Pilot study: the use of gene expression profiles to predict protective immunity without the need for disease challenge

试点研究：利用基因表达谱预测保护性免疫力，无需进行疾病挑战

• 批准号: G1100148/1
• 负责人: Roland Ashford
• 金额: $ 4.87万
• 依托单位: ANIMAL AND PLANT HEALTH AGENCY
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2012
• 资助国家: 英国
• 起止时间: 2012 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G1100148%2F1
• 关键词: Pilot; study; use; gene; expression

In order to develop new vaccines, or new ways of delivering vaccines, it is necessary to demonstrate that they provide protection from the disease of interest. One of the most frequently employed ways of doing this is by the use of vaccination challenge studies. In such studies laboratory animals are immunized with the vaccine and then exposed to the disease of interest: if the vaccine is effective then the animals are protected from illness (or at least more protected than animals which did not receive the vaccine). In the case of certain diseases, the number of laboratory animals which are used in these kinds of studies can be reduced by measuring the immune response of the animals following vaccination. In such cases, the immune response can be used to predict how well an animal will be protected from disease, without the need to actually expose it to the disease causing organism. However, in the case of tuberculosis, as well as a number of other important diseases, reliable immune response predictors of vaccination success have eluded identification because there is no single immune response (e.g. antibody production) associated with protection from disease. This project aims to assess whether a recently developed technique called ?RNA sequencing? can be used to address this problem. The immune response to tuberculosis is complicated, and involves the combined action of several different types of cells, which are co-ordinated by protein messenger molecules and protein molecules on the surfaces of cells. In turn, these are controlled by genes, which can be either up-regulated or down-regulated. RNA sequencing allows the degree to which these genes are being up or down-regulated to be measured. Hence it is possible to study the combined immune response of an individual following vaccination, rather than studying specific components. The samples which will be analysed in this study come from badgers vaccinated against tuberculosis. Badgers are known to be susceptible to infection with tuberculosis, and can transmit the disease to cattle. As badgers are legally protected in the United Kingdom, vaccinating them against tuberculosis provides a potentially valuable approach to controlling the disease in cattle. This project aims to identify immune responses in badgers following vaccination which predict how well protected they will be from tuberculosis, using RNA sequencing. Identifying such responses has the potential to reduce the number of animals which need to be used in this kind of research.

为了开发新的疫苗或提供疫苗的新疫苗，有必要证明它们可以保护免受感兴趣疾病的保护。这样做的最常使用的方法之一是使用疫苗接种挑战研究。在此类研究中，实验动物用疫苗免疫，然后暴露于感兴趣的疾病：如果疫苗有效，则动物免受疾病的侵害（或至少比未接受疫苗的动物更受保护）。在某些疾病的情况下，可以通过测量疫苗接种后的动物的免疫反应来减少这些研究中使用的实验动物数量。在这种情况下，可以使用免疫反应来预测动物免受疾病的影响，而无需将其实际暴露于引起生物体的疾病。然而，在结核病以及许多其他重要疾病的情况下，可靠的免疫反应预测因素成功地鉴定了鉴定，因为没有与疾病保护相关的单一免疫反应（例如抗体产生）。该项目旨在评估最近开发的技术是否称为RNA测序？可用于解决此问题。对结核病的免疫反应很复杂，涉及几种不同类型的细胞的联合作用，这些作用由细胞表面上的蛋白质信使分子和蛋白质分子协调。反过来，这些由基因控制，这些基因可以被上调或下调。 RNA测序允许将这些基因上调或下调以测量的程度。因此，可以研究疫苗接种后个体的联合免疫反应，而不是研究特定成分。将在这项研究中分析的样品来自疫苗接种结核病。已知badge很容易感染结核病，可以将疾病传播到牛。由于英国在法律上受到法律保护，因此对结核病进行疫苗接种，为控制牛的疾病提供了一种潜在的有价值的方法。该项目旨在确定疫苗接种后badge中的免疫反应，以预测使用RNA测序对结核病的保护程度。确定这种反应有可能减少需要在此类研究中使用的动物数量。