A combined liquid Hib (PRP-OMPC), hepatitis B, diphtheria, tetanus and whole-cell pertussis vaccine: controlled studies of immunogenicity and reactogenicity

Abstract

We evaluated the immunogenicity and reactogenicity of a new liquid pentavalent combination vaccine, which incorporates a diphtheria, tetanus and whole-cell pertussis vaccine (DTP) with Hib (PRP-OMPC) and hepatitis B vaccine (HB), in a series of three studies involving 2156 infants. The vaccination schedule was 2, 4, 6 and 18 months for all studies. In addition, subjects in the third study also received a dose of monovalent hepatitis B vaccine at birth. The principal study was a randomised double blind trial of two separate, but concurrently administered vaccines in each of three groups: pentavalent vaccine [DTP-Hib-HB] plus placebo (Group A, n=619); quadrivalent vaccine [DTP-HB] plus Hib vaccine (Group B, n=620); and bivalent vaccine [Hib-HB] plus DTP (Group C, n=226). The second study (Group D, n=231) was an open trial of three separate, but concurrently administered licenced control vaccines (DTP, Hib and HB). The third study (Group E, n=460) administered a dose of monovalent hepatitis B vaccine at birth followed by pentavalent vaccine as for Group A. Subjects were bled prior to the 2- and 18-month vaccinations, and a month after the 6- and 18-month vaccinations. A diary card was used to record subject temperatures and other systemic and local clinical signs for 7 days after each vaccination. The pentavalent vaccine, whether or not preceded by a birth dose of hepatitis B vaccine, was generally well tolerated at all administration times, and had a reactogenicity profile similar to that observed for licenced vaccine controls. Diphtheria and tetanus antibody levels were substantially above protective levels in all study groups. The anti-HBs responses (%≥10 mIU/ml) following the 6-month dose of vaccines were, respectively, for Groups A–E: 83.2, 91.7, 96.5, 98.8 and 93.9%, and following the 18-month doses: 87.9, 97.5, 98.8, 98.8 and 92.8%. Anti-PRP responses (%≥1.0 μg/ml) following the 6-month dose for Groups A–D were 86.0, 90.5, 91.2, and 74.4%, and after the 18-month dose for Groups A–E were 97.3, 98.3, 98.1, 97.0, and 99.5%. Consistently higher geometric mean titres (GMTs) for pertussis antibodies to agglutinogens (Agg2, Agg3) and pertactin were recorded for the pentavalent vaccine compared to the licenced control vaccine, though they were somewhat lower for pertussigen (PT). Except for the hepatitis B response, antibody responses induced by the pentavalent vaccine to all antigens with a schedule commencing at 2 months of age and completed at 18 months were equivalent to responses to the same antigens induced by the separate, but concurrently administered licenced control vaccines. A regimen of a birth dose of hepatitis B vaccine followed by pentavalent vaccine at 2, 4, 6 and 18 months was not countered by any clinically significant decrease in seroresponses.