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Updated: Sep 5, 2025
Use of Viral Entry Assays and Molecular Docking Analysis for the Identification of Antiviral Candidates against Coxsackievirus A16
Published on: July 15, 2019
Development and evaluation of an inactivated coxsackievirus A16 vaccine in gerbils
Yi-Sheng Sun1, Yong Xia1, Fang Xu1
1Key Lab of Vaccine, Prevention and Control of Infectious Disease of Zhejiang Province, Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, People's Republic of China.
Insights
A new Coxsackievirus A16 (CVA16) vaccine candidate, CVA16-393, shows promise for preventing hand, foot, and mouth disease (HFMD). This MRC-5 adapted strain induced effective neutralizing antibodies and cross-protection in animal models.
Area of Science:
- Virology
- Vaccinology
- Pediatric infectious diseases
Background:
- Coxsackievirus A16 (CVA16) is a primary cause of hand, foot, and mouth disease (HFMD), particularly affecting children in Asia.
- Currently, no licensed CVA16 vaccine is available for human use, highlighting an urgent need for preventative strategies.
Purpose of the Study:
- To develop and evaluate a CVA16 vaccine candidate strain adapted for high-growth replication in MRC-5 cells.
- To assess the immunogenicity and protective efficacy of an inactivated whole-virus vaccine derived from the candidate strain.
Main Methods:
- Isolation and adaptation of a high-growth CVA16 strain (CVA16-393) in MRC-5 cells through plaque purification.
- Production of an inactivated whole-virus vaccine from the CVA16-393 strain.
- Evaluation of vaccine efficacy in gerbils, including assessment of neutralizing antibody responses and cross-protection against diverse CVA16 strains.
Main Results:
- The CVA16-393 strain, belonging to subgenotype B1b, achieved high titers (>10^7 TCID50/ml) in MRC-5 cells with stable VP1 gene sequences.
- The inactivated vaccine induced significant neutralizing antibody responses in gerbils after two doses.
- A CVA16 vaccine dose above 25 U provided 100% cross-protection against lethal challenges with five different Chinese CVA16 clinical strains.
Conclusions:
- The CVA16-393 strain is a promising candidate for developing an effective CVA16 vaccine.
- The vaccine demonstrated robust immunogenicity and broad cross-protective capabilities in preclinical studies.
- Further development of this vaccine could offer a vital tool for controlling CVA16-induced HFMD in children.
Abstract:
Coxsackievirus A16 (CVA16) is one of the major pathogens responsible for human hand, foot, and mouth disease (HFMD), which has threatened the health of young children, particularly in Asia-Pacific nations. Vaccination is an effective strategy for protecting children from CVA16 infection. However, there is currently no licensed CVA16 vaccine for use in humans. In this study, we isolated a high-growth CVA16 virus strain in MRC-5 cells and developed an MRC-5-adapted vaccine candidate strain termed CVA16-393 via two rounds of plaque purification. The CVA16-393 strain was grouped into the B1b subgenotype and grew to a titre of over 107 TCID50/ml in MRC-5 cells. The VP1 gene region of this strain, which contains the major neutralizing epitopes, displayed high stability during serial passages. The inactivated whole-virus vaccine produced by the CVA16-393 strain induced an effective neutralizing antibody response in Meriones unguiculatus (gerbils) after two doses of intraperitoneal inoculation. One week after the booster immunization, the geometric mean titres of the neutralizing antibodies for the 10246, 40812TXT, 11203SD, TJ-224 and CA16-194 strains from different regions of China were 137.8, 97.8, 113.4, 64.1 and 122.3, respectively. A CVA16 vaccine dose above 25 U was also able to provide 100% cross-protection against lethal challenges with these five clinical strains in gerbils. Immunization at a one-week interval could maintain a high level of neutralizing antibody titres for at least 8 weeks. Thus, the vaccine produced by this CVA16-393 strain might be promising.
