title: The vaccine potential of Bordetella pertussis biofilm-derived membrane proteins.
abstract: Pertussis is an infectious respiratory disease of humans caused by the gram-negative pathogen Bordetella pertussis. The use of acellular pertussis vaccines (aPs) which induce immunity of relative short duration and the emergence of vaccine-adapted strains are thought to have contributed to the recent resurgence of pertussis in industrialized countries despite high vaccination coverage. Current pertussis vaccines consist of antigens derived from planktonic bacterial cultures. However, recent studies have shown that biofilm formation represents an important aspect of B. pertussis infection, and antigens expressed during this stage may therefore be potential targets for vaccination. Here we provide evidence that vaccination of mice with B. pertussis biofilm-derived membrane proteins protects against infection. Subsequent proteomic analysis of the protein content of biofilm and planktonic cultures yielded 11 proteins which were ≥three-fold more abundant in biofilms, of which Bordetella intermediate protein A (BipA) was the most abundant, surface-exposed protein. As proof of concept, mice were vaccinated with recombinantly produced BipA. Immunization significantly reduced colonization of the lungs and antibodies to BipA were found to efficiently opsonize bacteria. Finally, we confirmed that bipA is expressed during respiratory tract infection of mice, and that anti-BipA antibodies are present in the serum of convalescent whooping cough patients. Together, these data suggest that biofilm proteins and in particular BipA may be of interest for inclusion into future pertussis vaccines.
authors.affiliation: Laboratory of Pediatric Infectious Diseases, Department of Pediatrics, Radboud University Medical Center , Nijmegen 6500 HB, The Netherlands ; Laboratory of Medical Immunology, Department of Laboratory Medicine, Radboud University Medical Center , Nijmegen 6500 HB, The Netherlands.
authors.forename: Daan
authors.initials: D
authors.lastname: de Gouw
authors.affiliation: Nijmegen Centre for Mitochondrial Disorders, Department of Laboratory Medicine, Radboud Proteomics Centre, Radboud University Medical Center , Nijmegen 6525 GA, The Netherlands.
authors.forename: Diego O
authors.initials: DO
authors.lastname: Serra
authors.affiliation: Laboratory of Pediatric Infectious Diseases, Department of Pediatrics, Radboud University Medical Center , Nijmegen 6500 HB, The Netherlands ; Laboratory of Medical Immunology, Department of Laboratory Medicine, Radboud University Medical Center , Nijmegen 6500 HB, The Netherlands.
authors.forename: Marien I
authors.initials: MI
authors.lastname: de Jonge
authors.affiliation: Laboratory of Pediatric Infectious Diseases, Department of Pediatrics, Radboud University Medical Center , Nijmegen 6500 HB, The Netherlands ; Laboratory of Medical Immunology, Department of Laboratory Medicine, Radboud University Medical Center , Nijmegen 6500 HB, The Netherlands.
authors.forename: Peter Wm
authors.initials: PW
authors.lastname: Hermans
authors.affiliation: Netherlands Centre for Infectious Disease Control, National Institute for Public Health and the Environment (RIVM) , Bilthoven 3720 BA, The Netherlands.
authors.forename: Hans Jct
authors.initials: HJ
authors.lastname: Wessels
authors.affiliation: Laboratory of Pediatric Infectious Diseases, Department of Pediatrics, Radboud University Medical Center , Nijmegen 6500 HB, The Netherlands ; Laboratory of Medical Immunology, Department of Laboratory Medicine, Radboud University Medical Center , Nijmegen 6500 HB, The Netherlands.
authors.forename: Aldert
authors.initials: A
authors.lastname: Zomer
authors.affiliation: Nijmegen Centre for Mitochondrial Disorders, Department of Laboratory Medicine, Radboud Proteomics Centre, Radboud University Medical Center , Nijmegen 6525 GA, The Netherlands.
authors.forename: Osvaldo M
authors.initials: OM
authors.lastname: Yantorno
authors.affiliation: Laboratory of Pediatric Infectious Diseases, Department of Pediatrics, Radboud University Medical Center , Nijmegen 6500 HB, The Netherlands ; Laboratory of Medical Immunology, Department of Laboratory Medicine, Radboud University Medical Center , Nijmegen 6500 HB, The Netherlands.
authors.forename: Dimitri A
authors.initials: DA
authors.lastname: Diavatopoulos
authors.affiliation: Laboratory of Pediatric Infectious Diseases, Department of Pediatrics, Radboud University Medical Center , Nijmegen 6500 HB, The Netherlands ; Laboratory of Medical Immunology, Department of Laboratory Medicine, Radboud University Medical Center , Nijmegen 6500 HB, The Netherlands ; Facultad de Ciencias Exactas, Centro de Investigación y Desarrollo en Fermentaciones Industriales (CINDEFI), CONICET-CCT-La Plata, Universidad Nacional de La Plata , La Plata B1900 ASH, Argentina.
authors.forename: Frits R
authors.initials: FR
authors.lastname: Mooi
keywords: BipA; Bordetella pertussis; biofilms; proteomics; vaccination