Diphtheria-tetanus-pertussis (DTP) combination vaccines based on inactivated whole-cell Bordetella pertussis (DTPw) or purified acellular pertussis components (DTPa) facilitate vaccine administration and will allow further co-administration such as with pneumococcal conjugates. Safety and immunogenicity studies are needed to demonstrate non-inferiority between combinations and the separate vaccines. The immunological non-inferiority is based on threshold antibody levels that represent correlates of protection. However, in case of pertussis, correlates of protection have not been defined or accepted. We describe the clinical evaluation of DTPa- and DTPw-based combinations and demonstrate their immunological non-inferiority as compared to their separately administered licensed counterparts. With respect to antibody responses against pertussis, a number of evaluations (vaccine response rates and geometric mean concentrations (GMCs) for anti-PT, anti-FHA, anti-PRN or anti-BPT; reverse cumulative distribution curves) are described. We also demonstrate that the B. pertussis mouse lung clearance model is able to predict clinical efficacy of licensed DTPa and DTPw vaccines and represents a useful tool to evaluate new combination vaccines.