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基于传染性支气管炎病毒刺突蛋白共有核苷酸序列的DNA疫苗的设计与特性分析

Design and Characterization of a DNA Vaccine Based on Spike with Consensus Nucleotide Sequence against Infectious Bronchitis Virus.

作者信息

Zuo Lei, Yan Wenjun, Song Zhou, Li Hao, Xie Xin, Gu Kui, Ma Peng, Tian Yiming, Zhou Changyu, Zhao Yu, Yang Xin, Wang Hongning

机构信息

Key Laboratory of Bio-Resource and Eco-Environment of Ministry of Education, Animal Disease Prevention and Food Safety Key Laboratory of Sichuan Province, College of Life Sciences, Sichuan University, Chengdu 610064, China.

出版信息

Vaccines (Basel). 2021 Jan 14;9(1):50. doi: 10.3390/vaccines9010050.

Abstract

Avian coronavirus infectious bronchitis virus (IBV) causes severe economic losses in the poultry industry, but its control is hampered by the continuous emergence of new genotypes and the lack of cross-protection among different IBV genotypes. We designed a new immunogen based on a spike with the consensus nucleotide sequence (S_con) that may overcome the extraordinary genetic diversity of IBV. S_con was cloned into a pVAX1 vector to form a new IBV DNA vaccine, pV-S_con. pV-S_con could be correctly expressed in HD11 cells with corresponding post-translational modification, and induced a neutralizing antibody response to the Vero-cell-adapted IBV strain Beaudette (p65) in mice. To further evaluate its immunogenicity, specific-pathogen-free (SPF) chickens were immunized with the pV-S_con plasmid and compared with the control pVAX1 vector and the H120 vaccine. Detection of IBV-specific antibodies and cell cytokines (IL-4 and IFN-γ) indicated that vaccination with pV-S_con efficiently induced both humoral and cellular immune responses. After challenge with the heterologous strain M41, virus shedding and virus loading in tissues was significantly reduced both by pV-S_con and its homologous vaccine H120. Thus, pV-S_con is a promising vaccine candidate for IBV, and the consensus approach is an appealing method for vaccine design in viruses with high variability.

摘要

禽冠状病毒传染性支气管炎病毒(IBV)给家禽业造成了严重的经济损失,但其防控因新基因型的不断出现以及不同IBV基因型之间缺乏交叉保护而受到阻碍。我们基于具有共有核苷酸序列(S_con)的刺突蛋白设计了一种新的免疫原,该免疫原可能克服IBV的高度遗传多样性。将S_con克隆到pVAX1载体中,形成一种新的IBV DNA疫苗pV-S_con。pV-S_con能够在HD11细胞中正确表达,并进行相应的翻译后修饰,且能在小鼠体内诱导针对Vero细胞适应株Beaudette(p65)的中和抗体反应。为进一步评估其免疫原性,用pV-S_con质粒免疫无特定病原体(SPF)鸡,并与对照pVAX1载体和H120疫苗进行比较。对IBV特异性抗体和细胞因子(IL-4和IFN-γ)的检测表明,用pV-S_con疫苗接种能有效诱导体液免疫和细胞免疫反应。在用异源毒株M41攻毒后,pV-S_con及其同源疫苗H120均显著降低了组织中的病毒脱落和病毒载量。因此,pV-S_con是一种有前景的IBV疫苗候选物,共有序列方法是一种针对高变异性病毒进行疫苗设计的有吸引力的方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/54f7/7830736/71bfe8ada999/vaccines-09-00050-g001.jpg

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