title: 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.
authors.affiliation: School of Public Health; Southeast University; Nanjing, Jiangsu Province, PR China.
authors.forename: Yi-Juan
authors.initials: YJ
authors.lastname: Chen
authors.affiliation: Jiangsu Provincial Center for Disease Control and Prevention; Nanjing, Jiangsu Province, PR China.
authors.forename: Fan-Yue
authors.initials: FY
authors.lastname: Meng
authors.affiliation: National Institute for Food and Drug Control; Beijing, PR China.
authors.forename: Qunying
authors.initials: Q
authors.lastname: Mao
authors.affiliation: Jiangsu Provincial Center for Disease Control and Prevention; Nanjing, Jiangsu Province, PR China; College of Pharmacy; Third Military Medical University & National Engineering Research Center for Immunological Products; Chongqing, PR China.
authors.forename: Jing-Xin
authors.initials: JX
authors.lastname: Li
authors.affiliation: Jiangsu Provincial Center for Disease Control and Prevention; Nanjing, Jiangsu Province, PR China.
authors.forename: Hua
authors.initials: H
authors.lastname: Wang
authors.affiliation: National Institute for Food and Drug Control; Beijing, PR China.
authors.forename: Zheng-Lun
authors.initials: ZL
authors.lastname: Liang
authors.affiliation: Beijing Vigoo Biological Co., Ltd; Beijing, PR China.
authors.forename: Yun-Tao
authors.initials: YT
authors.lastname: Zhang
authors.affiliation: National Institute for Food and Drug Control; Beijing, PR China.
authors.forename: Fan
authors.initials: F
authors.lastname: Gao
authors.affiliation: Beijing Vigoo Biological Co., Ltd; Beijing, PR China.
authors.forename: Qing-Hua
authors.initials: QH
authors.lastname: Chen
authors.affiliation: Jiangsu Provincial Center for Disease Control and Prevention; Nanjing, Jiangsu Province, PR China.
authors.forename: Yuemei
authors.initials: Y
authors.lastname: Hu
authors.affiliation: School of Public Health; Nantong University; Nantong, Jiangsu Province, PR China.
authors.forename: Zi-Jun
authors.initials: ZJ
authors.lastname: Ge
authors.affiliation: National Institute for Food and Drug Control; Beijing, PR China.
authors.forename: Xin
authors.initials: X
authors.lastname: Yao
authors.affiliation: Beijing Vigoo Biological Co., Ltd; Beijing, PR China.
authors.forename: Hui-Jie
authors.initials: HJ
authors.lastname: Guo
authors.affiliation: Jiangsu Provincial Center for Disease Control and Prevention; Nanjing, Jiangsu Province, PR China.
authors.forename: Feng-Cai
authors.initials: FC
authors.lastname: Zhu
authors.affiliation: Beijing Vigoo Biological Co., Ltd; Beijing, PR China.
authors.forename: Xiu-Ling
authors.initials: XL
authors.lastname: Li
mesh_terms: D002675:Child, Preschool; D004311:Double-Blind Method; D004339:Drug Compounding / Q000592:standards; D029821:Enterovirus A, Human / Q000276:immunology*; D004769:Enterovirus Infections / Q000276:immunology / Q000517:prevention & control; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D015203:Reproducibility of Results; D014611:Vaccination / Q000592:standards*; D015164:Vaccines, Inactivated / Q000008:administration & dosage / Q000276:immunology* / Q000592:standards*
chemical_list: D015164:Vaccines, Inactivated
keywords: batch consistency; enterovirus 71; immunogenicity; inactivated vaccine; safety