Non-neutralizing monoclonal antibody targeting VP2 EF loop of Coxsackievirus A16 can protect mice from lethal attack via Fc-dependent effector mechanism
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 n...
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Taylor & Francis Group
2023-12-01
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| Series: | Emerging Microbes and Infections |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/22221751.2022.2149352 |
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| author | Ruixiao Du Chaoqiang An Xin Yao Yiping Wang Ge Wang Fan Gao Lianlian Bian Yalin Hu Siyuan Liu Qiaohui Zhao Qunying Mao Zhenglun Liang |
| author_facet | Ruixiao Du Chaoqiang An Xin Yao Yiping Wang Ge Wang Fan Gao Lianlian Bian Yalin Hu Siyuan Liu Qiaohui Zhao Qunying Mao Zhenglun Liang |
| author_sort | Ruixiao Du |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-ef1f3e3d564849af80c0ac76b8d2f283 |
| institution | OA Journals |
| issn | 2222-1751 |
| language | English |
| publishDate | 2023-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Emerging Microbes and Infections |
| spelling | doaj-art-ef1f3e3d564849af80c0ac76b8d2f2832025-08-20T01:49:27ZengTaylor & Francis GroupEmerging Microbes and Infections2222-17512023-12-0112110.1080/22221751.2022.2149352Non-neutralizing monoclonal antibody targeting VP2 EF loop of Coxsackievirus A16 can protect mice from lethal attack via Fc-dependent effector mechanismRuixiao Du0Chaoqiang An1Xin Yao2Yiping Wang3Ge Wang4Fan Gao5Lianlian Bian6Yalin Hu7Siyuan Liu8Qiaohui Zhao9Qunying Mao10Zhenglun Liang11NHC 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 ChinaBeijing minhai Biotechnology Co. Ltd, Beijing, People’s Republic of ChinaNHC 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 ChinaNHC 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 ChinaAutobio Diagnostics Co. Ltd, Zhengzhou, People’s Republic of ChinaNHC 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 ChinaNHC 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 ChinaNHC 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 ChinaBeijing minhai Biotechnology Co. Ltd, Beijing, People’s Republic of ChinaAutobio Diagnostics Co. Ltd, Zhengzhou, People’s Republic of ChinaNHC 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 ChinaNHC 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 ChinaCoxsackievirus 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.https://www.tandfonline.com/doi/10.1080/22221751.2022.2149352Coxsackievirus A16non-neutralizing monoclonal antibodyprotective effectepitopeFc-dependent effector functionsantibody-dependent cellular cytotoxicity |
| spellingShingle | Ruixiao Du Chaoqiang An Xin Yao Yiping Wang Ge Wang Fan Gao Lianlian Bian Yalin Hu Siyuan Liu Qiaohui Zhao Qunying Mao Zhenglun Liang Non-neutralizing monoclonal antibody targeting VP2 EF loop of Coxsackievirus A16 can protect mice from lethal attack via Fc-dependent effector mechanism Emerging Microbes and Infections Coxsackievirus A16 non-neutralizing monoclonal antibody protective effect epitope Fc-dependent effector functions antibody-dependent cellular cytotoxicity |
| title | Non-neutralizing monoclonal antibody targeting VP2 EF loop of Coxsackievirus A16 can protect mice from lethal attack via Fc-dependent effector mechanism |
| title_full | Non-neutralizing monoclonal antibody targeting VP2 EF loop of Coxsackievirus A16 can protect mice from lethal attack via Fc-dependent effector mechanism |
| title_fullStr | Non-neutralizing monoclonal antibody targeting VP2 EF loop of Coxsackievirus A16 can protect mice from lethal attack via Fc-dependent effector mechanism |
| title_full_unstemmed | Non-neutralizing monoclonal antibody targeting VP2 EF loop of Coxsackievirus A16 can protect mice from lethal attack via Fc-dependent effector mechanism |
| title_short | Non-neutralizing monoclonal antibody targeting VP2 EF loop of Coxsackievirus A16 can protect mice from lethal attack via Fc-dependent effector mechanism |
| title_sort | non neutralizing monoclonal antibody targeting vp2 ef loop of coxsackievirus a16 can protect mice from lethal attack via fc dependent effector mechanism |
| topic | Coxsackievirus A16 non-neutralizing monoclonal antibody protective effect epitope Fc-dependent effector functions antibody-dependent cellular cytotoxicity |
| url | https://www.tandfonline.com/doi/10.1080/22221751.2022.2149352 |
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