Identification of an immunogenic epitope and protective antibody against the furin cleavage site of SARS-CoV-2.
Identification of an immunogenic epitope and protective antibody against the furin cleavage site of SARS-CoV-2.
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DOI：
10.1016/j.ebiom.2022.104401
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发表时间：
2023-01
期刊：
影响因子：
11.1
通讯作者：
Cheng, Genhong
中科院分区：
文献类型：
--
作者：
Li, Lili;Gao, Meiling;Li, Jie;Xie, Xuping;Zhao, Hui;Wang, Yanan;Xu, Xin;Zu, Shulong;Chen, Chunfeng;Wan, Dingyi;Duan, Jing;Wang, Jingfeng;Aliyari, Saba R.;Gold, Sarah;Zhang, Jicai;Qin, Cheng-Feng;Shi, Pei-Yong;Yang, Heng;Cheng, Genhong
严重急性呼吸综合征冠状病毒2型（SARS-CoV-2）是2019年全球冠状病毒病（COVID-19）大流行的病原体，在刺突（S）蛋白中包含独特的四个氨基酸（aa）“PRRA”插入，该插入产生跨膜蛋白酶丝氨酸2（TMPRSS 2）/弗林蛋白酶切割位点并增强病毒感染性。需要对SARS-CoV-2弗林蛋白酶切割位点的免疫原性表位和保护性抗体进行更多的研究。结合计算和实验方法，我们鉴定并表征了与弗林蛋白酶切割位点重叠的免疫原性表位，其检测COVID-19患者中的抗体并在免疫小鼠中激发强烈的抗体应答。我们还从COVID-19患者外周血单核细胞中鉴定出一种高亲和力单克隆抗体;该抗体直接结合弗林蛋白酶切割位点，并在小鼠模型中保护免受SARS-CoV-2感染。SARS-CoV-2的S蛋白中“PRRA”氨基酸的存在不仅产生了弗林蛋白酶切割位点，而且还产生了免疫原性表位，其在COVID-19患者中激发抗体应答。针对该表位的抗体可保护小鼠免受SARS-CoV-2感染。我们已经鉴定的免疫原性表位和保护性抗体可能会增强我们应对COVID-19疫情的策略。的（82102371、91542201、81925025、82073181和81802870），（2021-I2 M-1-047和2022-I2 M-2-004），非营利中央研究所基金（2020-PT 310 -006，2019 XK 310002和2018 TX 31001），中国项目（2020 YFC 0841700），（NIH）基金资助AI 158154，（UCLA）AI和慈善跋涉，以及DGSOM BSRC COVID-19奖励计划。H.Y.公司由（BK 20211554和BE 2022728）支持。
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the global coronavirus disease 2019 (COVID-19) pandemic, contains a unique, four amino acid (aa) “PRRA” insertion in the spike (S) protein that creates a transmembrane protease serine 2 (TMPRSS2)/furin cleavage site and enhances viral infectivity. More research into immunogenic epitopes and protective antibodies against this SARS-CoV-2 furin cleavage site is needed. Combining computational and experimental methods, we identified and characterized an immunogenic epitope overlapping the furin cleavage site that detects antibodies in COVID-19 patients and elicits strong antibody responses in immunized mice. We also identified a high-affinity monoclonal antibody from COVID-19 patient peripheral blood mononuclear cells; the antibody directly binds the furin cleavage site and protects against SARS-CoV-2 infection in a mouse model. The presence of “PRRA” amino acids in the S protein of SARS-CoV-2 not only creates a furin cleavage site but also generates an immunogenic epitope that elicits an antibody response in COVID-19 patients. An antibody against this epitope protected against SARS-CoV-2 infection in mice. The immunogenic epitope and protective antibody we have identified may augment our strategy in handling COVID-19 epidemic. The (82102371, 91542201, 81925025, 82073181, and 81802870), the (2021-I2M-1-047 and 2022-I2M-2-004), the Non-profit Central Research Institute Fund of the (2020-PT310-006, 2019XK310002, and 2018TX31001), the Project of China (2020YFC0841700), (NIH) funds grant AI158154, (UCLA) AI and Charity Treks, and DGSOM BSCRC COVID-19 Award Program. H.Y. is supported by (BK20211554 andBE2022728).
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