Clinical evaluation for batch consistency of an inactivated enterovirus 71 vaccine in a large-scale phase 3 clinical trial

Hum Vaccin Immunother. 2014;10(5):1366-72. doi: 10.4161/hv.28397. Epub 2014 Mar 14.

Abstract

The demonstration of batch-to-batch consistency to confirm the reliability of the manufacturing process has become a mandatory step in vaccine development. This is a post-hoc analysis aimed to provide more solid evidence on the immunogenicity and consistency of 3 consecutive batches of a novel inactivated enterovirus 71 (EV71) vaccine. In total 10 245 healthy Chinese children aged 6-35 months had been recruited and randomized to receive one of 3 batches of EV71 vaccine or placebo according to a two-dose immunization schedule in a phase 3 clinical trial. Blood samples were taken just before and 28 days after vaccinations for serological tests of EV71 neutralizing antibody (NTAb) titer from the subjects. Among them, 7263 (70.9%) subjects with seronegative EV71 NTAb at baseline and the data of serological tests post-vaccination available were included for the analysis. The results showed that EV71 vaccine elicited high geometric mean titers (GMTs) of 407.0 U/mL (95% CI, 373.5-443.6) for batch 1, 468.1 U/mL (95% CI, 432.2-507.0) for batch 2, and 520.6 U/mL (95% CI, 481.2-563.3) for batch 3. The two-sided 95% confidence intervals (CIs) for the GMT ratios between each pair of vaccine batches were all within an interval of [0.67, 1.5]. Subjects who received EV71 vaccines demonstrated significant higher GMTs than those received placebos did (P<0.001). In terms of incidence of both local and general adverse reactions, no differences were found among 3 vaccine batches and placebos. EV71 vaccine was highly immunogenic in children, and the 3 consecutive batches were well consistent.

Keywords: batch consistency; enterovirus 71; immunogenicity; inactivated vaccine; safety.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Child, Preschool
  • Double-Blind Method
  • Drug Compounding / standards
  • Enterovirus A, Human / immunology*
  • Enterovirus Infections / immunology
  • Enterovirus Infections / prevention & control
  • Female
  • Humans
  • Infant
  • Male
  • Reproducibility of Results
  • Vaccination / standards*
  • Vaccines, Inactivated / administration & dosage
  • Vaccines, Inactivated / immunology*
  • Vaccines, Inactivated / standards*

Substances

  • Vaccines, Inactivated