hosoya-Nakayama K, Isshiki M, Watanabe Y, Nakamura-Hoshi M, Seki S, Matsumura T, Takano T, Onodera T, Tanaka K, Takahashi Y, Suzuki T, Matano T, Ohashi J, Kawana-Tachikawa A.
  • Journal Title: HLA Volume: 18 Issue: 1 Pages: 1-6
  • DOI: 10.1111/tan.14256
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Identification of Two Critical Neutralizing Epitopes in the Receptor Binding Domain of Hepatitis B Virus preS1 (2020)
  • Author(s): Yato Keigo、Onodera Taishi、Matsuda Mami、Moriyama Saya、Fujimoto Akira、Watashi Koichi、Aizaki Hideki、Tanaka Tomohisa、Moriishi Kohji、Nishitsuji Hironori、Shimotohno Kunitada、Tamura Koji、Takahashi Yoshimasa、Wakita Takaji、Muramatsu Masamichi、Kato Takanobu、Suzuki Ryosuke
  • Journal Title: Journal of Virology Volume: 95 Issue: 5
  • DOI: 10.1128/jvi.01680-20
  • Peer Reviewed / Open Access
• [Journal Article] Immune-Focusing Properties of Virus-like Particles Improve Protective IgA Responses (2019)
  • Author(s): Onodera T, Hashi K, Shukla RK, Miki M, Takai-Todaka R, Fujimoto A, Kuraoka M, Miyoshi T, Kobayashi K, Hasegawa H, Ato M, Kelsoe G, Katayama K, Takahashi Y
  • Journal Title: Journal of Immunology Volume: 203(12) Issue: 12 Pages: 3282-3292
  • DOI: 10.4049/jimmunol.1900481
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Antigen Engineering Focuses Immune Responses to a Subdominant but Broadly Protective Viral Epitope (2019)
  • Author(s): Bajic G, Maron MJ, Adachi Y, Onodera T, McCarthy KR, McGee CE, Sempowski GD, Takahashi Y, Kelsoe G, Kuraoka M, Schmidt AG.Influenza
  • Journal Title: Cell Host and Microbe Volume: 25(6) Issue: 6 Pages: 827-835
  • DOI: 10.1016/j.chom.2019.04.003
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Antibodies to a Conserved Influenza Head Interface Epitope Protect by an IgG Subtype-Dependent Mechanism (2019)
  • Author(s): Watanabe A, McCarthy KR, Kuraoka M, Schmidt AG, Adachi Y, Onodera T, Tonouchi K, Caradonna TM, Bajic G, Song S, McGee CE, Sempowski GD, Feng F, Urick P, Kepler TB, Takahashi Y, Harrison SC, Kelsoe G.Influenza
  • Journal Title: Cell Volume: 177(5) Issue: 5 Pages: 1124-1135
  • DOI: 10.1016/j.cell.2019.03.048
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Adaptive B cell responses to influenza virus infection in the lung. (2017)
  • Author(s): Takahashi, Y., Onodera, T., Adachi, Y., Ato, M
  • Journal Title: Viral Immunology Volume: 30 Issue: 6 Pages: 431-437
  • DOI: 10.1089/vim.2017.0025
  • Peer Reviewed
• [Presentation] Virus-like particle structure enhances protective IgA antibody responses against noroviruses (2018)
  • Author(s): Taishi Onodera, Manabu Ato, Yoshimasa Takahashi
  • Organizer: 日本免疫学会