Development of vaccine therapy for achieving HBsAg loss in chronic hepatitis B

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K07983
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: Ehime University
• Principal Investigator: YOSHIDA Osamu 愛媛大学, 医学部附属病院, 講師 (70746809)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: HBV / 治療ワクチン

Outline of Final Research Achievements

HBV therapeutic vaccine containing HBsAg and HBcAg was administrated to HBV transgenic mouse, model of HBV asymptomatic carrier. Total 5 doses of the therapeutic vaccine were injected through nose every 2 weeks. After 5 doses injection, all the HBV-Tg (n=5) obtained anti-HBs (404.8±172.3 mIU/mL). 40% (n=2/5) of HBV-Tg lost HBsAg after the 5 doses injection, the mean HBsAg was reduced to 2.2±3.9% compared with the baseline. HBsAg/HBcAg specific CTLs were detected in the spleen after the therapeutic vaccine injection. HBxAg was added to improve the immunogenicity of the therapeutic vaccine, however HBxAg did not amplify the anti-HBs induction and HBsAg reduction in HBVTg mouse.

Free Research Field

肝臓学

Academic Significance and Societal Importance of the Research Achievements

HBV治療にはIFNと核酸アナログが用いられるが、副作用、長期服用、治療対象者の選別などの問題点がある。HBV排除にはHBV特異的なHBV応答が重要であり、治療ワクチンは新たな治療法となりうる。HBs抗原とHBc抗原を含む治療ワクチンの効果を確認したが、更なる治療効果（HBs抗原の低下、消失）が望まれる。本研究プロジェクトでは、マウスの経鼻投与法とHBV特異的な免疫応答（液性、細胞性）の解析方法を確立した。さらに、HBx抗原添加による治療増強効果を期待したが、治療効果の増強は確認できなかった。今後、抗原量、投与法などのプロトコールを改良し、治療ワクチンの改良を行う。