Resurgence of pertussis calls for re-evaluation of pertussis animal models

Aa, van der Ark; Hozbor, Daniela Flavia; Cj, Boog; Metz, Bernard; Gp, van den Dobbelsteen; Ca, van Els

doi:10.1586/erv.12.83

Cited by 30 publications

(27 citation statements)

References 127 publications

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“…Regardless of the reasons for this recent increase in pertactindeficient isolates in the United States, clinical information, in vivo functional assays, animal modeling, and vaccine effectiveness studies are crucial not only for understanding the clinical implications of these changes but also for helping to develop and test new vaccine formulations (34). Vigilant monitoring of the cellular and molecular changes of not only B. pertussis but also other Bordetella spp., via bacterial isolation and molecular methods, is critical for determining the next steps for protecting the health of the public against these highly contagious pathogens.…”

Section: Discussionmentioning

confidence: 99%

Prevalence and Molecular Characterization of Pertactin-Deficient Bordetella pertussis in the United States

Pawloski

Queenan

Cassiday

et al. 2013

Clin. Vaccine Immunol.

182

165

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Section: Discussionmentioning

confidence: 99%

Prevalence and Molecular Characterization of Pertactin-Deficient Bordetella pertussis in the United States

Pawloski

Queenan

Cassiday

et al. 2013

Clin. Vaccine Immunol.

182

165

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“…Nevertheless, using a (naive) murine model has several advantages. It is regarded an important small animal model for pertussis vaccine development [105] and enables to dissect the local and systemic immune response in great detail, as shown in this study, rather than using blood or nasal washes from humans undergoing a B. pertussis infection. Furthermore, the role of individual gene signatures and products could be assessed in future research in mice by using knockin or knockout strains, or by functional interventions.…”

Section: Discussionmentioning

confidence: 99%

Molecular Signatures of the Evolving Immune Response in Mice following a Bordetella pertussis Infection

et al. 2014

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Worldwide resurgence of pertussis necessitates the need for improvement of pertussis vaccines and vaccination strategies. Since natural infections induce a longer-lasting immunity than vaccinations, detailed knowledge of the immune responses following natural infection can provide important clues for such improvement. The purpose was to elucidate the kinetics of the protective immune response evolving after experimental Bordetella pertussis (B. pertussis) infection in mice. Data were collected from (i) individual analyses, i.e. microarray, flow cytometry, multiplex immunoassays, and bacterial clearance; (ii) twelve time points during the infection; and (iii) different tissues involved in the immune responses, i.e. lungs, spleen and blood. Combined data revealed detailed insight in molecular and cellular sequence of events connecting different phases (innate, bridging and adaptive) of the immune response following the infection. We detected a prolonged acute phase response, broad pathogen recognition, and early gene signatures of subsequent T-cell recruitment in the lungs. Activation of particular transcription factors and specific cell markers provided insight into the time course of the transition from innate towards adaptive immune responses, which resulted in a broad spectrum of systemic antibody subclasses and splenic Th1/Th17 memory cells against B. pertussis. In addition, signatures preceding the local generation of Th1 and Th17 cells as well as IgA in the lungs, considered key elements in protection against B. pertussis, were established. In conclusion, molecular and cellular immunological processes in response to live B. pertussis infection were unraveled, which may provide guidance in selecting new vaccine candidates that should evoke local and prolonged protective immune responses.

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“…A comprehensive review on these animal models has recently been published by van der Ark et al [13]. The routine batch release control test required by regulatory bodies can be different from the assays used for research and development in a number of ways.…”

Section: Abstract: Intracerebral Mouse Protection Test • Kendrick Tesmentioning

confidence: 99%

Whole-cell pertussis vaccine potency assays: the Kendrick test and alternative assays

Xing

Markey

Das

et al. 2014

Expert Review of Vaccines

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Whole-cell pertussis vaccines are still widely used across the globe and have been shown to produce longer lasting immunity against pertussis infection than acellular pertussis vaccines. Therefore, whole-cell vaccines are likely to continue to be used for the foreseeable future. The intracerebral mouse protection test (Kendrick test) is effective for determining the potency of whole-cell pertussis vaccines and is the only test that has shown a correlation with protection in children. Here we review the Kendrick test in terms of international requirements for vaccine potency and critical technical points to be considered for a successful test including test validity, in-house references and statistical analysis. There are objections to the Kendrick test on animal welfare and technical grounds. Respiratory challenge assays, nitric oxide induction assay and serological assays have been developed and have been proposed as possible methods which might provide alternatives to the Kendrick test. These methods and their limitations are also briefly discussed. Establishment of validated in vitro correlates of protection has yet to be achieved. New technical developments, such as genome sequence and the use of gene microarrays to screen responses triggered by vaccine components may also provide leads to alternative assays to the Kendrick test by identifying biomarkers of protection.

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Resurgence of pertussis calls for re-evaluation of pertussis animal models

Cited by 30 publications

References 127 publications

Prevalence and Molecular Characterization of Pertactin-Deficient Bordetella pertussis in the United States

Prevalence and Molecular Characterization of Pertactin-Deficient Bordetella pertussis in the United States

Molecular Signatures of the Evolving Immune Response in Mice following a Bordetella pertussis Infection

Whole-cell pertussis vaccine potency assays: the Kendrick test and alternative assays

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