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

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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.