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 licensed 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 licensed
vaccine controls.
Diphtheria and
tetanus antibody levels were substantially above protective levels in all study groups. The anti-HBs responses (% > or = 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 (% > or = 1.0 microg/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 licensed 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 licensed 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.