title: Immunoproteomic Profiling of Bordetella pertussis Outer Membrane Vesicle Vaccine Reveals Broad and Balanced Humoral Immunogenicity.
abstract: The current resurgence of whooping cough is alarming, and improved pertussis vaccines are thought to offer a solution. Outer membrane vesicle vaccines (omvPV) are potential vaccine candidates, but omvPV-induced humoral responses have not yet been characterized in detail. The purpose of this study was to determine the antigen composition of omvPV and to elucidate the immunogenicity of the individual antigens. Quantitative proteome analysis revealed the complex composition of omvPV. The omvPV immunogenicity profile in mice was compared to those of classic whole cell vaccine (wPV), acellular vaccine (aPV), and pertussis infection. Pertussis-specific antibody levels, antibody isotypes, IgG subclasses, and antigen specificity were determined after vaccination or infection by using a combination of multiplex immunoassays, two-dimensional immunoblotting, and mass spectrometry. The vaccines and infection raised strong antibody responses, but large quantitative and qualitative differences were measured. The highest antibody levels were obtained by omvPV. All IgG subclasses (IgG1/IgG2a/IgG2b/IgG3) were elicited by omvPV and in a lower magnitude by wPV, but not by aPV (IgG1) or infection (IgG2a/b). The majority of omvPV-induced antibodies were directed against Vag8, BrkA, and LPS. The broad and balanced humoral response makes omvPV a promising pertussis vaccine candidate.
authors.affiliation: †Intravacc, Bilthoven 3720 AL, The Netherlands.|‡Division of Drug Delivery Technology, Leiden Academic Centre for Drug Research, Leiden 2300 RA, The Netherlands.
authors.forename: René H M
authors.initials: RH
authors.lastname: Raeven
authors.affiliation: †Intravacc, Bilthoven 3720 AL, The Netherlands.
authors.forename: Larissa
authors.initials: L
authors.lastname: van der Maas
authors.affiliation: †Intravacc, Bilthoven 3720 AL, The Netherlands.
authors.forename: Wichard
authors.initials: W
authors.lastname: Tilstra
authors.affiliation: †Intravacc, Bilthoven 3720 AL, The Netherlands.
authors.forename: Joost P
authors.initials: JP
authors.lastname: Uittenbogaard
authors.affiliation: †Intravacc, Bilthoven 3720 AL, The Netherlands.
authors.forename: Tim H E
authors.initials: TH
authors.lastname: Bindels
authors.affiliation: §Centre for Infectious Disease Control, National Institute for Public Health and the Environment (RIVM), Bilthoven 3720 BA, The Netherlands.
authors.forename: Betsy
authors.initials: B
authors.lastname: Kuipers
authors.affiliation: †Intravacc, Bilthoven 3720 AL, The Netherlands.
authors.forename: Arno
authors.initials: A
authors.lastname: van der Ark
authors.affiliation: ∥Centre for Health Protection (GZB), National Institute for Public Health and the Environment (RIVM), Bilthoven 3720 BA, The Netherlands.
authors.forename: Jeroen L A
authors.initials: JL
authors.lastname: Pennings
authors.affiliation: †Intravacc, Bilthoven 3720 AL, The Netherlands.
authors.forename: Elly
authors.initials: E
authors.lastname: van Riet
authors.affiliation: ‡Division of Drug Delivery Technology, Leiden Academic Centre for Drug Research, Leiden 2300 RA, The Netherlands.
authors.forename: Wim
authors.initials: W
authors.lastname: Jiskoot
authors.affiliation: †Intravacc, Bilthoven 3720 AL, The Netherlands.|‡Division of Drug Delivery Technology, Leiden Academic Centre for Drug Research, Leiden 2300 RA, The Netherlands.
authors.forename: Gideon F A
authors.initials: GF
authors.lastname: Kersten
authors.affiliation: †Intravacc, Bilthoven 3720 AL, The Netherlands.
authors.forename: Bernard
authors.initials: B
authors.lastname: Metz
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis / Q000276:immunology*; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology / Q000378:metabolism*; D001428:Bacterial Vaccines / Q000276:immunology*; D001886:Bordetella pertussis / Q000276:immunology*; D002853:Chromatography, Liquid; D015180:Electrophoresis, Gel, Two-Dimensional; D051379:Mice; D020543:Proteome; D053719:Tandem Mass Spectrometry; D014917:Whooping Cough / Q000517:prevention & control
chemical_list: D000907:Antibodies, Bacterial; D001425:Bacterial Outer Membrane Proteins; D001428:Bacterial Vaccines; D020543:Proteome
keywords: 2D-electrophoresis; Bordetella pertussis; Western blot; antibody; humoral; outer membrane vesicle; proteomics; subclass; vaccine