Recombinant H7 hemagglutinin forms subviral particles that protect mice and ferrets from challenge with H7N9 influenza virus.
Recombinant H7 hemagglutinin forms subviral particles that protect mice and ferrets from challenge with H7N9 influenza virus.
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DOI：
10.1016/j.vaccine.2015.07.026
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发表时间：
2015-09-11
期刊：
影响因子：
5.5
通讯作者：
Tumpey TM
中科院分区：
文献类型：
--
作者：
Pushko P;Pujanauski LM;Sun X;Pearce M;Hidajat R;Kort T;Schwartzman LM;Tretyakova I;Chunqing L;Taubenberger JK;Tumpey TM
一种新型禽流感H7N9病毒于2013年在中国出现，并继续造成人的零星感染，死亡率接近35%。目前还没有批准的针对H7N9病毒的人类疫苗。包括血凝素(HA)和病毒样颗粒(VLP)在内的重组方法已经导致了具有良好安全性和制造特性的实验疫苗。虽然VLP疫苗的高免疫原性归因于HA的天然构象在类病毒结构中以规则的重复模式排列，但关于重组HA疫苗制剂中HA的分子组织的数据有限。本研究在Sf9细胞中表达了A/安徽/1/2013(H7N9)病毒全长重组H7蛋白(Rh7)。我们发现，纯化的全长Rh7保留了凝集红细胞的功能，并形成了直径约20 nm的寡聚体多形亚病毒颗粒(SVP)，由大约10个HA0分子组成。通过尺寸排除层析，在Rh7制剂中没有观察到显著数量的游离单体HA0。在小鼠和雪貂攻击模型中证实了Rh7SVPS的免疫原性和保护效果，表明SVPS可用于H7N9病毒的疫苗接种。
A novel avian-origin influenza A H7N9 virus emerged in China in 2013 and continues to cause sporadic human infections with mortality rates approaching 35%. Currently there are no approved human vaccines for H7N9 virus. Recombinant approaches including hemagglutinin (HA) and virus-like particles (VLPs) have resulted in experimental vaccines with advantageous safety and manufacturing characteristics. While high immunogenicity of VLP vaccines has been attributed to the native conformation of HA arranged in the regular repeated patterns within virus-like structures, there is limited data regarding molecular organization of HA within recombinant HA vaccine preparations. In this study, the full-length recombinant H7 protein (rH7) of A/Anhui/1/2013 (H7N9) virus was expressed in Sf9 cells. We showed that purified full-length rH7 retained functional ability to agglutinate red blood cells and formed oligomeric pleomorphic subviral particles (SVPs) of ~20 nm in diameter composed of approximately 10 HA0 molecules. No significant quantities of free monomeric HA0 were observed in rH7 preparation by size exclusion chromatography. Immunogenicity and protective efficacy of rH7 SVPs was confirmed in the mouse and ferret challenge models suggesting that SVPs can be used for vaccination against H7N9 virus.