Safety and immunogenicity of Haemophilus influenzae type b-tetanus toxoid conjugate, presented in a dual-chamber syringe with diphtheria-tetanus-pertussis and inactivated poliomyelitis combination vaccine

The safety and immunogenicity of combining two established vaccines, polyribosyl ribitol phosphate conjugated to tetanus toxoid (PRP-T) (ActHIB, Pasteur Mérieux Connaught, Lyon, France) and diphtheria-tetanus-whole cell pertussis and inactivated poliovirus vaccine (DTP-IPV) (Tetracoq, Pasteur Mérieux Connaught, Lyon, France) were evaluated using a new dual-chamber syringe delivery system. Results were compared with those obtained when the two combination vaccines were either administered separately (two sites) or reconstituted manually and injected at a single site. A total of 487 2-month-old infants were enrolled in this study by 61 paediatricians in France. Infants were randomised to receive three immunisations of PRP-T and DTP-IPV at 2, 3 and 4 months of age, given either with the dual-chamber syringe (n = 213), as separate injections (n = 215), or as a single manually reconstituted injection (n = 59). Blood samples were taken prior to the first immunisation and 4 weeks after the third immunisation for the measurement of antibody titres. Infants were monitored by the parents for 3 days after each immunisation to detect local and systemic reactions. Local and systemic reactions occurring the 3 days following immunisation were as expected for the combination vaccines used. Safety of the vaccination using the dual-chamber syringe was as good as, if not slightly better than, that for the two vaccines administered separately. After the first immunisation, pain and unusual crying were significantly more frequent in infants who received two injections, compared to those who were immunised with the dual-chamber syringe. Serological responses were good for all antigens in the three groups and there was no evidence for any immunological interference. Almost all subjects in each group achieved levels of antibodies considered to be protective for all antigens. There were no clinically relevant differences in antibody response between any of the groups. The dual-chamber and separate injection methods of vaccination were equivalent according to a pre-defined criterion (percentage of infants with anti-PRP antibody titres ≥1.0 μg/ml).