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

Abstract

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.

Keywords::

• intracerebral mouse protection test
• Kendrick test
• pertussis
• potency assay
• whole-cell pertussis vaccine

Financial & competing interests disclosure

This work was supported by NIBSC. 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

• A potency assay (that correlates with vaccine efficacy) is essential for quality assurance of whole-cell pertussis (wP) vaccine. The Kendrick test is the only internationally agreed official potency test for batch release control of wP vaccines or wP-based combination vaccines.

• wP vaccines shown to meet strictly the WHO requirements for intracerebral challenge assay were efficacious in clinical trials. Suitable standards are critical for this assay.

• Assay validation is essential and requires a good appreciation of the assay conditions, especially the choice of mouse strain, the ED₅₀ of immunization doses and the preparation of challenge strains (LD₅₀). It is important to consider the suitability of the reference materials and the assay conditions originally established for mono-component wP vaccines when applying the Kendrick assay to the evaluation of wP in combined vaccines.

• The Kendrick test has proved to be an effective potency test for wP vaccines, but, on the grounds of animal welfare and ease of performance, suitable alternative tests are urgently needed.