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

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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.