Lot-to-lot consistency of a hexavalent DTwP-IPV-HB-PRP∼T vaccine and non-inferiority to separate DTwP-HB-PRP∼T and IPV antigen-matching vaccines at 6–8, 10–12, and 14–16 weeks of age co-administered with oral rotavirus vaccine in healthy infants in India: A multi-center, randomized, controlled study

BACKGROUND: Combination vaccines reduce the number of pediatric injections but must be as safe, immunogenic, and effective as each of the individual vaccines given separately. Additionally, consistency in manufacturing lots is essential for WHO prequalification. This study aimed to establish the lot-to-lot consistency of a fully liquid, hexavalent diphtheria (D)-tetanus (T)-whole-cell pertussis (wP)-inactivated poliovirus (IPV)-hepatitis B (HB)-Haemophilus influenzae b (PRP-T) (DTwP-IPV-HB-PRP∼T) vaccine and to demonstrate non-inferiority to licensed DTwP-HB-PRP∼T and IPV vaccines. METHODS: A Phase III, randomized, active-controlled, and open-label study was conducted at multiple centers across India. Healthy infants who had received a birth dose of oral poliovirus vaccine and hepatitis B vaccine received one of three lots of DTwP-IPV-HB-PRP∼T or separate DTwP-HB-PRP∼T and IPV vaccines at 6–8, 10–12, and 14–16 weeks of age. Oral rotavirus vaccine was co-administered at 6–8 weeks of age and 10–12/14–16 weeks of age. DTwP-IPV-HB-PRP∼T lot-to-lot consistency and non-inferiority (pooled DTwP-IPV-HB-PRP∼T) versus DTwP-HB-PRP∼T and IPV post-third dose were assessed using seroprotection rates (anti-D, anti-T, anti-HBs, anti-PRP, anti-polio 1, 2, 3) and adjusted geometric mean concentrations (anti-PT, anti-FIM). Safety was assessed by parental reports. RESULTS: Lot-to-lot consistency was demonstrated for DTwP-IPV-HB-PRP∼T and non-inferiority versus DTwP-HB-PRP∼T and IPV was confirmed with 95% CIs for seroprotection rate differences and adjusted geometric mean concentration ratios within pre-defined clinical margins. Pooled seroprotection rate was ≥ 99.7% for anti-D ≥ 0.01 IU/mL, anti-T ≥ 0.01 IU/mL, anti-HBs ≥ 10 mIU/mL, anti-PRP ≥ 0.15 µg/mL, and anti-polio 1, 2, and 3 ≥ 8 (1/dil) and vaccine response rate was 83.9% for anti-PT and 97.7% for anti-FIM. There were no safety concerns. CONCLUSIONS: Immunogenicity of three lots of the fully liquid DTwP-IPV-HB-PRP∼T vaccine was consistent and non-inferior to licensed comparators following vaccination at 6–8, 10–12, and 14–16 weeks of age. There were no safety concerns and no evidence of any effect of co-administration with rotavirus vaccine.