The role of<i>B. pertussis</i>vaccine antigen gene variants in pertussis resurgence and possible consequences for vaccine development

Preston, Andrew

doi:10.1080/21645515.2015.1137402

Cited by 11 publications

(8 citation statements)

References 23 publications

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“…B. pertussis is considered a re-emerging pathogen, with pertussis disease resurgent in numerous countries [ 39 ]. This has been associated with a change from the use of first generation, whole cell to second-generation, acellular pertussis vaccines.…”

Section: Discussionmentioning

confidence: 99%

A curated genome-scale metabolic model of Bordetella pertussis metabolism

et al. 2017

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The Gram-negative bacterium Bordetella pertussis is the causative agent of whooping cough, a serious respiratory infection causing hundreds of thousands of deaths annually worldwide. There are effective vaccines, but their production requires growing large quantities of B. pertussis. Unfortunately, B. pertussis has relatively slow growth in culture, with low biomass yields and variable growth characteristics. B. pertussis also requires a relatively expensive growth medium. We present a new, curated flux balance analysis-based model of B. pertussis metabolism. We enhance the model with an experimentally-determined biomass objective function, and we perform extensive manual curation. We test the model’s predictions with a genome-wide screen for essential genes using a transposon-directed insertional sequencing (TraDIS) approach. We test its predictions of growth for different carbon sources in the medium. The model predicts essentiality with an accuracy of 83% and correctly predicts improvements in growth under increased glutamate:fumarate ratios. We provide the model in SBML format, along with gene essentiality predictions.

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Section: Discussionmentioning

confidence: 99%

A curated genome-scale metabolic model of Bordetella pertussis metabolism

et al. 2017

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“…After more than half a century, whooping cough has yet to be eradicated and there are signs for resurgence despite routine childhood immunization [3,6] with high coverage [5]. Some authors have hypothesized that the resurgence is due to short-lived protection from aP compared to wP [6,7]. Nevertheless, the waning of immunity from aP cannot explain all of the resurgence.…”

Section: Introductionmentioning

confidence: 99%

“…For example, in the Netherlands and in Denmark, the incidence of whooping cough began to surge before wP were replaced by aP in the national immunization program [6,8]. Evidence from recent research supports the adaptation of B. pertussis to vaccine-induced immunity through antigen evolution [7,9]. Most notably, some strains of pertussis no longer produce pertactin (PRN) [3][4][5]10], a protein that enables the bacteria to attach to the lining of human's airway [11] and which is one of the components used in 3-component (aP3) and 5-component (aP5) vaccines [3][4][5]10,11].…”

Section: Introductionmentioning

confidence: 99%

Determining Factors for Pertussis Vaccination Policy: A Study in Five EU Countries

et al. 2020

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Pertussis vaccination policy varies across Europe, not only in the type of vaccine—whole cell (wP) vs. acellular (aP1/2/3/5)—but also in the schedule and recommendation for parents. This study aims to investigate the determining factors for the type of vaccine, immunization schedule and maternal immunization recommendation. From March to May 2019, experts in national health agencies and major academic or research institutions from Denmark, France, Poland, Sweden and the UK were invited to a semi-structured interview. Thematic analysis was performed on the transcripts using a codebook formulated by three coders. Inter-coder agreement was assessed. Fifteen expert interviews were conducted. The identified driving factors for pertussis vaccine policy were classified into three domains: scientific factors, sociological factors, and pragmatic factors. The determining factors for the type of vaccine were prescriber’s preference, concern of adverse events following immunization (AEFI), effectiveness, and consideration of other vaccine components in combined vaccines. The determining factors for infant schedule were immunity response and the potential to improve coverage and timeliness. The determining factors for maternal immunization were infant mortality and public acceptability. To conclude, socio-political and pragmatic factors were, besides scientific factors, important in determining the pertussis vaccine type, schedule of childhood immunization and recommendations for parents.

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“…Pertussis is considered resurgent in many parts of the world, despite high levels of vaccination. Possible reasons for this have been well discussed (reviewed in [4 5 6 –7]). Resurgence has emphasized sizeable gaps in the understanding of the mechanisms of B. pertussis pathogenesis and of B. pertussis physiology.…”

Section: Introductionmentioning

confidence: 99%

The evolution of Bordetella pertussis has selected for mutations of acr that lead to sensitivity to hydrophobic molecules and fatty acids

MacArthur

Belcher

King

et al. 2019

Emerging Microbes & Infections

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Whooping cough, or pertussis, is resurgent in numerous countries worldwide. This has renewed interest in Bordetella pertussis biology and vaccinology. The in vitro growth of B. pertussis has been a source of difficulty, both for the study of the organism and the production of pertussis vaccines. It is inhibited by fatty acids and other hydrophobic molecules. The AcrAB efflux system is present in many different bacteria and in combination with an outer membrane factor exports acriflavine and other small hydrophobic molecules from the cell. Here, we identify that the speciation of B. pertussis has selected for an Acr system that is naturally mutated and displays reduced activity compared to B. bronchiseptica , in which the system appears intact. Replacement of the B. pertussis locus with that of B. bronchiseptica conferred higher levels of resistance to growth inhibition by acriflavine and fatty acids. In addition, we identified that the transcription of the locus is repressed by a LysR-type transcriptional regulator. Palmitate de-represses the expression of the acr locus, dependent on the LysR regulator, strongly suggesting that it is a transcriptional repressor that is regulated by palmitate. It is intriguing that the speciation of B. pertussis has selected for a reduction in activity of the Acr efflux system that typically is regarded as protective to bacteria.

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The role ofB. pertussisvaccine antigen gene variants in pertussis resurgence and possible consequences for vaccine development

Cited by 11 publications

References 23 publications

A curated genome-scale metabolic model of Bordetella pertussis metabolism

A curated genome-scale metabolic model of Bordetella pertussis metabolism

Determining Factors for Pertussis Vaccination Policy: A Study in Five EU Countries

The evolution of Bordetella pertussis has selected for mutations of acr that lead to sensitivity to hydrophobic molecules and fatty acids

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