Using the Information inherent in Immune Responses to Design Vaccines

利用免疫反应中固有的信息来设计疫苗

• 批准号: nhmrc : 454640
• 负责人: Dr Weiguang Zeng
• 金额: $ 35.11万
• 依托单位: The University of Melbourne
• 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/using-information-inherent-design-vaccines/94805
• 关键词: Using; Information; inherent; Immune; Responses

The parts of viruses, bacteria and of cancer cells that are recognised by the immune system are called epitopes. Epitopes are generated from these agents by dendritic cells which are found in many parts of the body where they act as sentinels on the look out for dangerous organisms. Epitopes are very small pieces of the proteins against which immune responses are mounted and can be readily synthesised in the laboratory. If we were to design vaccines that are made of epitopes such that the immune response is focussed to those exact regions of infectious agents it could lead to an immune response that eliminates the agent. The problem is, however, that we usually do not know which part of the virus, bacterium or cancer cell is recognised as an epitope. So the identification of epitopes is a limitation to the design of epitope-based vaccines. Anyone who has encountered a virus, bacterium or tumour cell and who has raised an immune response will have developed antibodies and immune cells able to recognise the right parts of the infectious agent or cancer cell. These antibodies and immune cells now contain information about the epitopes. We will use antibodies and blood cells obtained from people immune to the disease to extract epitopes from a panel of protein fragments that represent the agent against which we wish to make vaccines. These newly discovered epitopes will then be incorporated into totally synthetic vaccines. These vaccines will also incorporate a simple lipid molecule which specifically targets and activates the dendritic cell that is key for the induction of potent immune responses. All of the technologies we propose are in place and we have proof of principle that the approach leads to the successful design of vaccines that are effective against infectious diseases and cancers.

病毒、细菌和癌细胞中被免疫系统识别的部分称为表位。表位是由树突状细胞从这些物质产生的，树突状细胞存在于身体的许多部位，它们充当寻找危险生物体的哨兵。表位是免疫反应所针对的蛋白质的非常小的片段，并且可以在实验室中轻松合成。如果我们要设计由表位组成的疫苗，使免疫反应集中于感染因子的确切区域，则可能会产生消除感染因子的免疫反应。然而问题是，我们通常不知道病毒、细菌或癌细胞的哪一部分被识别为表位。因此，表位的识别是基于表位的疫苗设计的限制。任何遇到病毒、细菌或肿瘤细胞并产生免疫反应的人都会产生能够识别感染原或癌细胞的正确部分的抗体和免疫细胞。这些抗体和免疫细胞现在包含有关表位的信息。我们将使用从对该疾病免疫的人身上获得的抗体和血细胞，从一组蛋白质片段中提取表位，这些表位代表我们希望制造疫苗的试剂。这些新发现的表位将被纳入全合成疫苗中。这些疫苗还将包含一种简单的脂质分子，该分子专门针对并激活树突状细胞，而树突状细胞是诱导有效免疫反应的关键。我们提出的所有技术都已到位，并且我们有原理证明，证明该方法可以成功设计出有效对抗传染病和癌症的疫苗。