Novel generic vaccine approaches applied for the prevention of hepatitis C and influenza virus infections.

用于预防丙型肝炎和流感病毒感染的新型仿制疫苗方法。

• 批准号: nhmrc : 436729
• 负责人: Prof Hans Netter
• 金额: $ 26.16万
• 依托单位: Monash University
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2007
• 资助国家: 澳大利亚
• 起止时间: 2007-01-01 至 2009-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/novel-generic-vaccine-virus-infections/92314
• 关键词: Novel; generic; vaccine; approaches; applied

For the induction of good immune responses, antigens should be delivered in several copies on a defined particle. The small envelope protein (HBsAg) encoded by the hepatitis B virus (HBV) has the capacity to self-assemble with host derived lipids into VLPs. HBsAg VLPs are the sole component of one of the most successful vaccines, and clinical trials have shown that they are a successful delivery system for foreign epitopes or protein domains. Hepatitis C virus (HCV) and Influenza viruses are major human pathogens. HCV has infected 200 million people worldwide, and there is no effective vaccine available. Influenza continues to affect thousands of people each year causing epidemics with severe morbidity and considerable mortality. Current influenza vaccines are mostly inactivated formulations and they exhibit poor immunogenicity in immunological naive persons such as children and in the elderly. The influenza vaccines are not optimal for stimulation of cell-mediated immunity. We propose to use particulate antigens as a delivery platform for influenza and HCV-specific epitopes with the focus to develop approaches to target various HCV and influenza strains, including H5N1 bird influenza. We have successfully produced modified VLPs containing HCV-specific sequences, which are able to induce anti-HCV antibodies with neutralising capacity. We hypothesise that the design of VLPs with an appropriate set of HCV-specific antigens will enhance the neutralising capacity of anti-HCV sera and this may overcome strain specificity. This application will exploit a prototype delivery system to induce antibody and also cellular responses against a variety of HCV- and influenza specific target sequences (epitopes). The outcome of this study will be a prototype multivalent vaccine to a range of HCV- and influenza-specific epitopes. As a delivery system this will be ideal for vaccination against agents that are highly variable.

为了诱导良好的免疫应答，抗原应在限定的颗粒上以几个拷贝递送。由B肝炎病毒（HBV）编码的小包膜蛋白（HBsAg）具有与宿主来源的脂质自组装成VLP的能力。HBsAg VLP是最成功的疫苗之一的唯一组分，临床试验表明它们是外源表位或蛋白质结构域的成功递送系统。丙型肝炎病毒（HCV）和流感病毒是人类的主要病原体。HCV在全球范围内感染了2亿人，目前还没有有效的疫苗。流感每年继续影响成千上万的人，引起具有严重发病率和相当高死亡率的流行病。目前的流感疫苗大部分是灭活制剂，并且它们在免疫学幼稚的人（例如儿童和老年人）中表现出差的免疫原性。流感疫苗对于刺激细胞介导的免疫不是最佳的。我们建议使用颗粒抗原作为流感和HCV特异性表位的递送平台，重点是开发针对各种HCV和流感毒株（包括H5N1禽流感）的方法。我们已经成功地生产了修饰的VLP含有HCV特异性序列，这是能够诱导抗HCV抗体的中和能力。我们假设，设计的VLP与一组适当的HCV特异性抗原将提高抗HCV血清的中和能力，这可能会克服菌株的特异性。本申请将利用原型递送系统来诱导针对各种HCV和流感特异性靶序列（表位）的抗体和细胞应答。这项研究的结果将是一个原型多价疫苗的一系列丙型肝炎病毒和流感病毒的特异性表位。作为一种递送系统，这对于针对高度可变的试剂的疫苗接种将是理想的。