Immunoproteomic Profiling of <i>Bordetella pertussis</i> Outer Membrane Vesicle Vaccine Reveals Broad and Balanced Humoral Immunogenicity

Raeven, René H. M.; Maas, Larissa van der; Tilstra, Wichard; Uittenbogaard, Joost P.; Bindels, Tim H E; Kuipers, Betsy; Ark, Arno van der; Pennings, Jeroen L. A.; Riet, Elly van; Jiskoot, Wim; Kersten, Gideon; Metz, Bernard

doi:10.1021/acs.jproteome.5b00258

Cited by 70 publications

(117 citation statements)

References 69 publications

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“…Both omvPV and wPV were diluted in PBS to a final concentration of 4 μg total protein per immunization dose (300 μl). Vaccine characterization included particle size, protein composition, and LPS and DNA content7. For the challenge culture, stock suspension of B. pertussis strain B1917 was diluted in Verweij medium (BBio, Bilthoven, The Netherlands) to a final concentration of 5 × 10 6 colony-forming units (cfu)/ml.…”

Section: Methodsmentioning

confidence: 99%

“…Antigen specificity of B. pertussis -specific serum IgG antibody responses were determined by SDS-PAGE and subsequent Western blotting as described before7.…”

Section: Methodsmentioning

confidence: 99%

“…The current view on immunity to Bordetella pertussis ( B. pertussis ) is that T-helper 1 and 17 (Th1/Th17) responses34 and specific antibody responses are preferred for protection. wPV induce a predominant Th1/Th17 response456 and a broad systemic antibody repertoire7, but are associated with mild adverse effects89. The suspected correlation between wPV and serious acute neurological illness in children1011 has finally led to the call for safer pertussis vaccines.…”

mentioning

confidence: 99%

“…Recent findings for aPV suggest waning immunity in children12 and impaired prevention of transmission in baboons13. It is thought that aPV induce suboptimal antibody7 and T-cell responses14. These drawbacks call again for improved pertussis vaccines.…”

mentioning

confidence: 99%

“…The protection in mice induced by omvPV is comparable to that of aPV, based on lung colonization data after B. pertussis challenge1516. Nevertheless, the omvPV elicits a broader humoral immunity and T-cell response compared to aPV717. To match the high short-term efficacy and good safety profile of current aPVs, a more comprehensive insight into omvPV-induced responses is required to unravel the type of immunity and assist in future vaccine registration.…”

mentioning

confidence: 99%

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Bordetella pertussis outer membrane vesicle vaccine confers equal efficacy in mice with milder inflammatory responses compared to a whole-cell vaccine

Raeven

Brummelman

Pennings

et al. 2016

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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.

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Section: Methodsmentioning

confidence: 99%

“…Antigen specificity of B. pertussis -specific serum IgG antibody responses were determined by SDS-PAGE and subsequent Western blotting as described before7.…”

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Bordetella pertussis outer membrane vesicle vaccine confers equal efficacy in mice with milder inflammatory responses compared to a whole-cell vaccine

Raeven

Brummelman

Pennings

et al. 2016

Sci Rep

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PlasmoSEP: Predicting surface-exposed proteins on the malaria parasite using semisupervised self-training and expert-annotated data

et al. 2016

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Accurate and comprehensive identification of surface-exposed proteins (SEPs) in parasites is a key step in developing novel subunit vaccines. However, the reliability of MS-based high-throughput methods for proteome-wide mapping of SEPs continues to be limited due to high rates of false positives (i.e., proteins mistakenly identified as surface exposed) as well as false negatives (i.e., SEPs not detected due to low expression or other technical limitations). We propose a framework called PlasmoSEP for the reliable identification of SEPs using a novel semisupervised learning algorithm that combines SEPs identified by high-throughput experiments and expert annotation of high-throughput data to augment labeled data for training a predictive model. Our experiments using high-throughput data from the Plasmodium falciparum surface-exposed proteome provide several novel high-confidence predictions of SEPs in P. falciparum and also confirm expert annotations for several others. Furthermore, PlasmoSEP predicts that 25 of 37 experimentally identified SEPs in Plasmodium yoelii salivary gland sporozoites are likely to be SEPs. Finally, PlasmoSEP predicts several novel SEPs in P. yoelii and Plasmodium vivax malaria parasites that can be validated for further vaccine studies. Our computational framework can be easily adapted to improve the interpretation of data from high-throughput studies.

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Proteomic Adaptation of Australian Epidemic Bordetella pertussis

et al. 2018

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Bordetella pertussis causes whooping cough. The predominant strains in Australia changed to single nucleotide polymorphism (SNP) cluster I (pertussis toxin promoter allele ptxP3/pertactin gene allele prn2) from cluster II (non-ptxP3/non-prn2). Cluster I was mostly responsible for the 2008-2012 Australian epidemic and was found to have higher fitness compared to cluster II using an in vivo mouse competition assay, regardless of host's immunization status. This study aimed to identify proteomic differences that explain higher fitness in cluster I using isobaric tags for relative and absolute quantification (iTRAQ), and high-resolution multiple reaction monitoring (MRM-hr). A few key differences in the whole cell and secretome were identified between the cluster I and II strains tested. In the whole cell, nine proteins were upregulated (>1.2 fold change, q < 0.05) and three were downregulated (<0.8 fold change, q < 0.05) in cluster I. One downregulated protein was BP1569, a TLR2 agonist for Th1 immunity. In the secretome, 12 proteins were upregulated and 1 was downregulated which was Bsp22, a type III secretion system (T3SS) protein. Furthermore, there was a trend of downregulation in three T3SS effectors and other virulence factors. Three proteins were upregulated in both whole cell and supernatant: BP0200, molybdate ABC transporter (ModB), and tracheal colonization factor A (TcfA). Important expression differences in lipoprotein, T3SS, and transport proteins between the cluster I and II strains were identified. These differences may affect immune evasion, virulence and metabolism, and play a role in increased fitness of cluster I.

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Immunoproteomic Profiling of Bordetella pertussis Outer Membrane Vesicle Vaccine Reveals Broad and Balanced Humoral Immunogenicity

Cited by 70 publications

References 69 publications

Bordetella pertussis outer membrane vesicle vaccine confers equal efficacy in mice with milder inflammatory responses compared to a whole-cell vaccine

Bordetella pertussis outer membrane vesicle vaccine confers equal efficacy in mice with milder inflammatory responses compared to a whole-cell vaccine

PlasmoSEP: Predicting surface-exposed proteins on the malaria parasite using semisupervised self-training and expert-annotated data

Proteomic Adaptation of Australian Epidemic Bordetella pertussis

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