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痘苗病毒天坛株表达的SARS-CoV刺突蛋白:分泌型Sq蛋白在小鼠中诱导产生强效中和抗体。

SARS-CoV spike proteins expressed by the vaccinia virus Tiantan strain: secreted sq protein induces robust neutralization antibody in mice.

作者信息

Yan Kexia, Tan Wenjie, Wang Huijuan, Wang Yue, Zhang Xiangmin, Li Yan, Ruan Li

机构信息

National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, People's Republic of China.

出版信息

Viral Immunol. 2009 Feb;22(1):57-66. doi: 10.1089/vim.2008.0064.

Abstract

The spike (S) glycoprotein of severe acute respiratory syndrome coronavirus (SARS-CoV) is a major target in the development of diagnostic assays and vaccines, but its antigenic and immunogenic properties remain unclear. Seven SARS-CoV spike proteins (S, SQ, S1, RBD, S2, S2Q, and CX) were generated using the modified vaccinia virus (Tiantan strain) as a vector, and their antigenicity and immunogenicity were evaluated. The secreted SQ protein in which the transmembrane domain was deleted, as well as the full-length spike protein, showed the most potential to induce the production of neutralizing antibody (nAb) in mice. S1 and RBD proteins initialized significantly lower levels of nAb production. In addition, the S proteins were recognized specifically by the sera of convalescent patients with SARS, and that of mice immunized with inactivated SARS-CoV, but did not react with anti-sera of HCoV-OC43 or HCoV-229E, or sera from healthy donors (although RBD showed a false-positive in 1 of 55 control samples of human sera). Our results demonstrate that SQ protein may be an effective vaccine candidate and a convenient and safe diagnostic antigen for SARS-CoV.

摘要

严重急性呼吸综合征冠状病毒(SARS-CoV)的刺突(S)糖蛋白是诊断检测和疫苗研发的主要靶点,但其抗原性和免疫原性仍不清楚。使用改良痘苗病毒(天坛株)作为载体产生了七种SARS-CoV刺突蛋白(S、SQ、S1、RBD、S2、S2Q和CX),并对其抗原性和免疫原性进行了评估。缺失跨膜结构域的分泌型SQ蛋白以及全长刺突蛋白在诱导小鼠产生中和抗体(nAb)方面显示出最大潜力。S1和RBD蛋白诱导产生的nAb水平显著较低。此外,S蛋白能被SARS康复患者血清以及用灭活SARS-CoV免疫的小鼠血清特异性识别,但不与HCoV-OC43或HCoV-229E的抗血清或健康供体血清发生反应(尽管RBD在55份人类血清对照样本中有1份出现假阳性)。我们的结果表明,SQ蛋白可能是一种有效的SARS-CoV疫苗候选物以及方便、安全的诊断抗原。

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