Interdisciplinary Program in Immunology, University of Iowa, Iowa City, IA 52242.
Department of Molecular and Cell Biology, Centro Nacional de Biotecnolgia (CSIC), Campus Universidad Autonoma, Darwin 3, Cantoblanco, 28049 Madrid, Spain.
Virology. 2010 Mar 30;399(1):120-128. doi: 10.1016/j.virol.2010.01.004. Epub 2010 Jan 27.
The severe acute respiratory syndrome coronavirus (SARS-CoV) caused substantial morbidity and mortality in 2002-2003. Deletion of the envelope (E) protein modestly diminished virus growth in tissue culture but abrogated virulence in animals. Here, we show that immunization with rSARS-CoV-DeltaE or SARS-CoV-Delta[E,6-9b] (deleted in accessory proteins (6, 7a, 7b, 8a, 8b, 9b) in addition to E) nearly completely protected BALB/c mice from fatal respiratory disease caused by mouse-adapted SARS-CoV and partly protected hACE2 Tg mice from lethal disease. hACE2 Tg mice, which express the human SARS-CoV receptor, are extremely susceptible to infection. We also show that rSARS-CoV-DeltaE and rSARS-CoV-Delta[E,6-9b] induced anti-virus T cell and antibody responses. Further, the E-deleted viruses were stable after 16 blind passages through tissue culture cells, with only a single mutation in the surface glycoprotein detected. The passaged virus remained avirulent in mice. These results suggest that rSARS-CoV-DeltaE is an efficacious vaccine candidate that might be useful if SARS recurred.
严重急性呼吸综合征冠状病毒（SARS-CoV）在 2002-2003 年造成了大量发病率和死亡率。包膜（E）蛋白的缺失适度降低了组织培养中的病毒生长，但在动物中消除了毒力。在这里，我们表明，用 rSARS-CoV-DeltaE 或 SARS-CoV-Delta[E，6-9b]（除了 E 之外还缺失辅助蛋白（6、7a、7b、8a、8b、9b））免疫接种几乎完全保护 BALB/c 小鼠免受由适应小鼠的 SARS-CoV 引起的致命呼吸道疾病，并部分保护 hACE2 Tg 小鼠免受致命疾病。hACE2 Tg 小鼠表达人类 SARS-CoV 受体，极易感染。我们还表明，rSARS-CoV-DeltaE 和 rSARS-CoV-Delta[E，6-9b]诱导了抗病毒 T 细胞和抗体反应。此外，在细胞培养物中通过 16 次盲目传代后，E 缺失病毒仍然稳定，仅在表面糖蛋白中检测到单个突变。传代病毒在小鼠中仍无毒性。这些结果表明，rSARS-CoV-DeltaE 是一种有效的候选疫苗，如果 SARS 再次出现可能会很有用。
