Analysis of the mechanism of influenza severity caused by hyporesponsiveness of humoral immune responses
Project/Area Number |
17K08801
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Experimental pathology
|
Research Institution | Tokyo Metropolitan Institute of Medical Science |
Principal Investigator |
YASUI Fumihiko 公益財団法人東京都医学総合研究所, 疾患制御研究分野, プロジェクトリーダー (40399473)
|
Project Period (FY) |
2017-04-01 – 2021-03-31
|
Project Status |
Completed (Fiscal Year 2020)
|
Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
|
Keywords | 低応答性 / 液性免疫 / 高病原性鳥インフルエンザ / 重症肺炎 / B細胞濾胞 / 高病原性 / 重症化 / ワクチン / 宿主免疫 / 感染症 |
Outline of Final Research Achievements |
To analyze the adaptive immune response to highly pathogenic avian influenza (HPAI) H5N1 virus infection that causes severe pneumonia, we compared the pathogenesis and induction of antigen-specific antibodies in mice and cynomolgus macaques infected with seasonal H1N1 or HPAI H5N1 viruses. In HPAI H5N1 virus-infected animals, the interaction between dendritic cells and CD4+ T cells was more sparse and antibody induction was much weaker than in H1N1-infected animals. It was considered that the severity of HPAI H5N1 virus infection was due to abnormal dendritic cell activation and accumulation, and subsequent failure of T cells to activate B cells and reduce antibody production. In contrast, prophylactic vaccination induced potent antibody production and prevented severe disease caused by HPAI H5N1 virus infection.
|
Academic Significance and Societal Importance of the Research Achievements |
これまで高病原性鳥インフルエンザ(HPAI)H5N1ウイルス感染による重症化機序の解析は、ウイルス因子を中心に行われてきた。今回、ウイルス因子のみならず、宿主免疫応答性の低下もHPAI H5N1ウイルス感染による重症化に関わっている可能性を示すことができた。また、抗体誘導の低応答性は、抗原提示細胞である樹状細胞の活性化及び集積異常であることが判明し、自然免疫から獲得免疫まで影響受けていた。 更に、高度弱毒化ワクシニアウイルスベクターを用いたH5亜型ワクチンを作出し、良好な発症防御効果を確認した。HPAI H5N1ウイルス感染に対する重症化阻止には、予防ワクチンの開発が非常に重要であるを示せた。
|
Report
(5 results)
Research Products
(5 results)
-
-
-
[Presentation] Evaluation of vaccine potential of recombinant vaccinia virus encoding H5 subtype hemagglutinin against H5N1 influenza viruses2018
Author(s)
Fumihiko Yasui, Keisuke Munekata, Tomoko Fujiyuki, Takeshi Kuraishi, Tomoko Honda, Yoshihiro Sakoda, Misako Yoneda, Hiroshi Kida, Shosaku Hattori, Chieko Kai, Michinori Kohara
Organizer
12th Vaccine Congress
Related Report
Int'l Joint Research
-
-