Immunogenicity and safety of a new liquid hexavalent combined vaccine compared with separate administration of reference licensed vaccines in infants

Objective, The immunogenicity and safety of a new liquid hexavalent vaccine (diphtheriatetanus-acellular pertussis-inactivated polio vaccine-hepatitis B-polyribosyl ribitol phosphate conjugated to tetanus protein; Hexavac; Av entis Pasteur MSD, Lyon, France) are compared with those of reference vacci nes [diphtheria-tetanusacellular pertussis-inactivated polio vaccine recons tituting lyophilized purified Haemophilus influenzae polysaccharide conjuga ted to tetanus protein vaccine (Pentavac; Aventis Pasteur MSD) and hepatiti s B vaccine (H-B-Vax II; Aventis Pasteur MSD)] injected separately at the s ame visit in a prospective multicenter, comparative, open label trial. Methods. Infants were randomized to receive Hexavac (n = 423) or Pentavac a nd H-B-Vax II (n = 425) as a primary immunization series at 2, 4 and 6 mont hs of age. Seroprotection and seroconversion rates against all antigens at 1 month after the primary series were compared between the two vaccine grou ps with 95% confidence intervals (CI0.95) and were considered clinically eq uivalent (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 equ ivalence to Pentavac and H-B-Vax II given concomitantly, It elicited simila r seroprotection and seroconversion rates against all antigens. Seroprotect ion and seroconversion rates obtained 1 month after the third dose of Hexav ac were >90% for all antigens. The postimmunization antibody geometric mean titers (GMT) for hepatitis B and purified Haemophilus influenzae polysacch aride were about a-fold higher in infants who received the reference vaccin es than in infants who had received Hexavac. GMTs for poliovirus antibodies tended to be enhanced in infants vaccinated with Hexavac. GMTs for all oth er antigens were very similar among both groups, Hexavac was generally well -tolerated, At least one local reaction was reported in 20.3% of Hexavac in jections compared with 15.8% at the Pentavac injections site and 3.8% at th e H-B-Vax II injections site. These reactions were generally mild and trans ient. 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 freq uency 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.