Approaches to the control of acellular pertussis vaccines

The quality control of acellular pertussis vaccines presents particular pro blems related to the differences in composition and method of detoxificatio n 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 pe rtussis vaccines and assurance of protective activity is problematic; In contrast, monitoring of these vaccines for safety is relatively straight forward and is centred on assays for the lipooligosaccharide endotoxin, act ive pertussis toxin and absence of reversion to toxicity of detoxified prod uct. The absence of heat-labile toxin, tracheal cytotoxin and adenyl cyclas e toxin is assumed provided that adequate validation of the process has bee n performed. Confirmation of the antigenic content of the detoxified bulk components is difficult to achieve by conventional binding assays based on monoclonal ant ibodies because of changes in accessibility of reactive sites post-toxoidin g. However, single radial diffusion assay using polyclonal antisera permits estimation of pertussis toroid (PT), filamentous haemagglutinin (FHA) and pertactin (P69). Dot blot immunoassay can be used for the fimbrial agglutin ogens 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 Firn 2 and 3. Gel electrophoresis and immunoblotting can be applied to monitor purity of purified bulk components and the characteristics of these change after chem ical detoxification. Electron microscopy provides a useful semi-quantitativ e supporting method for checking purity of bulk components. Physico-chemica l 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. Immu nogenicity assays may be useful for checking consistency but do not necessa rily correlate with protection. At present, active protection against aeros ol challenge offers the best prospect of a functional assay. (C) 1999 The I nternational Association for Biologicals.