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Updated: Dec 29, 2025
Use of Viral Entry Assays and Molecular Docking Analysis for the Identification of Antiviral Candidates against Coxsackievirus A16
Published on: July 15, 2019
Identification of Antibodies with Non-overlapping Neutralization Sites that Target Coxsackievirus A16
Maozhou He1, Longfa Xu1, Qingbing Zheng1
1State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Sciences, School of Public Health, Xiamen University, Xiamen 361102, China.
Insights
Three neutralizing monoclonal antibodies show therapeutic potential against hand, foot, and mouth disease caused by coxsackievirus A16 (CVA16). These antibodies offer protection in mice and inform vaccine development strategies.
Area of Science:
- Virology
- Immunology
- Structural Biology
Background:
- Hand, foot, and mouth disease (HFMD) is a prevalent childhood illness caused by coxsackievirus A16 (CVA16).
- Currently, no vaccines or specific treatments exist for CVA16 infections.
Purpose of the Study:
- To identify and characterize CVA16-specific neutralizing monoclonal antibodies (nAbs) with therapeutic potential.
- To elucidate the structural basis of nAb binding to different CVA16 virion forms.
- To evaluate the in vivo efficacy of identified nAbs against CVA16 infection.
Main Methods:
- Identification and characterization of CVA16-specific neutralizing monoclonal antibodies (nAbs).
- Determination of atomic structures of nAbs (18A7, 14B10, NA9D7) in complex with CVA16 mature virions, A-particles, and empty particles.
- Assessment of nAb protection against lethal CVA16 infection in a neonatal mouse model.
Main Results:
- Three nAbs (18A7, 14B10, NA9D7) with therapeutic potential were identified.
- Structural analysis revealed how each Fab fragment binds to the mature CVA16 virion.
- Antibodies 14B10 and NA9D7 conferred 100% protection against lethal CVA16 infection in mice.
- 14B10 and NA9D7 target broad protective epitopes on the mature virion, with NA9D7 potentially overlapping the receptor-binding site.
Conclusions:
- Neutralizing monoclonal antibodies 14B10 and NA9D7 demonstrate significant therapeutic efficacy against CVA16.
- Structural insights guide the development of CVA16 vaccines, suggesting a focus on mature virions.
- These antibodies can serve as tools to identify optimal immunogens for CVA16 vaccine candidates.
Abstract:
Hand, foot, and mouth disease is a common childhood illness primarily caused by coxsackievirus A16 (CVA16), for which there are no current vaccines or treatments. We identify three CVA16-specific neutralizing monoclonal antibodies (nAbs) with therapeutic potential: 18A7, 14B10, and NA9D7. We present atomic structures of these nAbs bound to all three viral particle forms-the mature virion, A-particle, and empty particle-and show that each Fab can simultaneously occupy the mature virion. Additionally, 14B10 or NA9D7 provide 100% protection against lethal CVA16 infection in a neonatal mouse model. 18A7 binds to a non-conserved epitope present in all three particles, whereas 14B10 and NA9D7 recognize broad protective epitopes but only bind the mature virion. NA9D7 targets an immunodominant site, which may overlap the receptor-binding site. These findings indicate that CVA16 vaccines should be based on mature virions and that these antibodies could be used to discriminate optimal virion-based immunogens.
