Interchangeability of two Enterovirus 71 inactivated vaccines in Chinese children: A phase IV, open-label, and randomized controlled trial

Abstract

Background: In China, three inactivated Enterovirus 71 (EV71) vaccines have been approved. Although the vaccines in an immunization series should be from a single manufacture, children sometimes have to receive EV71 vaccines from more than one manufacturers. The aim of this study was to evaluate the interchangeability and safety of vaccination with EV71 vaccines from two manufacturers among Chinese children.

Methods: We conducted an open label and randomized controlled study among children aged 6-35 months from November 2018 to January 2019. The participants were randomly assigned (1:1:1:1) to receive EV71 vaccines in one of the four different schedules (two using a single vaccine for all doses from one manufacture, and two mixed schedules using vaccines from two manufactures). Blood samples were collected pre-vaccination (Day 0) and one month after the second dose (Day 60) for neutralizing antibody assay. Immunogenicity was assessed in the per-protocol cohort and safety was assessed in the total vaccinated cohort.

Results: A total of 300 children were enrolled and randomized, of whom 89.0% (267/300) were included in the per-protocol cohort for immunogenicity analysis. The seroconversion rates of the EV71 neutralizing antibody in four groups ranged from 98.4% to 100.0%, and were not significantly different among the groups. Compared with other groups, geometric mean titer was higher in group D, in which the participants received Institute of Medical Biology Chinese Academy of Medical Sciences (CAMS) vaccine in the first dose and the Sinovac vaccine in the second dose. Safety profiles were similar among the four groups and no serious adverse events related to the vaccination were reported.

Conclusions: Interchangeability of EV71 vaccines from two manufactures to complete an immunization series showed good immunogenicity and safety. The antibody response levels may vary by vaccination sequences of EV71 vaccines from the two manufacturers.

Trial registration: ClinicalTrials.govNCT03873740.

Keywords: EV71 vaccine; Immunogenicity; Interchangeability; Safety.