Identification of specific neutralizing antibodies for highly pathogenic avian influenza H5 2.3.4.4b clades to facilitate vaccine design and therapeutics.

IF 8.4 2区 医学 Q1 IMMUNOLOGY Emerging Microbes & Infections Pub Date : 2024-12-01 Epub Date: 2024-01-22 DOI:10.1080/22221751.2024.2302106
Bao Tuan Duong, Seon Ju Yeo, Hyun Park
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Abstract

The 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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鉴定高致病性禽流感 H5 2.3.4.4b 支系的特异性中和抗体,以促进疫苗设计和治疗。
高致病性禽流感 H5 2.3.4.4 和 2.3.2.1c 亚支系具有不同的抗原特性,是造成大多数人类感染的原因。因此,必须了解抗体抑制这些亚支系病毒的过程,以开发有效的疗法和疫苗,防止它们逃脱中和抗体的作用。在此,我们报告了针对 H5 2.3.4.4b 亚种血凝素(HA)的两种特异性单克隆抗体(mAbs)的表位及其中和能力。结果表明,这两种 mAbs 在 MDCK 细胞和小鼠模型中对 H5 2.3.4.4b 支系病毒挑战提供了特异性保护。通过表位识别和对接研究,我们发现这些新位点(位于HA受体结合位点的130环(S136,T143)和190螺旋(N199,N205)附近,有助于中和mAbs的结合亲和力,以及互补性决定区的六个残基)可以作为靶点,产生具有更强交叉中和能力的抗体。这也有助于了解 H5 2.3.4.4b、h 和 2.3.2.1c 亚支系之间不同的逃逸突变。这些结果提供了具体信息,有助于未来针对这两个亚支系病毒设计疫苗和疗法,因为这两个亚支系病毒都是优势病毒,对人类构成严重威胁。
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来源期刊
Emerging Microbes & Infections
Emerging Microbes & Infections IMMUNOLOGY-MICROBIOLOGY
CiteScore
26.20
自引率
2.30%
发文量
276
审稿时长
20 weeks
期刊介绍: Emerging Microbes & Infections is a peer-reviewed, open-access journal dedicated to publishing research at the intersection of emerging immunology and microbiology viruses. The journal's mission is to share information on microbes and infections, particularly those gaining significance in both biological and clinical realms due to increased pathogenic frequency. Emerging Microbes & Infections is committed to bridging the scientific gap between developed and developing countries. This journal addresses topics of critical biological and clinical importance, including but not limited to: - Epidemic surveillance - Clinical manifestations - Diagnosis and management - Cellular and molecular pathogenesis - Innate and acquired immune responses between emerging microbes and their hosts - Drug discovery - Vaccine development research Emerging Microbes & Infections invites submissions of original research articles, review articles, letters, and commentaries, fostering a platform for the dissemination of impactful research in the field.
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