Fundamental research to expand indications for dyslipidemia vaccine

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K16429
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 54040:Metabolism and endocrinology-related
• Research Institution: Kumamoto University
• Principal Investigator: Fukami Hirotaka 熊本大学, 大学院生命科学研究部(医), 特任助教 (00908006)
• Project Period (FY): 2022-04-01 – 2024-03-31
• Keywords: ANGPTL3 / ペプチドワクチン / 家族性高コレステロール血症 / 動脈硬化性疾患 / 治療ワクチン

Outline of Final Research Achievements

The current treatment options for atherosclerotic diseases caused by dyslipidemia are inadequate. In a previous study, the applicant confirmed that a vaccine targeting ANGPTL3 significantly improved the lipid profile of a mouse model of obesity. Substantial progress has been made in optimizing both B-cell and T-cell epitopes for practical applications. The current vaccine consists of a 10-amino-acid sequence common to both humans and mice. However, shortened and modified epitopes have been demonstrated to be equally effective. A similar efficacy was observed in diabetic and familial hypercholesterolemia mouse models. Furthermore, the T-cell epitope retained its effectiveness even when the vaccine carrier was replaced with an alternative, indicating that the vaccine is being successfully improved for practical use. These advancements highlight the potential of this vaccine to address the growing need for effective treatment of dyslipidemia and its associated atherosclerotic diseases.

Free Research Field

脂質異常症

Academic Significance and Societal Importance of the Research Achievements

本研究の目的は、脂質異常症およびその関連疾患に対するANGPTL3抑制ワクチンの安全性と有効性を動物実験で確認し、臨床応用の可能性を探ることである。ANGPTL3は血管新生や脂質制御に関与しており、現在ではヒト化抗ANGPTL3モノクローナル抗体が日本や欧米で家族性高コレステロール血症の治療薬として承認されている。しかしながら、抗体薬等のバイオ医薬品は薬価が高く、患者や社会に対する経済的負担を増大させるため、費用対効果に優れたANGPTL3ワクチンの開発が重要である。また、本ワクチンは、既存薬が何らかの理由で使用できない患者に対するセカンドライン薬としても有用である。