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

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: :

• enterovirus 71
• inactivated vaccine
• batch consistency
• immunogenicity
• safety

10.4161/hv.28397

Disclosure of Potential Conflicts of Interest

X.-L.L., Y.-T.Z., Q.-H.C., and H.-J.G. are employees of National Engineering Research Center of Innovative Vaccine of Beijing Vigoo Biological Co., Ltd. Other authors claimed that they have no conflicts of interest.

The study was co-funded by China 12–5 National Major Infectious Disease Programs (2012ZX10004-703 and 2012ZX10002-001), and Beijing Vigoo Biological Co., Ltd.

Acknowledgments

We thank all the investigators from Jiangsu Provincial Center for Disease Control and Prevention, National Institute for Food and Drug Control, Donghai County Center for Disease Control and Prevention, Pizhou County Center for Disease Control and Prevention, Baoying County Center for Disease Control and Prevention, and Chaoyang District Center for Disease Control and Prevention.