title: Protective efficacy afforded by live Pasteurella multocida vaccines in chickens is independent of lipopolysaccharide outer core structure.
abstract: Pasteurella multocida is a major animal pathogen that causes a range of diseases including fowl cholera. P. multocida infections result in considerable losses to layer and breeder flocks in poultry industries worldwide. Both killed whole-cell and live-attenuated vaccines are available; these vaccines vary in their protective efficacy, particularly against heterologous strains. Moreover, until recently there was no knowledge of P. multocida LPS genetics and structure to determine precisely how LPS structure affects the protective capacity of these vaccines. In this study we show that defined lipopolysaccharide (LPS) mutants presented as killed whole-cell vaccines elicited solid protective immunity only against P. multocida challenge strains expressing highly similar or identical LPS structures. This finding indicates that vaccination of commercial flocks with P. multocida killed cell formulations will not protect against strains producing an LPS structure different to that produced by strains included in the vaccine formulation. Conversely, protective immunity conferred by vaccination with live P. multocida strains was found to be largely independent of LPS structure. Birds vaccinated with a range of live mutants belonging to the L1 and L3 LPS genotypes, each expressing a specific truncated LPS structure, were protected against challenge with the parent strain. Moreover, birds vaccinated with any of the five LPS mutants belonging to the L1 LPS genotype were also protected against challenge with an unrelated strain and two of the five groups vaccinated with live LPS mutants belonging to the L3 genotype were protected against challenge with an unrelated strain. In summary, vaccination with live P. multocida aroA mutants producing full-length L1 or L3 LPS or vaccination with live strains producing shortened L1 LPS elicited strong protective immunity against both homologous and heterologous challenge.
authors.affiliation: Infection and Immunity Program, Monash Biomedicine Discovery Institute and Department of Microbiology, Monash University, Melbourne 3800, VIC, Australia. Electronic address: marina.harper@monash.edu.
authors.forename: Marina
authors.initials: M
authors.lastname: Harper
authors.affiliation: Infection and Immunity Program, Monash Biomedicine Discovery Institute and Department of Microbiology, Monash University, Melbourne 3800, VIC, Australia.
authors.forename: Marietta
authors.initials: M
authors.lastname: John
authors.affiliation: Infection and Immunity Program, Monash Biomedicine Discovery Institute and Department of Microbiology, Monash University, Melbourne 3800, VIC, Australia; Poultry CRC, University of New England, Armidale 2351, NSW, Australia.
authors.forename: Mark
authors.initials: M
authors.lastname: Edmunds
authors.affiliation: Infection and Immunity Program, Monash Biomedicine Discovery Institute and Department of Microbiology, Monash University, Melbourne 3800, VIC, Australia.
authors.forename: Amy
authors.initials: A
authors.lastname: Wright
authors.affiliation: CSIRO Livestock Industries, Australian Animal Health Laboratory, Geelong 3220, VIC, Australia.
authors.forename: Mark
authors.initials: M
authors.lastname: Ford
authors.affiliation: Queensland Alliance for Agriculture and Food Innovation, University of Queensland, Brisbane 4072, QLD, Australia.
authors.forename: Conny
authors.initials: C
authors.lastname: Turni
authors.affiliation: Queensland Alliance for Agriculture and Food Innovation, University of Queensland, Brisbane 4072, QLD, Australia.
authors.forename: P J
authors.initials: PJ
authors.lastname: Blackall
authors.affiliation: Vaccine Program, Human Health Therapeutics Portfolio, National Research Council, Ottawa, ON, Canada K1A 0R6.
authors.forename: Andrew
authors.initials: A
authors.lastname: Cox
authors.affiliation: Infection and Immunity Program, Monash Biomedicine Discovery Institute and Department of Microbiology, Monash University, Melbourne 3800, VIC, Australia.
authors.forename: Ben
authors.initials: B
authors.lastname: Adler
authors.affiliation: Infection and Immunity Program, Monash Biomedicine Discovery Institute and Department of Microbiology, Monash University, Melbourne 3800, VIC, Australia.
authors.forename: John D
authors.initials: JD
authors.lastname: Boyce
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D001428:Bacterial Vaccines / Q000276:immunology*; D002645:Chickens; D056738:Cross Protection; D008070:Lipopolysaccharides / Q000737:chemistry* / Q000235:genetics; D050505:Mutant Proteins / Q000737:chemistry / Q000235:genetics; D010326:Pasteurella Infections / Q000517:prevention & control / Q000662:veterinary*; D016979:Pasteurella multocida / Q000235:genetics; D011201:Poultry Diseases / Q000382:microbiology / Q000517:prevention & control*; D014613:Vaccines, Attenuated / Q000276:immunology
chemical_list: D000907:Antibodies, Bacterial; D001428:Bacterial Vaccines; D008070:Lipopolysaccharides; D050505:Mutant Proteins; D014613:Vaccines, Attenuated
keywords: Lipopolysaccharide; Pasteurella multocida; Vaccine