Identification of specific neutralizing antibodies for highly pathogenic avian influenza H5 2.3.4.4b clades to facilitate vaccine design and therapeutics
ABSTRACTThe highly pathogenic avian influenza H5 2.3.4.4 and 2.3.2.1c subclades have distinct antigenic properties and are responsible for the majority of human infections. Therefore, it is essential to understand the processes by which antibodies inhibit these subclade viruses to develop effective...
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Format: | Article |
Language: | English |
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Taylor & Francis Group
2024-12-01
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Series: | Emerging Microbes and Infections |
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Online Access: | https://www.tandfonline.com/doi/10.1080/22221751.2024.2302106 |
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author | Bao Tuan Duong Seon Ju Yeo Hyun Park |
author_facet | Bao Tuan Duong Seon Ju Yeo Hyun Park |
author_sort | Bao Tuan Duong |
collection | DOAJ |
description | ABSTRACTThe highly pathogenic avian influenza H5 2.3.4.4 and 2.3.2.1c subclades have distinct antigenic properties and are responsible for the majority of human infections. Therefore, it is essential to understand the processes by which antibodies inhibit these subclade viruses to develop effective therapies and vaccines to prevent their escape from neutralizing antibodies. Herein, we report the epitopes of two specific monoclonal antibodies (mAbs) targeting haemagglutinin (HA) of the H5 2.3.4.4b subclade and their neutralizing abilities. The results indicated that the two mAbs provided specific protection against the H5 2.3.4.4b clade viral challenge in MDCK cells and mouse models. Through epitope identification and docking studies, we showed that these novel sites (which are located near the 130-loop (S136, T143) and 190-helix (N199, N205) of HA receptor-binding sites that contribute to the binding affinity of neutralizing mAbs and six residues of the complementarity-determining regions) can be targeted to generate antibodies with enhanced cross-neutralization. This can also help in understanding escape mutations that differ among the H5 2.3.4.4b, h, and 2.3.2.1c subclades. These results provide specific information to facilitate future vaccine design and therapeutics for both subclade viruses, which are dominant and pose a serious threat to humans. |
first_indexed | 2024-03-08T12:10:20Z |
format | Article |
id | doaj.art-101d8fabc4a34f6ea33cb6f63252ebbc |
institution | Directory Open Access Journal |
issn | 2222-1751 |
language | English |
last_indexed | 2024-03-08T12:10:20Z |
publishDate | 2024-12-01 |
publisher | Taylor & Francis Group |
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series | Emerging Microbes and Infections |
spelling | doaj.art-101d8fabc4a34f6ea33cb6f63252ebbc2024-01-22T22:27:51ZengTaylor & Francis GroupEmerging Microbes and Infections2222-17512024-12-0113110.1080/22221751.2024.2302106Identification of specific neutralizing antibodies for highly pathogenic avian influenza H5 2.3.4.4b clades to facilitate vaccine design and therapeuticsBao Tuan Duong0Seon Ju Yeo1Hyun Park2Zoonosis Research Center, Department of Infection Biology, School of Medicine, Wonkwang University, Iksan, KoreaDepartment of Tropical Medicine and Parasitology, Department of Biomedical Sciences, College of Medicine, Seoul National University, Seoul, Republic of KoreaZoonosis Research Center, Department of Infection Biology, School of Medicine, Wonkwang University, Iksan, KoreaABSTRACTThe highly pathogenic avian influenza H5 2.3.4.4 and 2.3.2.1c subclades have distinct antigenic properties and are responsible for the majority of human infections. Therefore, it is essential to understand the processes by which antibodies inhibit these subclade viruses to develop effective therapies and vaccines to prevent their escape from neutralizing antibodies. Herein, we report the epitopes of two specific monoclonal antibodies (mAbs) targeting haemagglutinin (HA) of the H5 2.3.4.4b subclade and their neutralizing abilities. The results indicated that the two mAbs provided specific protection against the H5 2.3.4.4b clade viral challenge in MDCK cells and mouse models. Through epitope identification and docking studies, we showed that these novel sites (which are located near the 130-loop (S136, T143) and 190-helix (N199, N205) of HA receptor-binding sites that contribute to the binding affinity of neutralizing mAbs and six residues of the complementarity-determining regions) can be targeted to generate antibodies with enhanced cross-neutralization. This can also help in understanding escape mutations that differ among the H5 2.3.4.4b, h, and 2.3.2.1c subclades. These results provide specific information to facilitate future vaccine design and therapeutics for both subclade viruses, which are dominant and pose a serious threat to humans.https://www.tandfonline.com/doi/10.1080/22221751.2024.2302106H5n62.3.4.4b Subcladehighly pathogenic avian influenzaepitope mappingprotein-protein dockingcombination therapy |
spellingShingle | Bao Tuan Duong Seon Ju Yeo Hyun Park Identification of specific neutralizing antibodies for highly pathogenic avian influenza H5 2.3.4.4b clades to facilitate vaccine design and therapeutics Emerging Microbes and Infections H5n6 2.3.4.4b Subclade highly pathogenic avian influenza epitope mapping protein-protein docking combination therapy |
title | Identification of specific neutralizing antibodies for highly pathogenic avian influenza H5 2.3.4.4b clades to facilitate vaccine design and therapeutics |
title_full | Identification of specific neutralizing antibodies for highly pathogenic avian influenza H5 2.3.4.4b clades to facilitate vaccine design and therapeutics |
title_fullStr | Identification of specific neutralizing antibodies for highly pathogenic avian influenza H5 2.3.4.4b clades to facilitate vaccine design and therapeutics |
title_full_unstemmed | Identification of specific neutralizing antibodies for highly pathogenic avian influenza H5 2.3.4.4b clades to facilitate vaccine design and therapeutics |
title_short | Identification of specific neutralizing antibodies for highly pathogenic avian influenza H5 2.3.4.4b clades to facilitate vaccine design and therapeutics |
title_sort | identification of specific neutralizing antibodies for highly pathogenic avian influenza h5 2 3 4 4b clades to facilitate vaccine design and therapeutics |
topic | H5n6 2.3.4.4b Subclade highly pathogenic avian influenza epitope mapping protein-protein docking combination therapy |
url | https://www.tandfonline.com/doi/10.1080/22221751.2024.2302106 |
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