Acellular Pertussis Vaccine Components: Today and Tomorrow

Dewan, Kalyan K.; Linz, Bodo; DeRocco, Susan E.; Harvill, Eric T.

doi:10.3390/vaccines8020217

Cited by 33 publications

(33 citation statements)

References 84 publications

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“…These results demonstrate that aP vaccination fails to prevent nasopharyngeal colonization in this experimental system. This approach can measure the differences between wP and aP vaccines in this regard, providing an assay in which to evaluate various proposed new vaccines that might prevent colonization better than current aP vaccines (34,35).…”

Section: Vaccination Effects On Colonizationmentioning

confidence: 99%

Modeling Immune Evasion and Vaccine Limitations by Targeted Nasopharyngeal Bordetella pertussis Inoculation in Mice

Soumana¹,

Linz²,

Dewan³

et al. 2021

Emerg. Infect. Dis.

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Section: Vaccination Effects On Colonizationmentioning

confidence: 99%

Modeling Immune Evasion and Vaccine Limitations by Targeted Nasopharyngeal Bordetella pertussis Inoculation in Mice

Soumana¹,

Linz²,

Dewan³

et al. 2021

Emerg. Infect. Dis.

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“…A whole-cell pertussis vaccine that was introduced in the fifties of the previous century was effective but generated significant side effects. Therefore, it was replaced by subunit-based vaccines, which were shown to be safe and effective in inducing protective immunity [ 1 ]. However, particularly the industrialized countries, where these vaccines are in use, have witnessed a resurgence of pertussis in the past decades [ 2 ].…”

Section: Introductionmentioning

confidence: 99%

Shortening the Lipid A Acyl Chains of Bordetella pertussis Enables Depletion of Lipopolysaccharide Endotoxic Activity

et al. 2020

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Whooping cough, or pertussis, is an acute respiratory infectious disease caused by the Gram-negative bacterium Bordetella pertussis. Whole-cell vaccines, which were introduced in the fifties of the previous century and proved to be effective, showed considerable reactogenicity and were replaced by subunit vaccines around the turn of the century. However, there is a considerable increase in the number of cases in industrialized countries. A possible strategy to improve vaccine-induced protection is the development of new, non-toxic, whole-cell pertussis vaccines. The reactogenicity of whole-cell pertussis vaccines is, to a large extent, derived from the lipid A moiety of the lipopolysaccharides (LPS) of the bacteria. Here, we engineered B. pertussis strains with altered lipid A structures by expressing genes for the acyltransferases LpxA, LpxD, and LpxL from other bacteria resulting in altered acyl-chain length at various positions. Whole cells and extracted LPS from the strains with shorter acyl chains showed reduced or no activation of the human Toll-like receptor 4 in HEK-Blue reporter cells, whilst a longer acyl chain increased activation. Pyrogenicity studies in rabbits confirmed the in vitro assays. These findings pave the way for the development of a new generation of whole-cell pertussis vaccines with acceptable side effects.

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“…B. pertussis is the causative agent of whooping cough, which has reemerged as a public health threat despite broad vaccine coverage. The re-emergence of this pathogen has been correlated with the transition from the use of whole-cell pertussis vaccines to acellular component vaccines (Bart et al ., 2014; Melvin et al ., 2014) which usually contain up to 5 purified B. pertussis antigens, namely the pertussis toxin, (PT), Filamentous Hemagglutinin (FHA), Pertactin (PRN) and Fimbriae (FIM2 and FIM3) (Dewan et al ., 2020). Among this, the pertactin, a highly immunogenic outer membrane protein that promotes adhesion to tracheal epithelial cells (Inatsuka et al ., 2010), has been implicated in vaccine-driven evolution presenting different types of knock-out mutations in circulating strains.…”

Section: Resultsmentioning

confidence: 99%

Easy identification of insertion sequence mobilization events in related bacterial strains with ISCompare

Mogro

Ambrosis

Lozano

2020

Preprint

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Motivation: Bacterial genomes are composed by a core and an accessory genome. The first composed of housekeeping and essential genes, while the second is composed, in its majority, of mobile genetic elements, including transposable elements (TEs). Insertion sequences (ISs), the smallest TEs, have an important role in genome evolution, and contribute to bacterial genome plasticity and adaptability. ISs can spread in a genome, presenting different locations in nearly related strains, and producing phenotypic variations. Few tools are available which can identify differentially located ISs (DLIS) on assembled genomes. Results: We developed ISCompare to profile IS mobilization events in related bacterial strains using complete or draft genome assemblies. ISCompare was validated using artificial genomes with simulated random IS insertions and real sequences, achieving the same or better results than other available tools, with the advantage that ISCompare can analyse multiple ISs at the same time and outputs a list of candidate DLIS. We think that ISCompare provides an easy and straightforward approach to look for differentially located ISs on bacterial genomes. Availability and implementation: ISCompare was implemented in python3 and its source code is freely available for download at https://github.com/maurijlozano/ISCompare. Supplementary information: Supplementary data are available at Bioinformatics online.

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Acellular Pertussis Vaccine Components: Today and Tomorrow

Cited by 33 publications

References 84 publications

Modeling Immune Evasion and Vaccine Limitations by Targeted Nasopharyngeal Bordetella pertussis Inoculation in Mice

Modeling Immune Evasion and Vaccine Limitations by Targeted Nasopharyngeal Bordetella pertussis Inoculation in Mice

Shortening the Lipid A Acyl Chains of Bordetella pertussis Enables Depletion of Lipopolysaccharide Endotoxic Activity

Easy identification of insertion sequence mobilization events in related bacterial strains with ISCompare

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