Diphtheria, tetanus, pertussis and hepatitis-B vaccine(GlaxoSmithKline Plc)

To support vaccination programs in developing countries, a 4-dose vial presentation of pneumococcal non-typeable Haemophilus influenzae protein D-conjugate vaccine (PHiD-CV) was developed. This study assessed immunologic non-inferiority and safety of the investigational PHiD-CV 4-dose versus licensed 1-dose vial presentation in infants.

In this phase III, mono-center, observer-blind study in Bangladesh, 6-10-week-old infants were randomized 1:1 to receive PHiD-CV primary vaccination (at ages 6, 10, 18 weeks) and a booster dose (at age 9 months) with a 4-dose vial (with preservative, 4DV group) or 1-dose vial (preservative-free, 1DV group). DTPw-HBV/Hib was (co)-administered per study protocol and polio, measles and rubella vaccines as part of the national immunization program. Non-inferiority of PHiD-CV 4-dose versus 1-dose vial for each vaccine pneumococcal serotype (VT) and vaccine-related serotype 19A in terms of antibody geometric mean concentration (GMC) was assessed (criterion: upper limit of 2-sided 95% confidence interval of antibody GMC ratios [1DV/4DV] <2-fold). Immune responses were measured. Solicited, unsolicited and serious adverse events (AEs) were evaluated.

Of 320 infants (160 per group) vaccinated during the primary vaccination phase, 297 received a booster. Non-inferiority was demonstrated for each VT and 19A. One month post-primary vaccination, for most VT, ≥97.9% of infants in each group had antibody concentrations ≥0.2 μg/mL; for 19A ≥ 80.1% reached this threshold. Pneumococcal antibody responses and opsonophagocytic activity for each VT and 19A were within similar ranges between groups after primary and booster vaccination, as were anti-protein D responses. Booster immune responses were observed in both groups. Reported AEs were within similar ranges for both presentations.

Immunologic non-inferiority of PHiD-CV 4-dose vial (with preservative) versus PHiD-CV 1-dose vial (preservative-free) was demonstrated. Immune responses and reactogenicity following primary/booster vaccination were within similar ranges for both presentations. PHiD-CV 4-dose vial would help improve access and coverage in resource-limited countries. Clinical Trial Registry: NCT02447432.

Hepatitis B and Haemophilus influenzae type b (Hib) infections are major public health problems in developing countries, including India. Hence, combination vaccines containing DTwP, recombinant hepatitis B and Hib conjugate vaccines have been developed. Here, we report a Phase IV study which assessed safety and reactogenicity of a new DTwP-HepB+Hib vaccine. Three doses of DTwP-HepB+Hib vaccine (Pentavac, Serum Institute of India Ltd) or Tritanrix-HB+Hib (GlaxoSmithKline Beecham) were administered to infants at 6, 10 and 14 weeks of age in 2:1 ratio. The subjects were followed till one month after the third dose for safety assessment. Adverse events were captured in structured diaries and physical examinations were performed on each visit. The study was conducted in 1510 infants. Both vaccines caused injection site local and systemic reactions and the incidence was similar in both the groups. The incidence of local solicited reactions was: tenderness 35.9 %-33.6 %; redness 18.1 %-17.2 %; swelling 23.7 %-22.4 %; induration 12.8 % -13.7 %. The percentage of systemic solicited reactions were: diarrhea 2.2 %-2.2 %; drowsiness 3.3 %-3.4 %; fever 14.0 %-11.2 %; irritability 28.1 %-25.4 %; loss of appetite 6.6 %-5.6 %; persistent crying 17.7 %-15.7 %; vomiting 3.5 %-3.0 %. No serious adverse event was caused by the vaccines. The new DTwP-HepB+Hib combination vaccine showed similar safety profile to that of an imported vaccine in Indian infants.