Discussion
diphtheria, tetanus
DIPHTHERIA, PERTUSSIS, PERTUSSIS, HEP B, HIB, TETANUS
This phase 3 study conducted in India evaluated the safety and immunogenicity in 460 infants followed up for 28 days after administration of three doses of either investigational or existing vaccine formulations of the SHIPL DTwP-HepB-Hib pentavalent vaccine at 6–8 weeks, 10–12 weeks and 14–16 weeks of age when administered concomitantly with other age-recommended vaccines.Both primary objectives were met in the study. The overall non-inferiority was demonstrated because the statistical tests concluded to the non-inferiority of the investigational DTwP-HepB-Hib formulation versus the comparator DTwP-HepB-Hib formulation at day 28 post-dose 3 for immune responses to both HepB and pertussis (PT and FIM) antigens contained in the vaccines. The immune responses to antigens of the five valences (D, T, HepB, Pertussis and Hib) at day 28 post-dose 3 were also observed to be similar in the investigational and comparator DTwP-HepB-Hib groups.Pre-immunization (day 0) anti-T seroprotection rates (i.e. ≥ 0.01 IU/mL) were observed to be 100% of subjects in both the groups. This was due to the presence of maternal antibodies and points to the highly successful maternal immunization program in India by which elimination of maternal and neonatal tetanus was achieved in 2015 [The anti-HBs seroprotective rates tended to be similar irrespective of whether the study subjects received HepB vaccination at birth or not. The results are similar to those observed in other HepB containing combination vaccine studies [The demonstration of the non-inferiority of the investigational DTwP-HepB-Hib vaccine formulation versus the licensed comparator DTwP-HepB-Hib vaccine formulation for their immune responses against Vaccination with either investigational or licensed comparator DTwP-HepB-Hib vaccine formulation was found to be well tolerated. The safety profile was found to be similar in both the investigational and comparator DTwP-HepB-Hib vaccine groups. There were no safety concerns observed during this study. As seen from previous studies, safety profile of investigational vaccine in the current study was not different from the safety profile of other pentavalent vaccines when evaluated in Indian infants [Limitation of this study were that it was conducted only in India, where Hep B vaccine is recommended at birth, so very few datapoints could be generated without a Hep B birth dose. The non-inferiority was assessed in the absence of demonstrated correlates of protection for some antigens, and therefore based on the data distribution.Our study highlights the importance of international collaboration for the development of multivalent vaccines. For our investigational pentavalent vaccine, 3 components (diphtheria, tetanus and HiB) are manufactured in India using standard technology; the hepB component was sourced from the manufacturing facility in Argentina, while the wP component was manufactured in India after successful technology transfer including the seed strains. This suggests that for the purpose of investigational vaccine development countries need not be limited by their geographical boundaries.Our results also add to the knowledge of evaluating and comparing immune responses to pertussis components in clinical trial settings, especially for wP containing combination vaccines. In the absence of well-defined correlates of serological protection and standardized assays or methods, the results from this study will provide guidance to researchers.