IMMUNITY AGAINST ACTINOBACILLUS PLEUROPNEUMONIAE'S RTX TOXINS APX

摘要

The present invention provides a modified microorganism which produces an RTX toxin, wherein said RTX toxin is partially or fully inactivated. In a further embodiment of the present invention, there is provided a modified microorganism wherein an RTX toxin gene including an RTX structural gene and/or a post-translational activator of the organism is partially or fully inactivated. The present applicants have found that a precursor of an RTX toxin has reduced toxic activity. Surprisingly, the RTX toxin precursor is capable of inducing an immune response in an animal that offers cross protection against heterologous challenge with a microorganism which produces the RTX toxin. A microorganism which naturally produces an RTX toxin may be engineered to produce an inactive RTX toxin precursor by eliminating the post-translational activator of the precursor product. Accordingly, in a preferred embodiment the microorganism is unable to produce a post-translational activator of the RTX toxin precursor or produces an inactivated post-translational activator of the RTX toxin precursor. The post-translational activator may be a product of an RTX C gene. In a further aspect the present invention provides a recombinant plasmid vector for expression of heterologous proteins in Actinobacillus or related organisms. In a preferred embodiment the recombinant plasmid vector is derived from a naturally occurring plasmid in Actinobacillus pleuropneumoniae. The recombinant plasmid may include a DNA sequence which encodes an RTX toxin precursor. The recombinant plasmid may include an RTX A gene. Alternatively, the recombinant plasmid may include an RTX C gene or a fragment thereof.