The mouse intranasal challenge model for potency testing of whole-cell pertussis vaccines

Abstract

Introduction: A mouse intracerebral challenge model is used for potency testing of whole-cell pertussis (wP) vaccines. We investigated the use of a mouse nasopharyngeal challenge model, which better reflects the clinical features of pertussis disease, to differentiate between efficacy of wP vaccines. Methods: Efficacy of three wP vaccines (Quinvaxem^®, Easyfive^® and Pentavac^®) was tested in the nasopharyngeal challenge model. Mice were vaccinated at 4 and 7 weeks and challenged with Bordetella pertussis at 9 weeks. Vaccine efficacy was determined based on CFU in the lungs 5 days after challenge. Results: The mouse nasopharyngeal challenge model has the capacity to differentiate between the efficacy of whole cell pertussis vaccines. Conclusion: The mouse nasopharyngeal challenge model could be considered as a potency and release assay for wP vaccines. Whether this model directly correlates with clinical vaccine efficacy requires further investigations. Whether this model directly correlates with clinical vaccine efficacy requires further investigations. The mouse nasopharyngeal challenge model could be considered as a potency and release assay for wP vaccines.

Keywords::

• Bordetella pertussis
• Kendrick test
• mouse nasopharyngeal challenge model
• vaccine release assay
• whole cell pertussis vaccine

Acknowledgements

This work was performed by employees of Crucell Holland B.V, one of the Janssen Pharmaceutical Companies of Johnson & Johnson, department of Bacterial Vaccines Research and Development in Leiden, The Netherlands and employees of Janssen Pharmaceutical Research and Development, Spring House PA, USA. We thank J Melton for assistance with the animal studies.

Financial & competing interests disclosure

The work was funded by Crucell Holland B.V laboratory work was performed by Janssen Pharmaceutical Research and Development in Spring House PA, USA. AM Queenan, J Fernandez and W Shang are employees of Janssen Pharmaceutical Research and Development. SP Wiertsema, G van den Dobbelsteen and J Poolman are employees of Crucell Holland B.V, one of the Janssen Pharmaceutical Companies of Johnson & Johnson. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Whole-cell pertussis (wP) vaccines have been used for over 60 years, are safe and recommended for use in the developing world by the WHO.

• The wP vaccines are released based on a mouse intracerebral challenge model, which can demonstrate manufacturing consistency, but does not necessarily correlate with clinical efficacy. A mouse nasopharyngeal challenge model, which better reflects the clinical features of pertussis disease, has also been developed.

• We showed that the mouse nasopharyngeal challenge model has the capacity to differentiate between the efficacy of wP vaccines. This test could therefore be considered as a potency test and vaccine release assay of wP vaccines.

Notes