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Updated: Aug 20, 2025
Use of Viral Entry Assays and Molecular Docking Analysis for the Identification of Antiviral Candidates against Coxsackievirus A16
Published on: July 15, 2019
Non-neutralizing monoclonal antibody targeting VP2 EF loop of Coxsackievirus A16 can protect mice from lethal attack
Ruixiao Du1, Chaoqiang An2, Xin Yao1
1NHC Key Laboratory of Research on Quality and Standardization of Biotech Products; NMPA Key Laboratory for Quality Research and Evaluation of Biological Products, National Institutes for Food and Drug Control, Beijing, People's Republic of China.
Abstract:
Coxsackievirus A16 (CA16), a main causative agent of hand, foot, and mouth disease (HFMD), has become a serious public health concern in the Asia-Pacific region. Here, we generated an anti-CA16 monoclonal antibody, DMA2017, derived from an epidemic strain CA16. Surprisingly, although DMA2017 could not neutralize the original and circulating CA16 strains in vitro, the passive transfer of DMA2017 (10 μg/g) could protect suckling mice from a lethal challenge with CA16 in vivo. Then, we confirmed the protective effect of DMA2017 relies on the Fc-dependent effector functions, such as antibody-dependent cellular cytotoxicity (ADCC). The linear epitope of DMA2017 was mapped by phage display technique to a conserved patch spanning residues 143-148 (NSHPPY) of the VP2 EF-loop of CA16. DMA2017 could inhibit the binding of the antibodies present in the sera of naturally infected children to CA16, indicating that the epitope of DMA2017 is immunodominant for CA16. Our results confirm, for the first time, that a potential preventive and therapeutic effect could be mediated by a non-neutralizing antibody elicited against CA16. These findings bring a hitherto understudied protective role of non-neutralizing antibodies during viral infections into the spotlight and provide a new perspective on the design and evaluation of CA16 vaccines.
Insights
A new antibody, DMA2017, protects against Coxsackievirus A16 (CA16) infection in mice, even without direct neutralization. This highlights the protective role of non-neutralizing antibodies against hand, foot, and mouth disease (HFMD).
Area of Science:
- Virology
- Immunology
- Public Health
Background:
- Coxsackievirus A16 (CA16) is a primary cause of hand, foot, and mouth disease (HFMD), posing a significant public health challenge, particularly in the Asia-Pacific region.
- Current therapeutic strategies for CA16 infections are limited, necessitating the exploration of novel approaches.
Purpose of the Study:
- To generate and characterize a monoclonal antibody against CA16.
- To investigate the protective mechanisms of a non-neutralizing anti-CA16 antibody, DMA2017.
- To explore the potential of non-neutralizing antibodies in preventing and treating CA16 infections.
Main Methods:
- Generation of a monoclonal antibody (DMA2017) against an epidemic CA16 strain.
- In vitro neutralization assays and in vivo passive transfer studies in suckling mice.
- Epitope mapping using phage display and assessment of Fc-dependent effector functions like antibody-dependent cellular cytotoxicity (ADCC).
Main Results:
- DMA2017 demonstrated in vivo protection against lethal CA16 challenge in mice despite lacking in vitro neutralizing activity.
- The protective effect was attributed to Fc-dependent mechanisms, including ADCC.
- The antibody's epitope (NSHPPY, residues 143-148) on the VP2 EF-loop was identified as immunodominant, blocking antibody binding in naturally infected individuals.
Conclusions:
- Non-neutralizing antibodies, like DMA2017, can confer protection against CA16 infection through Fc-mediated effector functions.
- This study underscores the underappreciated role of non-neutralizing antibodies in viral immunity.
- Findings offer new insights for designing effective CA16 vaccines and therapeutics.
