Combination vaccines containing DTPa-Hib: impact of IPV and coadministration of CRM 197 conjugates

Vaccination with diphtheria-tetanus-acellular pertussis (DTPa)-Haemophilus influenzae type b (Hib) combinations generally elicits anti-polyribosyl-ribitol-phosphate (PRP) antibody concentrations of more than 0.15 mu g/ml, a criterion that is linked to the protection of infants against Hib disease. In the UK, vaccination with DTPa3-Hib elicited atypically low anti-PRP antibody levels and was associated with breakthrough Hib cases. While the absence of a toddler booster is considered to be a key factor explaining the lowered control of Hib disease, we propose that the coadministration of serogroup C Neisseria meningitidis conjugate vaccine (MenC)-CRM197, which coincided with the introduction of DTPa3-Hib in the UK, may have played a role. However, other data suggest that the response to Hib after DTPa(HBV) inactivated polio vaccine (IPV)-Hib combinations is not affected by the coadministration of CRM197, which we postulate to be attributed to the presence of IPV. These observations underline the need to carefully evaluate upcoming pediatric conjugate vaccines for possible interference effects on the coadministered antigens, with particular attention to hepatitis B and Hib-tetanus toxoid.