IMMUNITY AGAINST PASTEURELLA HAEMOLYTICA LEUKOTOXIN

• Main Authors: HODGSON, ADRIAN LESLIE MARK, PRIDEAUX, CHRISTOPHER THOMAS
• Format: Patent
• Language: English; French
• Published: 29.06.2010
• Subjects: BEER; BIOCHEMISTRY; CHEMISTRY; COMPOSITIONS THEREOF; CULTURE MEDIA; ENZYMOLOGY; FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIREDCHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERSFROM A RACEMIC MIXTURE; HUMAN NECESSITIES; HYGIENE; MEDICAL OR VETERINARY SCIENCE; METALLURGY; MICROBIOLOGY; MICROORGANISMS OR ENZYMES; MUTATION OR GENETIC ENGINEERING; ORGANIC CHEMISTRY; PEPTIDES; PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES; PROPAGATING, PRESERVING OR MAINTAINING MICROORGANISMS; SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS ORMEDICINAL PREPARATIONS; SPIRITS; VINEGAR; WINE

Bovine respiratory disease (BRD) complex, shipping fever, or pneumomic pasteurellosis, is a multifactorial disease whereby a combination of viral infection, adverse environment and poor immune status may combine to predispose animals to bacterial infections. The exotoxin, or leukotoxin (Lkt), may contribute to pathogenesis by impairing the primary lung defenses and subsequent immune responses or by causing inflammations as a result of leukocyte lysis. The present invention provides a modified microorganism which produces an Lkt toxin, wherein said Lkt toxin is partially or fully inactivated. In a further embodiment of the present invention, there is provided a modified microorganism wherein an Lkt toxin operon including an Lkt 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 Lkt toxin has reduced toxic activity. Surprisingly, the Lkt 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 Lkt toxin. A microorganism which naturally produces an Lkt toxin may be engineered to produce an inactive Lkt 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 Lkt toxin precursor or produces an inactivated post-translational activator of the Lkt toxin precursor. The post-translational activator may be a product of the Lkt C gene.