用于生产作为下一代脊髓灰质炎疫苗的稳定病毒样颗粒的重组表达系统

IF 15.7 1区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES
Lee Sherry, Mohammad W. Bahar, Claudine Porta, Helen Fox, Keith Grehan, Veronica Nasta, Helen M. E. Duyvesteyn, Luigi De Colibus, Johanna Marsian, Inga Murdoch, Daniel Ponndorf, Seong-Ryong Kim, Sachin Shah, Sarah Carlyle, Jessica J. Swanson, Sue Matthews, Clare Nicol, George P. Lomonossoff, Andrew J. Macadam, Elizabeth E. Fry, David I. Stuart, Nicola J. Stonehouse, David J. Rowlands
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引用次数: 0

摘要

几个世纪以来,脊髓灰质炎病毒一直在人类中造成致残疾病,这是在20世纪中期成功开发疫苗之前,疫苗大大降低了疾病流行率。然而,继续使用这些疫苗会威胁到最终消灭疾病和实现无脊髓灰质炎世界。缺乏病毒基因组的病毒样颗粒(vlp)代表了一种更安全的潜在疫苗,尽管它们需要颗粒稳定。利用我们先前建立的遗传技术来稳定结构衣壳蛋白,我们证明了从四种不同的重组表达系统生产所有三种血清型的脊髓灰质炎病毒VLPs。我们比较了这些稳定的VLPs与当前灭活脊髓灰质炎疫苗的抗原性、热稳定性和免疫原性,在雌性Wistar大鼠中显示出相同或更好的免疫原性。这些重组VLPs的结构分析为稳定突变和潜在赋形剂的作用提供了合理的理解。总的来说,我们已经确定这些脊髓灰质炎病毒稳定的vlp作为未来可行的下一代候选疫苗。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Recombinant expression systems for production of stabilised virus-like particles as next-generation polio vaccines

Recombinant expression systems for production of stabilised virus-like particles as next-generation polio vaccines

Polioviruses have caused crippling disease in humans for centuries, prior to the successful development of vaccines in the mid-1900’s, which dramatically reduced disease prevalence. Continued use of these vaccines, however, threatens ultimate disease eradication and achievement of a polio-free world. Virus-like particles (VLPs) that lack a viral genome represent a safer potential vaccine, although they require particle stabilization. Using our previously established genetic techniques to stabilize the structural capsid proteins, we demonstrate production of poliovirus VLPs of all three serotypes, from four different recombinant expression systems. We compare the antigenicity, thermostability and immunogenicity of these stabilized VLPs against the current inactivated polio vaccine, demonstrating equivalent or superior immunogenicity in female Wistar rats. Structural analyses of these recombinant VLPs provide a rational understanding of the stabilizing mutations and the role of potential excipients. Collectively, we have established these poliovirus stabilized VLPs as viable next-generation vaccine candidates for the future.

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来源期刊
Nature Communications
Nature Communications Biological Science Disciplines-
CiteScore
24.90
自引率
2.40%
发文量
6928
审稿时长
3.7 months
期刊介绍: Nature Communications, an open-access journal, publishes high-quality research spanning all areas of the natural sciences. Papers featured in the journal showcase significant advances relevant to specialists in each respective field. With a 2-year impact factor of 16.6 (2022) and a median time of 8 days from submission to the first editorial decision, Nature Communications is committed to rapid dissemination of research findings. As a multidisciplinary journal, it welcomes contributions from biological, health, physical, chemical, Earth, social, mathematical, applied, and engineering sciences, aiming to highlight important breakthroughs within each domain.
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