Inactivated SARS-CoV vaccine elicits high titers of spike protein-specific antibodies that block receptor binding and virus entry.

Inactivated SARS-CoV vaccine elicits high titers of spike protein-specific antibodies that block receptor binding and virus entry.
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灭活的SARS-COV疫苗会引起高峰蛋白特异性抗体的高滴度,这些抗体阻断受体结合和病毒的进入。

DOI:
10.1016/j.bbrc.2004.10.052
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发表时间:
2004-12-10
影响因子:
3.1
通讯作者:
Jiang S
Jiang S
中科院分区:
生物学4区
文献类型:
--
作者:
He Y;Zhou Y;Siddiqui P;Jiang S

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目前正在进行临床试验的唯一严重急性呼吸综合征(SARS)疫苗由灭活的严重急性呼吸综合征相关冠状病毒(SARS-CoV)组成。然而,关于灭活SARS疫苗诱导的宿主免疫应答的信息有限。在本研究中,我们证明了经β-丙内酯灭活的SARS-CoV在免疫的小鼠和家兔中引发了高滴度的抗体,这些抗体识别S蛋白,特别是S1区的受体结合结构域(RBD)。来自免疫动物的抗血清有效地结合RBD并阻断RBD与SARS-CoV易感细胞上的功能性受体血管紧张素转换酶2的结合。利用携带SARS-CoV S蛋白的假病毒进行敏感和定量的单循环感染试验,我们证明小鼠和兔抗血清显著抑制S蛋白介导的病毒进入,平均50%抑制滴度分别为1:7393和1:2060。这些数据表明,S蛋白的RBD是灭活SARS疫苗中的主要中和决定簇,其可以诱导有效的中和抗体来阻断SARS-CoV的进入。然而,在使用灭活的SARS-CoV作为疫苗时应谨慎,因为它也可能引起有害的免疫和/或炎症反应。
The only severe acute respiratory syndrome (SARS) vaccine currently being tested in clinical trial consists of inactivated severe acute respiratory syndrome-associate coronavirus (SARS-CoV). However, limited information is available about host immune responses induced by the inactivated SARS vaccine. In this study, we demonstrated that SARS-CoV inactivated by β-propiolactone elicited high titers of antibodies in the immunized mice and rabbits that recognize the spike (S) protein, especially the receptor-binding domain (RBD) in the S1 region. The antisera from the immunized animals efficiently bound to the RBD and blocked binding of RBD to angiotensin-converting enzyme 2, the functional receptor on the susceptible cells for SARS-CoV. With a sensitive and quantitative single-cycle infection assay using pseudovirus bearing the SARS-CoV S protein, we demonstrated that mouse and rabbit antisera significantly inhibited S protein-mediated virus entry with mean 50% inhibitory titers of 1:7393 and 1:2060, respectively. These data suggest that the RBD of S protein is a major neutralization determinant in the inactivated SARS vaccine which can induce potent neutralizing antibodies to block SARS-CoV entry. However, caution should be taken in using the inactivated SARS-CoV as a vaccine since it may also cause harmful immune and/or inflammatory responses.
DOI: 10.1016/j.bbrc.2004.01.076
发表时间: 2004-03-05
影响因子: 3.1
作者:
Wang P;Chen J;Zheng A;Nie Y;Shi X;Wang W;Wang G;Luo M;Liu H;Tan L;Song X;Wang Z;Yin X;Qu X;Wang X;Qing T;Ding M;Deng H
通讯作者: Deng H
DOI: 10.1074/jbc.m400759200
发表时间: 2004-05-14
期刊: The Journal of biological chemistry
影响因子: --
作者:
Tripet B;Howard MW;Jobling M;Holmes RK;Holmes KV;Hodges RS
通讯作者: Hodges RS
DOI: 10.1038/nature02145
发表时间: 2003-11-27
期刊: Nature
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
DOI: 10.1016/s0092-8674(03)00976-0
发表时间: 2003-12-12
期刊: Cell
影响因子: 64.5
作者:
Dimitrov DS
通讯作者: Dimitrov DS
DOI: 10.1016/s0140-6736(03)13077-2
发表时间: 2003-04-19
期刊: Lancet (London, England)
影响因子: --
作者:
Peiris JS;Lai ST;Poon LL;Guan Y;Yam LY;Lim W;Nicholls J;Yee WK;Yan WW;Cheung MT;Cheng VC;Chan KH;Tsang DN;Yung RW;Ng TK;Yuen KY;SARS study group
通讯作者: SARS study group