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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Main Authors: Bao Tuan Duong, Seon Ju Yeo, Hyun Park
Format: Article
Language:English
Published: Taylor & Francis Group 2024-12-01
Series:Emerging Microbes and Infections
Subjects:
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.
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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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