title: Proteomics-identified Bvg-activated autotransporters protect against bordetella pertussis in a mouse model.
abstract: Pertussis is a highly infectious respiratory disease of humans caused by the bacterium Bordetella pertussis. Despite high vaccination coverage, pertussis has re-emerged globally. Causes for the re-emergence of pertussis include limited duration of protection conferred by acellular pertussis vaccines (aP) and pathogen adaptation. Pathogen adaptations involve antigenic divergence with vaccine strains, the emergence of strains which show enhanced in vitro expression of a number of virulence-associated genes and of strains that do not express pertactin, an important aP component. Clearly, the identification of more effective B. pertussis vaccine antigens is of utmost importance. To identify novel antigens, we used proteomics to identify B. pertussis proteins regulated by the master virulence regulatory system BvgAS in vitro. Five candidates proteins were selected and it was confirmed that they were also expressed in the lungs of naïve mice seven days after infection. The five proteins were expressed in recombinant form, adjuvanted with alum and used to immunize mice as stand-alone antigens. Subsequent respiratory challenge showed that immunization with the autotransporters Vag8 and SphB1 significantly reduced bacterial load in the lungs. Whilst these antigens induced strong opsonizing antibody responses, we found that none of the tested alum-adjuvanted vaccines - including a three-component aP - reduced bacterial load in the nasopharynx, suggesting that alternative immunological responses may be required for efficient bacterial clearance from the nasopharynx.
authors.forename: Daan
authors.initials: D
authors.lastname: de Gouw
authors.affiliation: Laboratory of Pediatric Infectious Diseases, Department of Pediatrics, Radboud University Medical Centre, Nijmegen, The Netherlands; Laboratory of Medical Immunology, Department of Laboratory Medicine, Radboud University Medical Centre, Nijmegen, The Netherlands.
authors.forename: Daan de
authors.initials: Dd
authors.lastname: Gouw
authors.forename: Marien I
authors.initials: MI
authors.lastname: de Jonge
authors.affiliation: Laboratory of Pediatric Infectious Diseases, Department of Pediatrics, Radboud University Medical Centre, Nijmegen, The Netherlands; Laboratory of Medical Immunology, Department of Laboratory Medicine, Radboud University Medical Centre, Nijmegen, The Netherlands.
authors.forename: Marien I de
authors.initials: MI
authors.lastname: Jonge
authors.affiliation: Laboratory of Pediatric Infectious Diseases, Department of Pediatrics, Radboud University Medical Centre, Nijmegen, The Netherlands; Laboratory of Medical Immunology, Department of Laboratory Medicine, Radboud University Medical Centre, Nijmegen, The Netherlands.
authors.forename: Peter W M
authors.initials: PW
authors.lastname: Hermans
authors.affiliation: Nijmegen Centre for Mitochondrial Disorders, Department of Laboratory Medicine, Radboud Proteomics Centre, Radboud University Medical Centre, Nijmegen, The Netherlands.
authors.forename: Hans J C T
authors.initials: HJ
authors.lastname: Wessels
authors.affiliation: Laboratory of Pediatric Infectious Diseases, Department of Pediatrics, Radboud University Medical Centre, Nijmegen, The Netherlands; Laboratory of Medical Immunology, Department of Laboratory Medicine, Radboud University Medical Centre, Nijmegen, The Netherlands.
authors.forename: Aldert
authors.initials: A
authors.lastname: Zomer
authors.affiliation: Laboratory of Pediatric Infectious Diseases, Department of Pediatrics, Radboud University Medical Centre, Nijmegen, The Netherlands; Laboratory of Medical Immunology, Department of Laboratory Medicine, Radboud University Medical Centre, Nijmegen, The Netherlands.
authors.forename: Alinda
authors.initials: A
authors.lastname: Berends
authors.affiliation: Public Health England, Centre for Emergency Preparedness and Response, Porton Down, Salisbury, United Kingdom.
authors.forename: Catherine
authors.initials: C
authors.lastname: Pratt
authors.affiliation: Netherlands Centre for Infectious Disease Control, National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands.
authors.forename: Guy A
authors.initials: GA
authors.lastname: Berbers
authors.affiliation: Laboratory of Pediatric Infectious Diseases, Department of Pediatrics, Radboud University Medical Centre, Nijmegen, The Netherlands; Laboratory of Medical Immunology, Department of Laboratory Medicine, Radboud University Medical Centre, Nijmegen, The Netherlands; Netherlands Centre for Infectious Disease Control, National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands.
authors.forename: Frits R
authors.initials: FR
authors.lastname: Mooi
authors.affiliation: Laboratory of Pediatric Infectious Diseases, Department of Pediatrics, Radboud University Medical Centre, Nijmegen, The Netherlands; Laboratory of Medical Immunology, Department of Laboratory Medicine, Radboud University Medical Centre, Nijmegen, The Netherlands.
authors.forename: Dimitri A
authors.initials: DA
authors.lastname: Diavatopoulos
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology* / Q000378:metabolism*; D001426:Bacterial Proteins / Q000276:immunology / Q000378:metabolism; D001886:Bordetella pertussis / Q000276:immunology* / Q000502:physiology; D004195:Disease Models, Animal; D005260:Female; D008168:Lung / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D010567:Pertussis Vaccine / Q000276:immunology / Q000378:metabolism; D040901:Proteomics; D014917:Whooping Cough / Q000276:immunology / Q000517:prevention & control
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D010567:Pertussis Vaccine