Toxicity and potency evaluation of pertussis vaccines.

Current methods for determining the potency and toxicity of pertussis vaccines are outdated and require improvement. The intracerebral challenge test is effective for determining the potency of whole-cell vaccines but is objectionable on animal welfare and technical grounds. The same applies to its modification for assaying acellular pertussis vaccines. Respiratory challenge methods offer an interim solution pending establishment of validated in vitro correlates of protection, for example nitric oxide induction. Their evaluation is being promoted by the World Health Organization through the Pertussis Vaccines Working Group. Current toxicity assays based on weight gain and histamine sensitization of mice are imprecise and need replacement. Limits need to be established for specific toxin content of both acellular and whole-cell vaccines and should be supported by specific assays. More precise methods based on determination of ribosyltransferase activity in tandem with receptor-binding assays are under evaluation. Genome sequence data and the use of gene microarrays to screen responses triggered by vaccine components may also provide leads to improved methods for assessing both toxicity and immunogenicity.