Huang Chloe Qingzhou, Hills Rory A, Carnell George W, Vishwanath Sneha, Aguinam Ernest T, Chan Andrew C Y, Palmer Phil, O'Reilly Laura, Tonks Paul, Temperton Nigel, Frost Simon D W, Tiley Laurence S, Howarth Mark R, Heeney Jonathan L
Laboratory of Viral Zoonotics, Department of Veterinary Medicine, University of Cambridge, Cambridge, UK.
Department of Pharmacology, University of Cambridge, Cambridge, UK.
Emerg Microbes Infect. 2025 Dec;14(1):2511132. doi: 10.1080/22221751.2025.2511132. Epub 2025 Jul 11.
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) displayed multivalently on the mi3 nanocage using the SpyTag003/SpyCatcher003 conjugation system. Mice immunized with DIOSvax-H5 Homotypic Nanocages at low doses demonstrate potent, cross-clade neutralizing antibody and T cell responses against diverse H5 strains. DIOSvax-H5 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.
高致病性禽流感(HPAI)A/H5病毒的不断传播构成了大流行威胁。正在传播的2.3.4.4b分支病毒已显示出跨大陆的快速传播、广泛的重配、动物流行病传播以及潜在的持续哺乳动物间传播,这意味着其成为具有高度影响的人类病原体的风险增加。为防范大流行,迫切需要一种针对多种H5流感分支的具有广泛保护作用且面向未来的疫苗。在此,我们结合两种新型疫苗技术,利用SpyTag003/SpyCatcher003共轭系统,生成一种在mi3纳米笼上多价展示的数字免疫优化与筛选的H5抗原(DIOSvax-H5)。用低剂量的DIOSvax-H5同型纳米笼免疫的小鼠表现出针对多种H5毒株的强效、跨分支中和抗体及T细胞反应。DIOSvax-H5同型纳米笼提供了一种可扩展的疫苗候选物,具有针对发生抗原漂移或新出现的H5毒株提供泛H5保护的潜力。世界卫生组织所青睐的这一特性对于大流行前阶段的前瞻性战略储备至关重要。