Protective humoral responses to severe acute respiratory syndrome-associated coronavirus: implications for the design of an effective protein-based vaccine

Protective humoral responses to severe acute respiratory syndrome-associated coronavirus: implications for the design of an effective protein-based vaccine
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DOI:
10.1099/vir.0.80111-0
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发表时间:
2004-10-01
影响因子:
3.8
通讯作者:
Rao, ZH
Rao, ZH
中科院分区:
医学3区
文献类型:
--
作者:
Hai, P;Liu, YG;Rao, ZH

文献摘要

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严重急性呼吸综合征相关冠状病毒(SARS - CoV)的一些结构蛋白携带参与病毒中和的主要表位,对诱导保护性体液免疫应答和开发有效疫苗至关重要。利用全长N蛋白和M蛋白以及覆盖S蛋白的8个表达片段制备了兔抗血清。发现针对S蛋白和M蛋白的抗血清在体内对SARS - CoV感染具有不同的中和效价,范围从1∶35到1∶128。针对N蛋白的抗血清不含有中和抗体。诱导针对病毒感染的保护性体液免疫应答的表位主要位于M蛋白以及S蛋白跨越13 - 877位氨基酸的区域。针对表达的结构蛋白的抗血清的中和能力强于恢复期患者抗血清,证实了作为免疫原,前者可诱导强烈的、针对SARS - CoV的特异性中和抗体应答。体外中和试验对设计一种预防SARS - CoV感染的有效的、基于蛋白质的疫苗具有重要意义。
Some of the structural proteins of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) carry major epitopes involved in virus neutralization and are essential for the induction of protective humoral responses and the development of an effective vaccine. Rabbit antisera were prepared using full-length N and M proteins and eight expressed fragments covering the S protein. Antisera to S and M proteins were found to have different neutralizing titres towards SARS-CoV infection in vivo, ranging from 1 : 35 to 1 : 128. Antiserum to the N protein did not contain neutralizing antibodies. Epitopes inducing protective humoral responses to virus infection were located mainly in the M protein and a region spanning residues 13-877 of the S protein. The neutralizing ability of antisera directed against the expressed structural proteins was greater than that of convalescent patient antisera, confirming that, as immunogens, the former induce strong, SARS-CoV-specific neutralizing antibody responses. The in vitro neutralization assay has important implications for the design of an effective, protein-based vaccine preventing SARS-CoV infection.