title: Bordetella pertussis outer membrane vesicle vaccine confers equal efficacy in mice with milder inflammatory responses compared to a whole-cell vaccine.
abstract: The demand for improved pertussis vaccines is urgent due to the resurgence of whooping cough. A deeper understanding of the mode of action of pertussis vaccines is required to achieve this improvement. The vaccine-induced effects of a candidate outer membrane vesicle vaccine (omvPV) and a classical protective but reactogenic whole cell vaccine (wPV) were comprehensively compared in mice. The comparison revealed essential qualitative and quantitative differences with respect to immunogenicity and adverse effects for these vaccines. Both vaccines stimulated a mixed systemic Th1/Th2/Th17 response. Remarkably, omvPV evoked higher IgG levels, lower systemic pro-inflammatory cytokine responses and enhanced splenic gene expression than wPV. The omvPV-induced transcriptome revealed gene signatures of the IFN-signaling pathway, anti-inflammatory signatures that attenuate LPS responses, anti-inflammatory metabolic signatures, and IgG responses. Upon intranasal challenge, both immunized groups were equally efficient in clearing Bordetella pertussis from the lungs. This study importantly shows that immunization with omvPV provides a milder inflammatory responses but with equal protection to bacterial colonization and induction of protective antibody and Th1/Th17 type immune responses compared to wPV. These results emphasize the potential of omvPV as a safe and effective next-generation pertussis vaccine.
authors.affiliation: Institute for Translational Vaccinology (Intravacc), Bilthoven, The Netherlands.|Division of Drug Delivery Technology, Leiden Academic Centre for Drug Research, Leiden, The Netherlands.
authors.forename: René H M
authors.initials: RH
authors.lastname: Raeven
authors.affiliation: Centre for Infectious Disease Control, National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands.
authors.forename: Jolanda
authors.initials: J
authors.lastname: Brummelman
authors.affiliation: Centre for Health Protection (GZB), National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands.
authors.forename: Jeroen L A
authors.initials: JL
authors.lastname: Pennings
authors.affiliation: Institute for Translational Vaccinology (Intravacc), Bilthoven, The Netherlands.
authors.forename: Larissa
authors.initials: L
authors.lastname: van der Maas
authors.affiliation: Institute for Translational Vaccinology (Intravacc), Bilthoven, The Netherlands.
authors.forename: Wichard
authors.initials: W
authors.lastname: Tilstra
authors.affiliation: Centre for Infectious Disease Control, National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands.
authors.forename: Kina
authors.initials: K
authors.lastname: Helm
authors.affiliation: Institute for Translational Vaccinology (Intravacc), Bilthoven, 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, The Netherlands.
authors.forename: Wim
authors.initials: W
authors.lastname: Jiskoot
authors.affiliation: Centre for Infectious Disease Control, National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands.
authors.forename: Cécile A C M
authors.initials: CA
authors.lastname: van Els
authors.affiliation: Centre for Infectious Disease Control, National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands.
authors.forename: Wanda G H
authors.initials: WG
authors.lastname: Han
authors.affiliation: Institute for Translational Vaccinology (Intravacc), Bilthoven, The Netherlands.|Division of Drug Delivery Technology, Leiden Academic Centre for Drug Research, Leiden, The Netherlands.
authors.forename: Gideon F A
authors.initials: GF
authors.lastname: Kersten
authors.affiliation: Institute for Translational Vaccinology (Intravacc), Bilthoven, The Netherlands.
authors.forename: Bernard
authors.initials: B
authors.lastname: Metz
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology*; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology* / Q000494:pharmacology; D001428:Bacterial Vaccines / Q000276:immunology* / Q000494:pharmacology; D001886:Bordetella pertussis / Q000276:immunology*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology*; D007074:Immunoglobulin G / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
chemical_list: D000907:Antibodies, Bacterial; D001425:Bacterial Outer Membrane Proteins; D001428:Bacterial Vaccines; D007074:Immunoglobulin G