VACCINE: G. mellonella as a model to predict vaccine efficacy of bacterial pig pathogens

胸膜肺炎放线杆菌(APP)是一种引起猪肺部疾病的细菌。在严重的情况下(急性疾病)，动物可能在24小时内死亡，或者它们可能会患上与呼吸问题和发育缓慢有关的长期感染(慢性病)。APP对全球养猪业造成的巨大痛苦和经济损失负有责任。疫苗被用来控制疾病，但最广泛使用的(被杀死的细菌)并不能防止APP在猪之间传播，也不能保护猪免受已知的15种细菌中的一种的影响。因此，迫切需要新的疫苗。正在开发的最有希望的疫苗类型之一是使用生活在猪体内的APP菌株，不会导致疾病，并防止感染。这些所谓的减毒活疫苗(LAV)可以预防15种APP中的许多种，并防止APP从一头猪传染给另一头猪。它们由APP毒株组成，这些毒株的DNA发生突变，防止它们导致临床疾病。找到合适的LAV并测试它们是否有效涉及到使用猪和\或老鼠--猪是APP唯一已知的自然宿主。没有简单的实验室测试可以预测APP突变是否会导致猪疾病并产生良好的LAV。在前期工作中，首先，我们用APP菌株感染了蜡蛾(一种昆虫)的幼虫，这些菌株能或不能引起猪的疾病。在蜡蛾身上发现的结果与在猪身上发现的类似。其次，我们发现，给予已知有希望的LAV作为疫苗可以保护蜡蛾免受APP感染。综上所述，我们的结果表明，蜡蛾可以作为一个模型来预测APP突变是否会导致疾病，并将在猪身上产生良好的LAV。在这个项目中，我们将弄清楚影响模型的蜡蛾和细菌因素是什么，以及它是如何工作的。成功将导致APP迫切需要的新疫苗开发的时间和成本的减少，在世界各地APP研究中大幅取代猪和老鼠的使用，并更好地了解昆虫的免疫系统以及它们如何抵御细菌的感染。

Actinobacillus pleuropneumoniae (APP) is a bacterium that causes lung disease in pigs. In severe cases (acute disease) animals can die within 24 hours or alternatively they can get a long lasting infection (chronic disease) which is associated with breathing problems and slow development. APP is responsible for both substantial suffering and economic losses in the worldwide pig industry. Vaccines are given to control disease but the most widely used (killed bacteria) do not prevent APP from being passed from one pig to another or protect pigs against one of the 15 types of the bacterium known. Thus there is an urgent need for new vaccines. One of the most promising vaccine types in development is the use APP strains that live in the pig, do not cause disease, and protect against infection. These so called live attenuated vaccines (LAVs) protect against many of the 15 types of APP and prevent APP from being passed from one pig to another. They consist of APP strains that have mutations in their DNA that prevent them from causing clinical disease. Finding suitable LAVs and testing whether they work involves the use of pigs - the only known natural host for APP - and\or mice. There is no simple laboratory test that can predict whether an APP mutant causes disease in pigs and will make a good LAV. In preliminary work we have, firstly, infected larvae of the wax moth (an insect) with strains of APP that do or do not cause disease in pigs. Similar results were found in the wax moth to those in pigs. Secondly, we found that giving known promising LAVs as a vaccine protects the wax moth from APP infection. Together, our results suggest that the wax moth can be used as a model to predict whether an APP mutant causes disease and will make a good LAV in pigs. In this project, we will work out what are the wax moth and bacterial factors that affect the model and how it works. Success will lead to a decrease in the time to, and costs involved in, the development of urgently needed new vaccines for APP, a substantial replacement in the use of pigs and mice in APP research throughout the world, and a greater understanding of the immune system of insects and how they fight off infection from bacteria.