Immune response to intranasal tau vaccine in the brain and the use of nanoparticles as vectors

2023 Fiscal Year Final Research Report

• Project/Area Number: 21H02807
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 51030:Pathophysiologic neuroscience-related
• Research Institution: Kyoto University
• Principal Investigator: Inoue Haruhisa 京都大学, iPS細胞研究所, 教授 (70332327)
• Co-Investigator(Kenkyū-buntansha): 佐原 成彦 国立研究開発法人量子科学技術研究開発機構, 量子医科学研究所 脳機能イメージング研究部, 上席研究員 (40261185) ; 渡辺 亮 京都大学, 医学研究科, 特定准教授 (60506765)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: タウワクチン / 脳内免疫応答 / ナノ粒子 / シングルセル解析

Outline of Final Research Achievements

Brain single cell analysis was performed on tauopathic mice injected with viral vaccine vectors. In addition, nanoparticles were prepared for use in intranasal tau vaccine vectors, and they were administered to mice to examine their transduction efficiency, etc. The microglial fraction was further classified and analyzed by a cell classification method based on gene expression profiles from single-cell analysis data, and it was found that the number of microglia showing elevated expression of anti-inflammatory genes was increased in tauopathic mice treated with the viral vaccine vector. The results of this analysis showed that tauopathic mice treated with the viral vaccine vector exhibited increased microglia expression. As a result, they identified cell fractions that are altered by viral vaccine vector administration and it was concluded that viral vaccines may suppress neuroinflammation.

Free Research Field

病態神経科学

Academic Significance and Societal Importance of the Research Achievements

タウオパチーモデルマウスにおいて、病態抑制効果を示した点鼻ワクチンの例はこれまでなく、そのワクチンの病態抑制効果の解明は学術的独自性を有する。さらに、グリア炎症は、病態悪化に寄与する面もあるとされるが、本例ではワクチン投与初期に一過性のグリア炎症の上昇が見られ、通常の神経変性疾患に伴う慢性的なグリア炎症と、治療効果を有するグリア炎症それぞれの脳内免疫応答性の解明は学術的意義があると考えられる。超高齢社会における認知症の予防は重要な課題であり、高齢者数が増えていくことが想定されている状況下での、予防ワクチンの研究は創造性を有すると考えられる。