To reduce the number of injections needed to comply with paediatric vaccination requirements, a liquid, hexavalent vaccine (DTaP-IPV-PRP-T-HBs; Hexavac; Aventis Pasteur MSD) has been developed for primary and booster vaccination of infants and toddlers. In extensive clinical studies, Hexavac has been shown to be highly immunogenic. Seroconversion or seroprotective titres of antibodies against all antigens were achieved in the majority of infants following a primary series of three doses administered at 1-2-month intervals from 2 months of age. Hexavac also induced immunologic memory, as evidenced by the anamnestic response to booster vaccination at 12-18 months of age. These responses were comparable with those seen following concomitant administration of Pentavac (DTaP-IPV//PRP-T) and monovalent hepatitis B vaccine (H-B-Vax II), and were also within the ranges observed for other relevant licensed vaccines. Clinical studies comparing the immunogenicity of Hexavac administered at either 2, 3 and 4 months or 2, 4 and 6 months demonstrated that it can be used by either vaccination schedule. A further study also supported the use of primary doses of Hexavac at 3 and 5 months with a booster at 12 months of age. Hexavac demonstrated a good reactogenicity and tolerability profile. The most frequently reported adverse events after both primary and booster doses were local reactions of redness and swelling/induration and a systemic response of mild fever, irrespective of the vaccine used for priming. Hexavac provided immunity against six important childhood diseases with a single injection at each visit.

Objective. The immunogenicity and safety of a new liquid hexavalent vaccine (diphtheria-tetanus-acellular pertussis-inactivated polio vaccine-hepatitis B-polyribosyl ribitol phosphate conjugated to tetanus protein; Hexavac; Aventis Pasteur MSD, Lyon, France) are compared with those of reference vaccines [diphtheria-tetanus-acellular pertussis-inactivated polio vaccine reconstituting lyophilized purified Haemophilus influenzae polysaccharide conjugated to tetanus protein vaccine (Pentavac; Aventis Pasteur MSD) and hepatitis B vaccine (H-B-Vax II; Aventis Pasteur MSD)] injected separately at the same visit in a prospective multicenter, comparative, open label trial. Methods. Infants were randomized to receive Hexavac (n = 423) or Pentavac and H-B-Vax II (n = 425) as a primary immunization series at 2, 4 and 6 months of age. Seroprotection and seroconversion rates against all antigens at 1 month after the primary series were compared between the two vaccine groups with 95% confidence intervals (CI0.95) and were considered clinically equivalent (not inferior) when the upper limit of the 95% confidence interval on the difference (reference, hexavalent) was below predefined differences. Results. Hexavac met and surpassed the predefined criteria for clinical equivalence to Pentavac and H-B-Vax II given concomitantly. It elicited similar seroprotection and seroconversion rates against all antigens. Seroprotection and seroconversion rates obtained 1 month after the third dose of Hexavac were >90% for all antigens. The postimmunization antibody geometric mean titers (GMT) for hepatitis B and purified Haemophilus influenzae polysaccharide were about 2-fold higher in infants who received the reference vaccines than in infants who had received Hexavac. GMTs for poliovirus antibodies tended to be enhanced in infants vaccinated with Hexavac. GMTs for all other antigens were very similar among both groups. Hexavac was generally well-tolerated. At least one local reaction was reported in 20.3% of Hexavac injections compared with 15.8% at the Pentavac injections site and 3.8% at the H-B-Vax II injections site. These reactions were generally mild and transient. At least one systemic adverse event was reported in 45.7% of Hexavac injections compared with 42.2% of Pentavac and H-B-Vax II injections (mild fever, irritability and drowsiness were most frequently reported). The frequency of adverse events was not significantly different between groups. No vaccine-related serious adverse event occurred during the study. Conclusion. This liquid hexavalent vaccine was generally well-tolerated and provided immune responses adequate to be protective against six infectious diseases with a single injection, given at 2, 4 and 6 months of age.