Generation of Chicken IgY against SARS-COV-2 Spike Protein and Epitope Mapping.

Generation of Chicken IgY against SARS-COV-2 Spike Protein and Epitope Mapping.
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DOI:
10.1155/2020/9465398
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发表时间:
2020
影响因子:
4.1
通讯作者:
Wang W
Wang W
中科院分区:
医学3区
文献类型:
--
作者:
Lu Y;Wang Y;Zhang Z;Huang J;Yao M;Huang G;Ge Y;Zhang P;Huang H;Wang Y;Li H;Wang W

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新的十年始于由严重急性呼吸系统综合征冠状病毒2型(SARS-CoV-2)引起的COVID-19全球大流行,引发了全球健康危机和经济衰退。科学家和临床医生一直在争分夺秒地寻找COVID-19的疗法。重新使用已批准的药物,开发疫苗和采用被动免疫是对抗COVID-19的三种主要治疗方法。鸡Y型免疫球蛋白(IgY)具有亲和力高、免疫不良反应小、易于鼻内局部给药等优点,有望成为抗呼吸道感染的中和抗体。本研究以SARS-CoV-2的S蛋白为抗原,制备了抗S蛋白的鸡源抗体,并从鸡蛋黄中提取了IgY(简称IgY-S)。IgY-S对SARS-CoV-2S具有较强的免疫反应性,通过抗原表位定位,我们发现了SARS-CoV-2S中IgY-S的5个线性抗原表位,其中2个与SARS-CoV-2S有交叉反应。值得注意的是,表位SIIAYTMSL,鉴定的表位之一,部分重叠在SARS-CoV-2 S中的S1/S2切割区域,并且在三维结构中位于S三聚体的表面上,靠近S1/S2切割位点。因此,在该位置的抗体结合可以物理地阻断蛋白水解酶接近S1/S2切割位点,从而阻碍S1/S2蛋白水解切割,这对随后的病毒-细胞膜融合和病毒细胞进入至关重要。因此,利用IgY-S或表位SIIAYTMS特异性IgY作为中和抗体预防或治疗SARS-CoV-2感染的可行性值得探讨。
This new decade has started with a global pandemic of COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), precipitating a worldwide health crisis and economic downturn. Scientists and clinicians have been racing against time to find therapies for COVID-19. Repurposing approved drugs, developing vaccines and employing passive immunization are three major therapeutic approaches to fighting COVID-19. Chicken immunoglobulin Y (IgY) has the potential to be used as neutralizing antibody against respiratory infections, and its advantages include high avidity, low risk of adverse immune responses, and easy local delivery by intranasal administration. In this study, we raised antibody against the spike (S) protein of SARS-CoV-2 in chickens and extracted IgY (called IgY-S) from egg yolk. IgY-S exhibited high immunoreactivity against SARS-CoV-2 S, and by epitope mapping, we found five linear epitopes of IgY-S in SARS-CoV-2 S, two of which are cross-reactive with SARS-CoV S. Notably, epitope SIIAYTMSL, one of the identified epitopes, partially overlaps the S1/S2 cleavage region in SARS-CoV-2 S and is located on the surface of S trimer in 3D structure, close to the S1/S2 cleavage site. Thus, antibody binding at this location could physically block the access of proteolytic enzymes to S1/S2 cleavage site and thereby impede S1/S2 proteolytic cleavage, which is crucial to subsequent virus-cell membrane fusion and viral cell entry. Therefore, the feasibility of using IgY-S or epitope SIIAYTMS-specific IgY as neutralizing antibody for preventing or treating SARS-CoV-2 infection is worth exploring.
Chadox1 NCOV-19疫苗可防止恒河猕猴中的SARS-COV-2肺炎。
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期刊: Nature
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影响因子: 28.3
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发表时间: 2020-02-15
期刊: LANCET
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发表时间: 2007-05-15
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DOI: 10.3791/3084
发表时间: 2011-05-01
期刊: Journal of visualized experiments : JoVE
影响因子: --
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