Optimization and characterization of candidate strain for coxsackievirus A16 inactivated vaccine

Jingliang Li, Guanchen Liu, Xin Liu, Jiaxin Yang, Junliang Chang, Wenyan Zhang, Xiao Fang Yu

Research output: Contribution to journalArticlepeer-review

Abstract

Coxsackievirus A16 (CA16) and enterovirus 71 (EV71), both of which can cause hand, foot and mouth disease (HFMD), are responsible for large epidemics in Asian and Pacific areas. Although inactivated EV71 vaccines have completed testing in phase III clinical trials in Mainland China, CA16 vaccines are still under development. A Vero cell-based inactivated CA16 vaccine was developed by our group. Screening identified a CA16 vaccine strain (CC024) isolated from HFMD patients, which had broad cross-protective abilities and satisfied all requirements for vaccine production. Identification of the biological characteristics showed that the CA16CC024 strain had the highest titer (107:5 CCID50/mL) in Vero cells, which would benefit the development of an EV71/CA16 divalent vaccine. A potential vaccine manufacturing process was established, including the selection of optimal time for virus harvesting, membrane for diafiltration and concentration, gel-filtration chromatography for the down-stream virus purification and virus inactivation method. Altogether, the analyses suggested that the CC-16, a limiting dilution clone of the CC024 strain, with good genetic stability, high titer and broad-spectrum immunogenicity, would be the best candidate strain for a CA16 inactivated vaccine. Therefore, our study provides valuable information for the development of a Vero cell-based CA16 or EV71-CA16 divalent inactivated vaccine.

Original languageEnglish (US)
Pages (from-to)3891-3909
Number of pages19
JournalViruses
Volume7
Issue number7
DOIs
StatePublished - Jul 17 2015

Keywords

  • Coxsackievirus A16
  • HFMD
  • Inactivated vaccine
  • Vaccine candidate strain

ASJC Scopus subject areas

  • Infectious Diseases
  • Virology

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