Developments in pertussis vaccines leading to reduction and replacement of in vivo testing

The control of bacterial vaccines, in common with other biological products, requires that they conform to specified standards of purity, safety and efficacy. The specifications and the methods of assessment can vary between the different types of vaccines. Highly defined vaccines can be largely evaluated by physico-chemical methods. However, the control of whole-cell bacterial vaccines can be a very different proposition owing to the complex nature of the materials. Safety and efficacy testing of such products can involve number of in vivo assays. Our growing understanding of the pathogenesis of, and protective immune responses to, bacterial disease makes it possible to devise more effective and better-defined vaccines. In addition, it allows the the development of sensitive and precise in vitro assays. As a result, the requirement for in vivo control tests can be reduced and in some cases eliminated. This phenomenon is well illustrated by the recent advances in the development and control of pertussis vaccines. Certain in vitro tests, such as the LAL and CHO-cell assays, are proving valuable in checking for specific toxicities which can be associated with pertussis vaccines. Although some problems still exist in the development of a suitable potency assay for the acellular vaccines, as we gain more information on the contributions of the different aspects of the immune system towards protection from pertussis, the prospects for further improvements in both the vaccine and its control evaluation are promising.