Approaches to the control of acellular pertussis vaccines.

The quality control of acellular pertussis vaccines presents particular problems related to the differences in composition and method of detoxification used in the various type of preparation. These vaccines are not amenable to potency assay by the active mouse protection test used for whole-cell pertussis vaccines and assurance of protective activity is problematic. In contrast, monitoring of these vaccines for safety is relatively straightforward and is centred on assays for the lipooligosaccharide endotoxin, active pertussis toxin and absence of reversion to toxicity of detoxified product. The absence of heat-labile toxin, tracheal cytotoxin and adenyl cyclase toxin is assumed provided that adequate validation of the process has been performed. Confirmation of the antigenic content of the detoxified bulk components is difficult to achieve by conventional binding assays based on monoclonal antibodies because of changes in accessibility of reactive sites post-toxoiding. However, single radial diffusion assay using polyclonal antisera permits estimation of pertussis toxoid (PT), filamentous haemagglutinin (FHA) and pertactin (P69). Dot blot immunoassay can be used for the fimbrial agglutinogens 2 and 3 (Fim 2 and 3) and potentially could also be used to check the composition of final filling lots for PT, FHA, P69 and Fim 2 and 3. Gel electrophoresis and immunoblotting can be applied to monitor purity of purified bulk components and the characteristics of these change after chemical detoxification. Electron microscopy provides a useful semi-quantitative supporting method for checking purity of bulk components. Physico-chemical examination, particularly CD and fluorescence spectroscopy, offer a means of monitoring the consistency of detoxified bulk components. No completely satisfactory method is available for monitoring potency. Immunogenicity assays may be useful for checking consistency but do not necessarily correlate with protection. At present, active protection against aerosol challenge offers the best prospect of a functional assay.