A platform technology for generating subunit vaccines against diverse viral pathogens.
A platform technology for generating subunit vaccines against diverse viral pathogens.
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DOI：
10.3389/fimmu.2022.963023
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发表时间：
2022
影响因子：
7.3
通讯作者：
Watterson D
中科院分区：
文献类型：
--
作者：
Young A;Isaacs A;Scott CAP;Modhiran N;McMillan CLD;Cheung STM;Barr J;Marsh G;Thakur N;Bailey D;Li KSM;Luk HKH;Kok KH;Lau SKP;Woo PCY;Furuyama W;Marzi A;Young PR;Chappell KJ;Watterson D
2019冠状病毒病大流行的应对措施表明，疫苗平台技术可用于快速有效地对抗新型传染病。基于mRNA和载体的疫苗的开发速度超过了亚单位疫苗，然而，亚单位疫苗在安全性和稳定性方面具有优势。在这里，我们描述了一种亚单位疫苗平台技术，分子钳，应用于来自不同分类家族的四种病毒：中东呼吸综合征冠状病毒（MERS-CoV），埃博拉病毒（EBOV），拉沙病毒（LASV）和尼帕病毒（NiV）。所述夹通过稳定三聚体病毒融合蛋白的免疫学上重要的融合前表位，同时通过充当亲和标签使得能够在没有靶特异性试剂的情况下进行纯化，从而简化了亚单位抗原的产生。通过单克隆抗体结合、尺寸排阻色谱法和电子显微镜证实每种病毒抗原的构象。值得注意的是，所有四种测试的抗原在40°C下孵育四周后保持稳定。在测试的四种疫苗中，通过钳稳定的MERS-CoV刺突、EBOV糖蛋白和NiV融合蛋白刺激中和免疫应答。只有钳稳定的LASV糖蛋白前体不能引起病毒中和抗体。MERS-CoV和EBOV候选疫苗都在动物模型中进行了测试，发现可以提供针对病毒攻击的保护。
The COVID-19 pandemic response has shown how vaccine platform technologies can be used to rapidly and effectively counteract a novel emerging infectious disease. The speed of development for mRNA and vector-based vaccines outpaced those of subunit vaccines, however, subunit vaccines can offer advantages in terms of safety and stability. Here we describe a subunit vaccine platform technology, the molecular clamp, in application to four viruses from divergent taxonomic families: Middle Eastern respiratory syndrome coronavirus (MERS-CoV), Ebola virus (EBOV), Lassa virus (LASV) and Nipah virus (NiV). The clamp streamlines subunit antigen production by both stabilising the immunologically important prefusion epitopes of trimeric viral fusion proteins while enabling purification without target-specific reagents by acting as an affinity tag. Conformations for each viral antigen were confirmed by monoclonal antibody binding, size exclusion chromatography and electron microscopy. Notably, all four antigens tested remained stable over four weeks of incubation at 40°C. Of the four vaccines tested, a neutralising immune response was stimulated by clamp stabilised MERS-CoV spike, EBOV glycoprotein and NiV fusion protein. Only the clamp stabilised LASV glycoprotein precursor failed to elicit virus neutralising antibodies. MERS-CoV and EBOV vaccine candidates were both tested in animal models and found to provide protection against viral challenge.
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影响因子：
16.8
作者：
通讯作者：
--
DOI：
10.1038/nbt1088-1204
发表时间：
1988-10-01
期刊：
BIO-TECHNOLOGY
影响因子：
--
作者：
HOPP, TP;PRICKETT, KS;CONLON, PJ
通讯作者：
CONLON, PJ
影响因子：
5.9
作者：
Hastie, Kathryn M.;Saphire, Erica Mann
通讯作者：
Saphire, Erica Mann
影响因子：
6.4
作者：
Cai, Yingyun;Ye, Chengjin;Martinez-Sobrido, Luis
通讯作者：
Martinez-Sobrido, Luis
组合F-G免疫原作为NIPAH和呼吸道合胞病毒疫苗候选。
DOI：
10.3390/v13101942
发表时间：
2021-09-28
期刊：
Viruses
影响因子：
--
作者：
Isaacs A;Cheung STM;Thakur N;Jaberolansar N;Young A;Modhiran N;Bailey D;Graham SP;Young PR;Chappell KJ;Watterson D
通讯作者：
Watterson D