Clinical experience shows DTPw-HBV/Hib combination vaccines to be an efficient and reliable method of implementing WHO recommendations for controlling diphtheria, tetanus, pertussis, hepatitis B and Hib infections on a worldwide basis . For the new vaccine evaluated in this study, new antigen sources and reduced antigen content were used to ensure continued vaccine supply for global mass vaccination campaigns. This DTPw-HBV/Hib combination vaccine is based on the same formulation as the licensed Tritanrix™-HBV/Hib vaccine [12, 20], but containing diphtheria, tetanus and pertussis antigens from an alternative source and a lower amount of the PRP capsular polysaccharide component of Hib (2.5 instead of 10 μg/mL per 0.5 ml dose). The study was designed and powered for immunogenicity comparison in primary vaccination; booster evaluation was purely descriptive and conducted in a limited proportion of initially primed subjects. Co-administered with OPV at 2, 4 and 6 months of age, the new DTPw-HBV/Hib vaccine was found to be non-inferior to Tritanrix™-HBV/Hib in terms of seroprotection to the D, T, HBs and PRP vaccine antigens one month after completion of the 3-dose primary course. Immune response to all vaccine antigens was within the range previously reported for this or other similar DTPw-based vaccines [11–13, 15–17, 20].
Lot-to-lot consistency for the new DTPw-HBV/Hib vaccine was demonstrated, i.e., for anti-diphtheria, anti-tetanus, anti-HBs and anti-PRP, the standardized asymptotic 90% confidence intervals (CI) for the absolute difference between each pair of lots in the percentage of subjects seroprotected was within [-10%; 10%] and for anti-BPT, the 90% confidence interval for the ratio of geometric mean antibody concentrations (GMCs) between each pair of lots was within [0.5, 2] (data not shown). Based on these findings, data for the three vaccine lots used in this study were pooled for comparison against the control vaccine.
Antibody GMCs induced by the new DTPw-HBV/Hib vaccine following primary vaccination were observed similar to those induced by Tritanrix™-HBV/Hib, with the exception of anti-PRP GMC. However, almost all subjects achieved anti-PRP concentrations ≥1.0 μg/mL (≥97.3%) and post-primary anti-PRP GMCs were high (> 12.5 μg/mL) in both groups, suggesting that intergroup differences are unlikely to be of clinical relevance. A large body of evidence shows reduction of the PRP content of Hib conjugate-based vaccines to have no negative impact on either immune response or induction of immune memory to Hib [21–26]. Effective induction of immune memory was demonstrated with the reduced-content Hib component used in this DTPw-HBV/Hib vaccine [14, 18]. In our study, a high degree of antibody persistence and a vigorous booster response was seen for all vaccine antigens including PRP in both groups, indicative of effective priming and induction of immune memory with both vaccines.
The new DTPw-HBV/Hib vaccine was found to have an acceptable reactogenicity profile. Some differences in reactogenicity were observed between the two vaccines. However, since very few subjects in either group sought medical advice for solicited symptoms it is likely that any differences had minimal clinical impact. Also, as no correction for multiplicity of endpoints was applied, statistically significant differences in reactogenicity should be interpreted with caution. Very few subjects in this study failed to receive all planned vaccine doses due to adverse events (2 in the DTPw-HBV/Hib group and 1 in the Tritanrix™-HBV/Hib group). Indeed, by eliminating the need for multiple injections, such combination vaccines are likely to promote compliance with infant immunization schedules [2–4]. In both groups, the incidence of solicited symptoms was higher after the booster dose than after the primary doses, as has previously been reported following booster vaccination with DTPw- and diphtheria-tetanus-acellular pertussis based vaccines [14, 15, 17, 27, 28].