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，或者他们可能会得到一个长期持续的感染（慢性疾病），这是与呼吸问题和缓慢的发展。APP对全球养猪业造成了巨大的痛苦和经济损失。疫苗是用来控制疾病的，但最广泛使用的（杀死的细菌）并不能阻止APP从一头猪传给另一头猪，也不能保护猪免受15种已知细菌中的一种。因此，迫切需要新的疫苗。正在开发的最有前途的疫苗类型之一是使用生活在猪体内的APP菌株，不会引起疾病，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从一头猪传给另一头猪。它们由APP菌株组成，这些菌株的DNA中存在突变，可以防止它们引起临床疾病。寻找合适的LAV并测试它们是否有效涉及使用猪-APP唯一已知的天然宿主-和/或小鼠。没有简单的实验室测试可以预测APP突变体是否会导致猪的疾病，并将成为一个良好的LAV。在初步工作中，我们首先用APP菌株感染了蜡螟（一种昆虫）的幼虫，这些菌株会或不会引起猪的疾病。在蜡螟中发现了与猪相似的结果。其次，我们发现，给已知有前途的LAV作为疫苗保护蜡螟免受APP感染。总之，我们的研究结果表明，蜡螟可以作为一个模型来预测APP突变体是否会导致疾病，并将使一个很好的LAV在猪。在这个项目中，我们将研究影响模型的蜡螟和细菌因素以及它是如何工作的。成功将导致开发迫切需要的APP新疫苗的时间和成本减少，在世界各地的APP研究中大量替代猪和小鼠的使用，并更好地了解免疫系统昆虫以及它们如何对抗细菌感染。

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.