Animal models are used for the evaluation of the safety and immunogenicity of acellular pertussis vaccines before administration to humans. The aerosol challenge model provides a reproducible system for the study of virulence factors and immunity involved in respiratory infection and subsequent disease. Clinical studies have shown that acellular pertussis antigens are protective against disease; however, to date, there is no laboratory correlate of vaccine mediated protection. In some recent publications, authors have suggested that when mice were immunized with DTP vaccines [with either whole-cell or acellular pertussis component] and then challenged with an aerosol or intranasal B. pertussis, the clearance of infection from the lungs paralleled the ability of these vaccines to protect children against pertussis. The aerosol model has been evaluated in our laboratory; despite excellent intra- and inter-assay reproducibility, the rate of bacterial clearance does not distinguish between mice immunized with vaccines of high and low clinical efficacy. Preliminary evidence in our and other laboratories suggests that the intranasal challenge may have a greater potential to distinguish between mice immunized with whole cell DTP vaccines of known higher and lower clinical efficacy. We are currently participating in an international, multi-center evaluation of DTP vaccines to evaluate various animal challenge models to determine whether any may provide a laboratory correlate of protection. If the observations can be verified, the model could be used to evaluate changes in manufacturing of new combination vaccines. Additionally, the model could be used to determine whether an immunization schedule that includes vaccines from more than one manufacturer is as efficacious as a schedule that uses vaccine from a singe manufacturer.
