Innovative viral vaccine strategy promoting broad-reactive neutralizing antibodies.

2021 Fiscal Year Final Research Report

• Project/Area Number: 19H03491
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 49070:Immunology-related
• Research Institution: Tokyo University of Science
• Principal Investigator: Masato Kubo 東京理科大学, 研究推進機構生命医科学研究所, 教授 (40277281)
• Co-Investigator(Kenkyū-buntansha): 宮内 浩典 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): 2019-04-01 – 2022-03-31
• Keywords: インフルエンザ / ワクチン / 広域中和抗体 / B細胞 / T細胞

Outline of Final Research Achievements

Influenza viruses are a major public health problem, and vaccines offer the effective protective strategy against influenza virus infection. The goal of this proposal is to develop a vaccine with efficacy against newly emerged variant viruses. It has been reported that inactivated vaccines is narrow compared to potential breadth of virus infection. In contrast, live attenuated vaccines (LAV) have the advantage of inducing broadly reactive neutralizing antibodies. Analysis of this mechanism showed that the broadly reactive neutralizing antibodies induced by LAV could recognize a common epitope present in different H1N1 viral strains, and B cells were already set up in pre-existing B cell repertoires. Normally, this common epitope is hidden in native form, so that sufficient amounts of broadly reactive antibodies are not produced, but when the common epitope is exposed during the viral replication process, these B cells are amplified by TFH-derived IL-4 in the secondary lymphoid tissues.

Free Research Field

免疫学

Academic Significance and Societal Importance of the Research Achievements

本研究の成果により、生ワクチンが持つ広域中和抗体を効率よく産生できる優位性が示された。この成果は現行、流行が起こっている新型コロナウイルスでも活用することが期待でき、社会的貢献度は非常に高い。しかしながら、弱毒生ワクチンの問題点は、副反応にあることは容易に予想できる。そのため、ウイルスが持つ生物特性を利用した新しいワクチン戦略の構築が、これから現れる変異体に対するワクチン戦略として必要となる。本研究は、そのヒントになる情報を提供できたと考えている。