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科学家设计出通用型冠状病毒疫苗
2020-06-29 17:43

中国科学院微生物研究所高福等研究人员合作设计了靶向COVID-19、MERS和SARS的通用型冠状病毒疫苗。这一研究成果于2020年6月28日在线发表在《细胞》上。

研究人员表示,目前迫切需要疫苗来控制大流行的COVID-19和由冠状病毒(CoV)感染引起的MERS/SARS。CoV刺突受体结合结构域(RBD)是潜在的疫苗靶标,但是由于有限的免疫原性而无法实现。
 
研究人员报道了克服这一限制的MERS-CoV RBD的二聚体形式。与常规单体形式相比,RBD二聚体显著提高了中和抗体(NAb)的效价,并保护了小鼠免受MERS-CoV感染。晶体结构显示RBD二聚体完全暴露了双重受体结合基序,这是NAbs的主要靶标。结构指导的设计进一步产生了稳定的RBD二聚体形式,即串联重复单链(RBD-sc-二聚体),从而保留了疫苗效力。
 
研究人员推广了这种策略来设计针对COVID-19和SARS的疫苗,从而将NAb滴度提高了10-100倍。RBD-sc-二聚体在中试规模生产中获得了高产量,为进一步的临床开发提供了支持。这一免疫原设计框架可以普遍应用于其他β-CoV疫苗,以应对新出现的威胁。
 
附:英文原文

Title: A universal design of betacoronavirus vaccines against COVID-19, MERS and SARS

Author: Lianpan Dai, Tianyi Zheng, Kun Xu, Yuxuan Han, Lili Xu, Enqi Huang, Yaling An, Yingjie Cheng, Shihua Li, Mei Liu, Mi Yang, Yan Li, Huijun Cheng, Yuan Yuan, Wei Zhang, Changwen Ke, Gary Wong, Jianxun Qi, Chuan Qin, Jinghua Yan, George F. Gao

Issue&Volume: 2020-06-28

Abstract: Vaccines are urgently needed to control the ongoing pandemic COVID-19 and previously-emerging MERS/SARS caused by coronavirus (CoV) infections. The CoV spike receptor-binding domain (RBD) is an attractive vaccine target but is undermined by limited immunogenicity. We describe a dimeric form of MERS-CoV RBD that overcomes this limitation. The RBD-dimer significantly increased neutralizing antibody (NAb) titers compared to conventional monomeric form and protected mice against MERS-CoV infection. Crystal structure showed RBD-dimer fully exposed dual receptor-binding motifs, the major target for NAbs. Structure-guided design further yielded a stable version of RBD-dimer as a tandem repeat single-chain (RBD-sc-dimer) which retained the vaccine potency. We generalized this strategy to design vaccines against COVID-19 and SARS, achieving 10-100-fold enhancement of NAb titers. RBD-sc-dimers in pilot scale production yielded high yields, supporting their scalability for further clinical development. The framework of immunogen design can be universally applied to other beta-CoV vaccines to counter emerging threats.

DOI: 10.1016/j.cell.2020.06.035

Source: https://www.cell.com/cell/fulltext/S0092-8674(20)30812-6

Cell:《细胞》,创刊于1974年。隶属于细胞出版社,最新IF:36.216
官方网址:https://www.cell.com/
投稿链接:https://www.editorialmanager.com/cell/default.aspx

本期文章:《细胞》:Online/在线发表

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