Live attenuated vaccines to prevent against disease caused by A. pleuropneumoniae.

胸膜肺炎放线杆菌（APP）是一种导致猪肺部疾病的细菌，在全世界的养猪业中造成大量死亡、痛苦和经济损失。抗生素和疫苗用于控制由APP引起的疾病。抗生素耐药性已经很普遍，而且还在不断增加，目前的疫苗并不能保护猪免受所有16种（血清型）APP的侵害，而且通常不能阻止细菌在猪之间传播。迫切需要新的疫苗。我们的目标是开发一种由一株（或多株）APP组成的疫苗，这种疫苗不会引起肺部疾病，但可以诱导猪的免疫反应，从而保护它们免受APP感染。这种“减毒活疫苗”（lav）的优点是生产成本低廉，并能预防多种血清型病毒。APP LAV将由单一菌株（或菌株组合）组成，其中包含APP产生的三种主要“Apx”毒素。针对Apx毒素的免疫反应被认为是保护猪免受APP疾病的重要因素。至关重要的是，lav会产生灭活形式的Apx毒素，但每一种都仍然能够诱导免疫反应。此外，我们将对LAV菌株进行遗传改变，以便通过测试确定动物感染的是天然（非LAV） APP菌株还是LAV疫苗中的菌株。APP可以与其他APP交换DNA， LAV菌株（不会引起肺部疾病）转换回原始形式（会引起肺部疾病）的风险很小。因此，最后，我们将进行进一步的遗传改变，以防止APP菌株之间的DNA交换，并将lav还原为其自然的“毒性”形式。有效的抗APP疾病LAV的可用性将导致全球养猪业死亡、痛苦和经济损失的大幅减少。

Actinobacillus pleuropneumoniae (APP) is a bacterium that causes a lung disease in pigs and is responsible for substantial deaths, suffering and economic losses in the worldwide pig industry. Antibiotics and vaccines are used to control disease caused by APP. Antibiotic resistance is already common and increasing, and current vaccines do not protect pigs against all of the 16 types (serovars) of APP, and typically do not prevent the bacterium passing from pig to pig. There is an urgent need for new vaccines. We aim to develop a vaccine that consists of a strain (or strains) of APP that does not cause lung disease but can induce an immune response in pigs such that they are protected against APP infection. Such "live attenuated vaccines" (LAVs) have the advantage of being cheap to produce and protect against many serovars. The APP LAV will consist of a single strain (or combination of strains) such that it contains the three major "Apx" toxins produced by APP. An immune response against the Apx toxins is considered important to protect pigs against APP disease. Crucially, the LAVs will produce inactivated forms of the Apx toxins but each will still be capable of inducing an immune response. In addition, we will make genetic changes in the LAV strains so that tests can determine whether animals have been infected with a natural (non-LAV) APP strain or those in the LAV vaccine. APP can exchange DNA with other APP and there is a very small risk that LAV strains (do not cause lung disease) might be converted back to their original form (can cause lung disease). Finally, therefore, we will make a further genetic change that will prevent the exchange of DNA between APP strains and reversion of LAVs to their natural "virulent" form. The availability of an effective LAV against APP disease will lead to a substantial decrease in deaths, suffering and economic losses in the worldwide pig industry.