Antibodies against trimeric S glycoprotein protect hamsters against SARS-CoV challenge despite their capacity to mediate FcgammaRII-dependent entry into B cells in vitro.
Antibodies against trimeric S glycoprotein protect hamsters against SARS-CoV challenge despite their capacity to mediate FcgammaRII-dependent entry into B cells in vitro.
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DOI：
10.1016/j.vaccine.2006.08.011
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发表时间：
2007-01-08
期刊：
影响因子：
5.5
通讯作者：
Altmeyer R
中科院分区：
文献类型：
--
作者：
Kam YW;Kien F;Roberts A;Cheung YC;Lamirande EW;Vogel L;Chu SL;Tse J;Guarner J;Zaki SR;Subbarao K;Peiris M;Nal B;Altmeyer R
疫苗诱导的抗体可以预防或在猫传染性腹膜炎病毒的情况下加重冠状病毒的感染。我们研究了严重急性呼吸综合征冠状病毒（SARS-CoV）的重组天然全长S蛋白三聚体（triSpike）是否能够在动物中引起中和和保护性免疫应答，并分析了抗S抗体介导体外病毒进入的抗体依赖性增强（ADE）和体内复制增强的能力。SARS-CoV特异性血清和粘膜免疫球蛋白在免疫动物中很容易检测到。血清IgG阻断了S蛋白与ACE 2受体的结合，并在体外中和了SARS-CoV感染。SARS冠状病毒进入人B细胞系的方式依赖于Fcγ RII而不依赖于ACE 2，表明病毒进入细胞的ADE是SARS冠状病毒进入细胞的一种新机制。接种疫苗的动物没有表现出增强的肺部病理或肝炎的迹象，并且在用SARS-CoV攻击后，肺部的病毒载量检测不到或大大减少。总之，我们的研究结果表明，重组三聚体S蛋白能够在体内引起有效的保护性免疫应答，并值得关注的安全性评价的人疫苗对SARS冠状病毒。
Vaccine-induced antibodies can prevent or, in the case of feline infectious peritonitis virus, aggravate infections by coronaviruses. We investigated whether a recombinant native full-length S-protein trimer (triSpike) of severe acute respiratory syndrome coronavirus (SARS-CoV) was able to elicit a neutralizing and protective immune response in animals and analyzed the capacity of anti-S antibodies to mediate antibody-dependent enhancement (ADE) of virus entry in vitro and enhancement of replication in vivo. SARS-CoV-specific serum and mucosal immunoglobulins were readily detected in immunized animals. Serum IgG blocked binding of the S-protein to the ACE2 receptor and neutralized SARS-CoV infection in vitro. Entry into human B cell lines occurred in a FcγRII-dependent and ACE2-independent fashion indicating that ADE of virus entry is a novel cell entry mechanism of SARS-CoV. Vaccinated animals showed no signs of enhanced lung pathology or hepatitis and viral load was undetectable or greatly reduced in lungs following challenge with SARS-CoV. Altogether our results indicate that a recombinant trimeric S protein was able to elicit an efficacious protective immune response in vivo and warrant concern in the safety evaluation of a human vaccine against SARS-CoV.
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影响因子：
64.8
作者：
Li W;Moore MJ;Vasilieva N;Sui J;Wong SK;Berne MA;Somasundaran M;Sullivan JL;Luzuriaga K;Greenough TC;Choe H;Farzan M
通讯作者：
Farzan M
影响因子：
3.7
作者：
Gómez, N;Carrillo, C;Escribano, JM
通讯作者：
Escribano, JM
影响因子：
5
作者：
Daeron, M
通讯作者：
Daeron, M
SARS-COV峰值蛋白的受体结合结构域可诱导高度有效的中和抗体：对开发亚基疫苗的影响。
DOI：
10.1016/j.bbrc.2004.09.106
发表时间：
2004-11-12
影响因子：
3.1
作者：
He Y;Zhou Y;Liu S;Kou Z;Li W;Farzan M;Jiang S
通讯作者：
Jiang S
多器官感染和SAR的发病机理。
影响因子：
15.3
作者：
Gu, Jiang;Gong, Encong;Zhang, Bo;Zheng, Jie;Gao, Zifen;Zhong, Yanfeng;Zou, Wanzhong;Zhan, Jun;Wang, Shenglan;Xie, Zhigang;Zhuang, Hui;Wu, Bingquan;Zhong, Haohao;Shao, Hongquan;Fang, Weigang;Gao, Dongshia;Pei, Fei;Li, Xingwang;He, Zhongpin;Xu, Danzhen;Shi, Xeying;Anderson, Virginia M;Leong, Anthony S-Y
通讯作者：
Leong, Anthony S-Y