Lipid nanoparticles-mRNA based on the consensus sequences of avian coronavirus S1 and N genes protect animals against multiple viral infections.

IF 12.6 1区 生物学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY
Hongtao Xiao, Wanyan Wu, Siyao Yu, Jiayang Chen, Lijin Lai, Jinlian Ren, Xiaotong Yan, Qiuyan Lin, Libin Chen, Tao Ren
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Abstract

Lipid nanoparticles-mRNA play important roles in SARS-CoV-2 infection control. Avian coronavirus infectious bronchitis virus (IBV) comprises eight genotypes with a lack of cross-protection, causing severe economic losses to the poultry industry. Using immunoinformatics methods, five consensus sequence antigens against prevalent IBV strains were designed. Four monovalent lipid nanoparticles-mRNA (GI-19, GI-13, GI-7, GVI-1) and one quadrivalent lipid nanoparticles-mRNA were constructed to develop a broad-spectrum IBV vaccine. The safety and biodistribution of the lipid nanoparticles-mRNA were evaluated in SPF chickens and confirmed that it induced a strong and durable immune response. The lipid nanoparticles-mRNA efficacy in SPF chickens was verified in infection assays with four genotypes of IBV strains, the results showed that immunization with a 10 µg dose provided complete protection for the chickens, while immunization with a 5 µg dose reduced disease severity, organ damage, and mortality, and inhibited viral replication and shedding. Our results indicate that these Lipid nanoparticles-mRNA are immunogenic and protective in preclinical animal models. These data can provide a basis for IBV prevention and control and the development of mRNA vaccines against other prevalent viruses.

基于禽冠状病毒S1和N基因共识序列的脂质纳米颗粒- mrna保护动物免受多种病毒感染。
脂质纳米粒mrna在SARS-CoV-2感染控制中发挥重要作用。禽冠状病毒传染性支气管炎病毒(IBV)包括8种缺乏交叉保护的基因型,给家禽业造成严重的经济损失。采用免疫信息学方法,设计了5种针对IBV流行株的一致序列抗原。构建了4个单价脂质纳米粒- mrna (GI-19、GI-13、GI-7、GVI-1)和1个四价脂质纳米粒- mrna,用于开发广谱IBV疫苗。脂质纳米颗粒mrna在SPF鸡体内的安全性和生物分布进行了评价,并证实其诱导了强烈而持久的免疫反应。脂质纳米颗粒- mrna对SPF鸡的感染效果通过四种基因型IBV菌株的感染试验得到验证,结果表明,10µg免疫剂量对鸡有完全的保护作用,而5µg免疫剂量可降低疾病严重程度、器官损伤和死亡率,并抑制病毒的复制和脱落。我们的研究结果表明,这些脂质纳米颗粒- mrna在临床前动物模型中具有免疫原性和保护性。这些数据可为IBV的预防和控制以及针对其他流行病毒的mRNA疫苗的开发提供依据。
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来源期刊
Journal of Nanobiotechnology
Journal of Nanobiotechnology BIOTECHNOLOGY & APPLIED MICROBIOLOGY-NANOSCIENCE & NANOTECHNOLOGY
CiteScore
13.90
自引率
4.90%
发文量
493
审稿时长
16 weeks
期刊介绍: Journal of Nanobiotechnology is an open access peer-reviewed journal communicating scientific and technological advances in the fields of medicine and biology, with an emphasis in their interface with nanoscale sciences. The journal provides biomedical scientists and the international biotechnology business community with the latest developments in the growing field of Nanobiotechnology.
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