title: Genomic analysis of isolates from the United Kingdom 2012 pertussis outbreak reveals that vaccine antigen genes are unusually fast evolving.
abstract: A major outbreak of whooping cough, or pertussis, occurred in 2012 in the United Kingdom (UK), with nearly 10 000 laboratory-confirmed cases and 14 infant deaths attributed to pertussis. A worldwide resurgence of pertussis has been linked to switch to the use of acellular pertussis vaccines and the evolution of Bordetella pertussis away from vaccine-mediated immunity. We have conducted genomic analyses of multiple strains from the UK outbreak. We show that the UK outbreak was polyclonal in nature, caused by multiple distinct but closely related strains. Importantly, we demonstrate that acellular vaccine antigen-encoding genes are evolving at higher rates than other surface protein-encoding genes. This was true even prior to the introduction of pertussis vaccines but has become more pronounced since the introduction of the current acellular vaccines. The fast evolution of vaccine antigen-encoding genes has serious consequences for the ability of current vaccines to continue to control pertussis.
authors.affiliation: Department of Biology and Biochemistry, University of Bath Public Health England, Respiratory and Vaccine Preventable Bacteria Reference Unit, London.
authors.forename: Katie L
authors.initials: KL
authors.lastname: Sealey
authors.affiliation: Wellcome Trust Sanger Institute, Hinxton.
authors.forename: Simon R
authors.initials: SR
authors.lastname: Harris
authors.affiliation: Public Health England, Respiratory and Vaccine Preventable Bacteria Reference Unit, London.
authors.forename: Norman K
authors.initials: NK
authors.lastname: Fry
authors.affiliation: Department of Biology and Biochemistry, University of Bath.
authors.forename: Laurence D
authors.initials: LD
authors.lastname: Hurst
authors.affiliation: Public Health England, Porton Down, Salisbury, United Kingdom.
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Gorringe
authors.affiliation: Wellcome Trust Sanger Institute, Hinxton.
authors.forename: Julian
authors.initials: J
authors.lastname: Parkhill
authors.affiliation: Department of Biology and Biochemistry, University of Bath.
authors.forename: Andrew
authors.initials: A
authors.lastname: Preston
mesh_terms: D000942:Antigens, Bacterial / Q000235:genetics*; D001428:Bacterial Vaccines / Q000276:immunology*; D001886:Bordetella pertussis / Q000235:genetics* / Q000276:immunology; D004196:Disease Outbreaks; D019143:Evolution, Molecular; D016680:Genome, Bacterial; D006801:Humans; D010802:Phylogeny; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA; D006113:United Kingdom / Q000453:epidemiology; D014917:Whooping Cough / Q000453:epidemiology / Q000382:microbiology* / Q000517:prevention & control
chemical_list: D000942:Antigens, Bacterial; D001428:Bacterial Vaccines
keywords: evolution; genomics; pertussis; vaccine