The role of Gas6/Axl signal in the immune response associated with RSV infection

• Project/Area Number: 16H06246
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Single-year Grants
• Research Field: Respiratory organ internal medicine
• Research Institution: National Institute of Infectious Diseases
• Principal Investigator: Shibata Takehiko 国立感染症研究所, 免疫部, 主任研究官 (00739196)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥24,180,000 (Direct Cost: ¥18,600,000、Indirect Cost: ¥5,580,000); Fiscal Year 2018: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000); Fiscal Year 2017: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000); Fiscal Year 2016: ¥11,960,000 (Direct Cost: ¥9,200,000、Indirect Cost: ¥2,760,000)
• Keywords: Axl / RSV / タイプ2免疫 / ワクチン / Gas6 / アレルギー / 感染症 / 免疫学 / ウィルス / アレルギー・ぜんそく

Outline of Final Research Achievements

Respiratory syncytial virus (RSV) vaccine is currently not available. In this study, we examined the induction mechanism of allergic responses after vaccination with RSV and type 2 immune response with RSV infection. First, it was revealed that growth arrest specific 6 produced by formalin fixed RSV induces type 2 immune response (allergic airway inflammation) via its receptor Axl. We also found that Axl inhibitor shift the immune response from type 2 to 1 and can be an adjuvant and also useful for the elimination of RSV.

Academic Significance and Societal Importance of the Research Achievements

本研究の成果は、安全性と有効性を担保した新しいrespiratory syncytial virus (RSV) ワクチン接種方法となる可能性がある。また、Axlシグナル阻害により免疫応答をシフトさせるという新しい概念は、抗ウイルス薬の開発につながる可能性がある。

Research Products

• [Journal Article] A critical role of Gas6/Axl signal in allergic airway responses during RSV vaccine-enhanced disease (2017)
  • Author(s): Shibata Takehiko、Ato Manabu
  • Journal Title: Immunology & Cell Biology Volume: 95 Issue: 10 Pages: 906-915
  • DOI: 10.1038/icb.2017.61
  • Peer Reviewed
• [Presentation] RSV induces suppressive Gas6/Axl signaling in macrophages increasing susceptibility to secondary S. pneumoniae infection. (2018)
  • Author(s): Takehiko Shibata, Toshihiro Ito, Yoshimasa Takahashi, Manabu Ato
  • Organizer: The 47th Annual Meeting of The Japanese Society for Immunology
• [Presentation] RSV-induced Gas6/Axl signal ultimately leads to severer bacterial pneumonia (2017)
  • Author(s): Takehiko Shibata
  • Organizer: the 5th Annual Meeting of the International Cytokine and Interferon Society
  • Int'l Joint Research
• [Presentation] The role of RSV-induced Gas6/Axl signaling in secondary bacterial infection. (2017)
  • Author(s): Takehiko Shibata
  • Organizer: 第46回日本免疫学会学術集会
• [Presentation] Gas6/Axl signal causes the failure of RSV vaccine development in mice. (2016)
  • Author(s): Takehiko Shibata, Manabu Ato
  • Organizer: The 24th International Symposium on Molecular Cell Biology of Macrophages
  • Int'l Joint Research
• [Presentation] Gas6/Axl signal plays critical roles in allergic responses and insufficient protection by formalin-inactivated RSV vaccine in mice (2016)
  • Author(s): Takehiko Shibata, Manabu Ato
  • Organizer: 第45回日本免疫学会学術集会46回日本免疫学会学術集会