Chimeric severe acute respiratory syndrome coronavirus (SARS-CoV) S glycoprotein and influenza matrix 1 efficiently form virus-like particles (VLPs) that protect mice against challenge with SARS-CoV.

Chimeric severe acute respiratory syndrome coronavirus (SARS-CoV) S glycoprotein and influenza matrix 1 efficiently form virus-like particles (VLPs) that protect mice against challenge with SARS-CoV.
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DOI:
10.1016/j.vaccine.2011.06.111
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发表时间:
2011-09-02
期刊:
影响因子:
5.5
通讯作者:
Smith, Gale
Smith, Gale
中科院分区:
医学3区
文献类型:
--
作者:
Liu, Ye V.;Massare, Michael J.;Barnard, Dale L.;Kort, Thomas;Nathan, Margret;Wang, Lei;Smith, Gale

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sars冠状病毒是2003年全球大流行的原因,在8个月内感染了8000多人。目前还没有针对SARS的疫苗。我们开发了一种利用杆状病毒昆虫细胞表达系统生产高水平重组SARS病毒样颗粒(VLPs)疫苗的新方法,该疫苗含有SARS刺突(S)蛋白和流感M1蛋白。这些嵌合SARS VLPs具有与野生型SARS冠状病毒相似的大小和形态。我们在小鼠致死性攻毒模型中测试了纯化的嵌合SARS VLPs和全长SARS S蛋白疫苗的免疫原性和保护效果。SARS VLP疫苗含有0.8 μg的SARS S蛋白,在没有佐剂的情况下,通过肌肉注射(IM)或鼻内注射(IN)方式完全保护小鼠免于死亡。同样,含有4 μg无佐剂S蛋白的SARS VLP疫苗,将肺病毒滴度降低到可检测水平以下,保护小鼠免于体重减轻,并引发高水平的针对SARS冠状病毒的中和抗体。Sf9细胞产生的全长纯化SARS S蛋白也是一种有效的SARS- cov疫苗,但只有当IM与氢氧化铝共同给药时才有效。sars冠状病毒VLPs具有高度免疫原性,可诱导中和抗体,并提供抵抗致命挑战的保护。基于Sf9细胞的VLP疫苗是一种潜在的工具,可提供针对新型大流行病原体的保护。
SARS-CoV was the cause of the global pandemic in 2003 that infected over 8000 people in 8 months. Vaccines against SARS are still not available. We developed a novel method to produce high levels of a recombinant SARS virus-like particles (VLPs) vaccine containing the SARS spike (S) protein and the influenza M1 protein using the baculovirus insect cell expression system. These chimeric SARS VLPs have a similar size and morphology to the wild type SARS-CoV. We tested the immunogenicity and protective efficacy of purified chimeric SARS VLPs and full length SARS S protein vaccines in a mouse lethal challenge model. The SARS VLP vaccine, containing 0.8 μg of SARS S protein, completely protected mice from death when administered intramuscular (IM) or intranasal (IN) routes in the absence of an adjuvant. Likewise, the SARS VLP vaccine, containing 4 μg of S protein without adjuvant, reduced lung virus titer to below detectable level, protected mice from weight loss, and elicited a high level of neutralizing antibodies against SARS-CoV. Sf9 cell-produced full length purified SARS S protein was also an effective vaccine against SARS-CoV but only when co-administered IM with aluminum hydroxide. SARS-CoV VLPs are highly immunogenic and induce neutralizing antibodies and provide protection against lethal challenge. Sf9 cell-based VLP vaccines are a potential tool to provide protection against novel pandemic agents.
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