Zhao Liang, Wei Xue-Feng, Xu Kun, Zhao Zhao, Chen Guo, Wang Hou-Peng, Zhu Bin
College of Animal Science and Technology, Northwest A&F University College of Animal Science and Technology, Yangling, China.
State Key Laboratory of Freshwater Ecology and Biotechnology, Hongshan Laboratory, Institute of Hydrobiology, Innovation Academy for Seed Design, Chinese Academy of Sciences, Wuhan, China.
J Virol. 2025 Jan 31;99(1):e0149724. doi: 10.1128/jvi.01497-24. Epub 2024 Dec 23.
The occurrence of viral diseases poses a huge threat and impact on human public health safety and the development of the animal and fishery industry. Here, a strain of single-chain antibody fragment, scFv-1, was isolated from the phage antibody display library construct by immunizing New Zealand white rabbits with rhabdovirus. analysis showed that the single-chain antibody could inhibit the infection of the virus in multiple pathways, including adsorption, fusion, and release. analysis revealed scFv-1 had a preventive and protective effect against the infection of virus. In addition, we describe that transposon-based transport of neutralizing genes allows for long-term, continuous expression, avoiding the need for lifelong, repeated passive immunization for treatment. In sum, high-throughput screening of neutralization genes based on phage display technology and transposon vector-based gene transfer provides effective methods for treating and preventing diseases and avoiding repetitive passive immunotherapy. This study also provides a reference for the prevention and treatment of unknown pathogens.IMPORTANCELivestock and fisheries play an important role in economic development and food security. The frequent outbreaks of viral diseases have caused great losses to the livestock industry, while the increase in drug resistance caused by the use of antibiotics as well as the potential risks to human health have raised serious concerns. Here, we constructed a phage display antibody library by immunizing New Zealand white rabbits with purified rhabdovirus and selected a single-chain antibody, scFv-1, with good neutralizing activity, which was validated and found to be able to block multiple phases of the virus and thus play a neutralizing role. In addition, we describe that transposon-based transport of neutralizing genes allows for long-term, continuous expression, reducing the need for lifelong, repeated passive immunization for treatment. Our work not only provides methods for the prevention and treatment of viral diseases but also provides the body with long-lasting and even permanent protection against repeated passive immunization.
病毒性疾病的发生对人类公共卫生安全以及动物和渔业产业的发展构成了巨大威胁和影响。在此，通过用弹状病毒免疫新西兰白兔，从噬菌体抗体展示文库构建体中分离出了一株单链抗体片段scFv-1。分析表明，该单链抗体可通过多种途径抑制病毒感染，包括吸附、融合和释放。分析显示scFv-1对病毒感染具有预防和保护作用。此外，我们描述了基于转座子的中和基因转运可实现长期、持续表达，避免了治疗中终身重复被动免疫的需要。总之，基于噬菌体展示技术的中和基因高通量筛选和基于转座子载体的基因转移为疾病的治疗和预防以及避免重复被动免疫治疗提供了有效方法。本研究也为未知病原体的防治提供了参考。
重要性
畜牧业和渔业在经济发展和粮食安全中发挥着重要作用。病毒性疾病的频繁爆发给畜牧业造成了巨大损失，而使用抗生素导致的耐药性增加以及对人类健康的潜在风险引发了严重关注。在此，我们通过用纯化的弹状病毒免疫新西兰白兔构建了噬菌体展示抗体文库，并筛选出具有良好中和活性的单链抗体scFv-1，经验证发现其能够阻断病毒的多个阶段，从而发挥中和作用。此外，我们描述了基于转座子的中和基因转运可实现长期、持续表达，减少了治疗中终身重复被动免疫的需要。我们的工作不仅为病毒性疾病的防治提供了方法，还为机体提供了针对重复被动免疫的持久甚至永久保护。
