The mechanism of broadly reactive anti-influenza virus antibody responses

Research Project

Project/Area Number	18K06647
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Review Section	Basic Section 47030:Pharmaceutical hygiene and biochemistry-related
Research Institution	Institute of Physical and Chemical Research
Principal Investigator	Miyauchi Kosuke 国立研究開発法人理化学研究所, 生命医科学研究センター, 副チームリーダー (50619856)
Project Period (FY)	2018-04-01 – 2021-03-31
Project Status	Completed (Fiscal Year 2020)
Budget Amount *help	¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000) Fiscal Year 2020: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000) Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000) Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Keywords	ウイルス中和抗体 / インフルエンザウイルス / 濾胞性ヘルパーT細胞 / 抗インフルエンザウイルス抗体 / 広域中和抗体 / 抗ウイルス抗体 / ワクチン / 中和抗体 / ヘルパーT細胞
Outline of Final Research Achievements	Here, we investigated virus-specific antibody responses against the influenza virus infection to elucidate the production mechanism of broadly neutralizing antibodies, which will give us new insight for the development of a universal vaccine. To analyze the immune response induced in the lung by influenza virus infection, we performed transcriptome analysis of lung cells isolated from influenza virus infected mice. In addition, to analyze the difference in virus antigen-specific B cell responses between the infection with live viruses and the vaccination with inactivated viruses, we isolated virus-specific B cells and analyzed their IgG genes. Based on results of these experiments, we revealed that the activation of virus-specific follicular helper T cells in the lung draining lymph nodes induced by infection and the exposure of viral antigens to lung immune system play important roles in the induction of broadly neutralizing antibody responses.
Academic Significance and Societal Importance of the Research Achievements	本研究においてインフルエンザウイルス感染時における広域中和抗体の産生メカニズムの一端が解明できたことで、新興インフルエンザウイルス感染症に対抗するためのユニバーサルワクチンの開発に向けて有用な基礎データを提供できた。これによって、安全性の高い不活化ワクチンを使用しながら、濾胞性ヘルパーT細胞を活性化することで、広域中和抗体を誘導するワクチン投与法の検討を進める方針が確認出来たことは、今後の抗ウイルスワクチン研究において大きな意義をもつと考えられる。