Combination antiviral and immune therapies for hepatitis B virus infection.

针对乙型肝炎病毒感染的抗病毒和免疫联合疗法。

• 批准号: nhmrc : 158011
• 负责人: A/Pr Allison Jilbert
• 金额: $ 15.14万
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2001
• 资助国家: 澳大利亚
• 起止时间: 2001-01-01 至 2003-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/combination-antiviral-immune-virus-infection/78398
• 关键词: Combination; antiviral; immune; therapies; hepatitis

Hepatitis B virus (HBV) causes acute and persistent (chronic) infection with varying degrees of liver damage and a strong association with the development of liver cancer. Worldwide ~ 250 million people have persistent HBV infection and while a HBV vaccine is available that protects against infection, current treatments for existing infection are largely ineffective. We wish to study a combination of antiviral drug therapy and vaccination with DNA vaccines, to develop new treatment protocols for persistent hepatitis B virus (HBV) infection. The human HBV is a member of the hepadnavirus family that includes a number of other very similar host-specific viruses. Therapies will be tested in ducks infected with the duck hepatitis B virus (DHBV) as these animals provide the only model system available in Australia for development of HBV therapies. DHBV-infected ducks will be treated with a new and extremely potent antiviral drug Entacavir (ETV; Bristol-Myers Squibb). Drug treatment will be combined with various DNA vaccination protocols, including new strategies that involve DNA vaccine priming and recombinant fowlpoxvirus (rFPV) boosting of immune responses. Inoculation of DNA vaccines and rFPV results in expression of viral proteins that are presented to the immune system and evoke strong immune responses. 'Prime boost' protocols with DNA vaccines and rFPV have shown promise for protection against and treatment of human immunodeficiency virus (AIDS virus) infection. We will assess the effect of treatment by measuring levels of DHBV in liver and blood, clearance of infected cells and serological changes. The ultimate aim is to develop successful therapies that can then be applied to treatment and elimination of HBV infection in humans.

B型肝炎病毒（HBV）引起急性和持续（慢性）感染，伴有不同程度的肝损伤，并与肝癌的发展密切相关。全世界约有2.5亿人患有持续性HBV感染，虽然有HBV疫苗可预防感染，但目前对现有感染的治疗基本无效。我们希望研究抗病毒药物治疗和DNA疫苗接种相结合，以开发新的治疗方案，持续性B型肝炎病毒（HBV）感染。人HBV是嗜肝DNA病毒家族的成员，该家族包括许多其他非常相似的宿主特异性病毒。治疗将在感染鸭B肝炎病毒（DHBV）的鸭中进行测试，因为这些动物提供了澳大利亚唯一可用的HBV治疗开发模型系统。DHBV感染的鸭子将用一种新的非常有效的抗病毒药物恩他卡韦（ETV;百时美施贵宝）治疗。药物治疗将与各种DNA疫苗接种方案相结合，包括涉及DNA疫苗引发和重组鸡痘病毒（rFPV）增强免疫应答的新策略。DNA疫苗和rFPV的接种导致病毒蛋白的表达，所述病毒蛋白被呈递给免疫系统并引起强烈的免疫应答。使用DNA疫苗和rFPV的“初免加强”方案已显示出预防和治疗人类免疫缺陷病毒（AIDS病毒）感染的希望。我们将通过测量肝脏和血液中DHBV的水平、感染细胞的清除率和血清学变化来评估治疗效果。最终目标是开发成功的治疗方法，然后应用于治疗和消除人类HBV感染。