Computationally designed haemagglutinin with nanocage plug-and-display elicits pan-H5 influenza vaccine responses.

IF 7.5 2区医学 Q1 IMMUNOLOGY

Emerging Microbes & Infections Pub Date : 2025-12-01 Epub Date: 2025-07-11 DOI:10.1080/22221751.2025.2511132

Chloe Qingzhou Huang, Rory A Hills, George W Carnell, Sneha Vishwanath, Ernest T Aguinam, Andrew C Y Chan, Phil Palmer, Laura O'Reilly, Paul Tonks, Nigel Temperton, Simon D W Frost, Laurence S Tiley, Mark R Howarth, Jonathan L Heeney

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引用次数: 0

Abstract

The increasing spread of highly pathogenic avian influenza (HPAI) A/H5 viruses poses a pandemic threat. Circulating clade 2.3.4.4b viruses have demonstrated rapid transcontinental dissemination, extensive reassortment, epizootic spread and potential sustained mammal-to-mammal transmission, signifying a heightened risk of becoming a human pathogen of high consequence. A broadly protective, future-proof vaccine against multiple clades of H5 influenza is urgently needed for pandemic preparedness. Here, we combine two novel vaccine technologies to generate a Digitally Immune Optimised and Selected H5 antigen (DIOSvax-H5_inter) displayed multivalently on the mi3 nanocage using the SpyTag003/SpyCatcher003 conjugation system. Mice immunized with DIOSvax-H5_inter Homotypic Nanocages at low doses demonstrate potent, cross-clade neutralizing antibody and T cell responses against diverse H5 strains. DIOSvax-H5_inter Homotypic Nanocages provide a scalable vaccine candidate with the potential for pan-H5 protection against drifted or newly emergent H5 strains. This World Health Organization preferred characteristic is essential for prospective strategic stockpiling in the pre-pandemic phase.

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计算设计的血凝素与纳米笼plug-and-display引发泛h5流感疫苗反应。

高致病性禽流感（HPAI） A/H5病毒的日益传播构成了大流行威胁。流行的进化支2.3.4.4b病毒已显示出快速的跨大陆传播、广泛的重组、动物流行病传播和潜在的持续哺乳动物间传播，这表明成为具有高度后果的人类病原体的风险增加。目前迫切需要一种具有广泛保护作用的、面向未来的疫苗，以防范H5流感的多个分支。在这里，我们结合了两种新型疫苗技术，使用SpyTag003/SpyCatcher003偶联系统，产生了一种数字免疫优化和选择的H5抗原（DIOSvax-H5inter）在mi3纳米容器上多价显示。用低剂量DIOSvax-H5inter Homotypic Nanocages免疫小鼠，对多种H5毒株表现出有效的跨进化中和抗体和T细胞反应。DIOSvax-H5inter Homotypic纳米笼提供了一种可扩展的候选疫苗，具有针对漂移或新出现的H5毒株的泛H5保护潜力。这一世界卫生组织喜欢的特性对于大流行前阶段的前瞻性战略储备至关重要。试验注册：ClinicalTrials.gov标识符：NCT06145178。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

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.