Are serological responses to acellular pertussis antigens sufficient criteria to ensure that new combination vaccines are effective for prevention of disease?

Combining several vaccines in a single formulation can alleviate the increasing complexity of the paediatric vaccination schedule. However, vaccine antigens that are highly effective when administered singly may lose potency in combination; consequently, the efficacy of each component must be established for any new proposed combination vaccine. When the serological response to a vaccine correlates clearly with clinical efficacy, the efficacy of that component in a combination can be inferred from immunogenicity studies. Poliovirus, tetanus and diphtheria toxoids, Haemophilus influenzae type b and Neisseria meningitidis, and hepatitis B vaccines, can all be assessed in this manner. Unfortunately, the antibody titres induced by acellular pertussis vaccines do not correlate with vaccine efficacy. Thus, although diphtheria-tetanus-acellular pertussis (DTaP) vaccine has been considered a prime building block in the development of new combination vaccines, modifying DTaP by the addition of new vaccine components may decrease the ability of the vaccine to protect against pertussis without a change in serum antibody response. For this reason, immunogenicity is not an adequate or safe basis for licensing combination vaccines containing acellular pertussis. Development and licensing of new combination vaccines containing components with serological correlates of clinical efficacy can proceed more rapidly than DTaP-based combinations and should be pursued.