Unlocking the promise of DNA vaccines

基于核酸的疫苗是一种极有希望对抗流行病的工具。它们便宜、安全且对新出现的病原体反应迅速。该应用程序的合作伙伴公司Touchlight Genetics拥有一个易于扩展的GMP准备，完全合成的DNA平台。局限性在于DNA疫苗迄今为止在人体临床试验中表现不佳。有许多变量可能限制DNA疫苗的效力，迫切需要进行系统的基础研究，以确定这些限制因素并制定克服这些因素的方法，以便开发临床有效的DNA疫苗。该项目将重点开发一种DNA编码的流感疫苗。这既有商业价值——2013年季节性流感疫苗的销售额约为31亿美元，也有相当大的社会价值，因为流感是全球大流行的主要风险。特雷戈宁实验室还拥有完善的流感感染模型，可用于测试开发的任何疫苗的功效。该项目的假设是，DNA疫苗的免疫原性可以大大增强，从而更好地转化为临床产品。该学生将与Touchlight Genetics密切合作，生成具有优化免疫原性的合成DNA流感候选疫苗。在之前与Touchlight Genetics的合作中，我们已经证明，他们的线性DNA平台与质粒DNA 3相当，改变给药途径会改变诱导的免疫反应类型，并且诱导肺部常驻T细胞提高对病毒感染的保护。项目目标为：第一年：利用Touchlight的技术平台改变DNA疫苗的体内表达和免疫原性。第二年：设计和测试更广泛和覆盖范围的新型流感DNA疫苗。第三年：研究DNA免疫如何使免疫系统对其他疫苗平台做出更好的反应。

Nucleic acid based vaccines are an extremely promising tool to combat pandemics 1. They are cheap, safe and rapidly responsive to novel emerging pathogens. The partner company for this application, Touchlight Genetics, has a GMP ready, completely synthetic DNA platform that is easily scalable. The limitation is that DNA vaccines have underperformed in human clinical trials to date. There are a large number of variables that may limit the efficacy of DNA vaccines and there is an urgent need to perform systematic underpinning research to identify these limiting factors and develop approaches to overcome them in order to develop clinically effective DNA vaccines. The project will focus on developing a DNA encoded influenza vaccine. This has both commercial value - the sales of seasonal influenza vaccine were approximately $3.1 billion in 2013, and also considerable societal value in the development of vaccines that could prevent pandemic influenza, with flu being the major risk of global pandemics. The Tregoning lab also has well established models of influenza infection 2, that can be used to test the efficacy of any vaccine developed.The hypothesis of the project is that the immunogenicity of DNA vaccines can be dramatically enhanced, leading to better translation into a clinical product.The student will work closely with Touchlight Genetics to generate a synthetic DNA influenza vaccine candidate with optimised immunogenicity. In previous work with Touchlight Genetics, we have shown that their linear DNA platform is comparable to plasmid DNA 3, that altering the route of administration alters the type of immune response induced 4 and that the induction of lung resident T cells improves protection against viral infection 5.The objectives of the project are:Year 1: Use Touchlight's technology platforms to alter the expression and immunogenicity of DNA vaccines in vivo.Year 2: Design and test novel influenza DNA vaccines with increased breadth and coverage.Year 3: Investigate how DNA immunisation can prime the immune system to respond better to other vaccine platforms.