RBD-Fc-based COVID-19 vaccine candidate induces highly potent SARS-CoV-2 neutralizing antibody response.

RBD-Fc-based COVID-19 vaccine candidate induces highly potent SARS-CoV-2 neutralizing antibody response.
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DOI:
10.1038/s41392-020-00402-5
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发表时间:
2020-11-27
影响因子:
39.3
通讯作者:
Jiang S
Jiang S
中科院分区:
医学1区
文献类型:
--
作者:
Liu Z;Xu W;Xia S;Gu C;Wang X;Wang Q;Zhou J;Wu Y;Cai X;Qu D;Ying T;Xie Y;Lu L;Yuan Z;Jiang S

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由严重急性呼吸综合征冠状病毒2型(SARS-CoV-2)引起的2019冠状病毒病(COVID-19)大流行对全球健康和经济构成严重威胁,因此需要开发安全有效的疫苗。SARS-CoV-2刺突蛋白的受体结合域(receptor-binding domain,RBD)负责与血管紧张素转换酶2(angiotensin-converting enzyme 2,ACE 2)受体的结合。它含有多个优势中和表位,是开发COVID-19疫苗的重要抗原。在这里,我们表明,用由SARS-CoV-2 RBD和人IgG的Fc片段组成的候选亚单位疫苗作为免疫增强剂免疫小鼠,引起高滴度的RBD特异性抗体,其对假型和活的SARS-CoV-2感染具有稳健的中和活性。小鼠抗血清也能有效地中和具有几个天然突变的假型SARS-CoV-2的感染,从小鼠抗血清中提取的IgG也能中和假型SARS-CoV和SARS-related coronavirus(SARS-Sr-CoV)。用RBD-Fc免疫人ACE 2转基因小鼠可有效保护小鼠免受SARS-CoV-2攻击。这些结果表明,SARS-CoV-2 RBD-Fc具有良好的潜力,可以进一步开发为有效和广谱的疫苗,以预防当前SARS-CoV-2及其突变体的感染,以及未来新出现的SARS-CoV和重新出现的SARS-CoV。
The pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has posed serious threats to global health and economy, thus calling for the development of safe and effective vaccines. The receptor-binding domain (RBD) in the spike protein of SARS-CoV-2 is responsible for its binding to angiotensin-converting enzyme 2 (ACE2) receptor. It contains multiple dominant neutralizing epitopes and serves as an important antigen for the development of COVID-19 vaccines. Here, we showed that immunization of mice with a candidate subunit vaccine consisting of SARS-CoV-2 RBD and Fc fragment of human IgG, as an immunopotentiator, elicited high titer of RBD-specific antibodies with robust neutralizing activity against both pseudotyped and live SARS-CoV-2 infections. The mouse antisera could also effectively neutralize infection by pseudotyped SARS-CoV-2 with several natural mutations in RBD and the IgG extracted from the mouse antisera could also show neutralization against pseudotyped SARS-CoV and SARS-related coronavirus (SARSr-CoV). Vaccination of human ACE2 transgenic mice with RBD-Fc could effectively protect mice from the SARS-CoV-2 challenge. These results suggest that SARS-CoV-2 RBD-Fc has good potential to be further developed as an effective and broad-spectrum vaccine to prevent infection of the current SARS-CoV-2 and its mutants, as well as future emerging SARSr-CoVs and re-emerging SARS-CoV.
DOI: 10.1038/nrmicro.2016.81
发表时间: 2016-08
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影响因子: --
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