Expression and characterization of SARS-CoV-2 spike protein in Thermothelomyces heterothallica C1

IF 4.5 3区医学 Q2 IMMUNOLOGY

Vaccine Pub Date : 2025-09-29 DOI:10.1016/j.vaccine.2025.127784

Yakir Ophir , Justin H. Wong , Katherine R. Haddad , Anne Huuskonen , Anindya Karmaker , Varun Gore , Seongwon Jung , Armin Oloumi , Yiyun Liu , Jingxin Fu , Libo Zhang , Peishan Huang , Shiaki Arnett Minami , Shruthi Satya Garimella , Anugraha Thyagatur , Paulo A. Zaini , Marika Vitikainen , Ronen Tchelet , Noelia Valbuena , Thomas R. Fuerst , Somen Nandi

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引用次数: 0

Abstract

The COVID-19 pandemic demonstrated a pressing need for rapid, adaptive, and scalable manufacturing of vaccines and reagents. With the transition into an endemic disease and rising threats of other emerging pandemics, production of these biologicals requires a stable and sustainable supply chain and accessible distribution methods. In this study, we demonstrate the strength of an engineered filamentous fungal platform, Thermothelomyces heterothallica C1, for high volumetric productivity of the full-length spike glycoprotein. Spike protein produced in this system is highly thermostable and immunization of mice with spike made in C1 or mammalian platforms resulted in a similar humoral response. Additionally, it was shown that the native N-glycan profile can be redecorated with complex sialylated structures, if necessary, resulting in a more human-like glycan profile, without impacting binding characteristics as shown experimentally and in simulations. Through extensive physicochemical analysis, the C1-produced spike performs similarly to spike proteins produced in other commercially available systems. The data presented is evidence that C1 can be a strong platform for production of complex glycosylated recombinant proteins such as subunit antigen vaccines.

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SARS-CoV-2刺突蛋白在异菌热thelomyces heterothallica C1中的表达与特性

COVID-19大流行表明，迫切需要快速、适应和可扩展地生产疫苗和试剂。随着向地方病的转变和其他新出现的大流行病的威胁日益增加，这些生物制剂的生产需要一个稳定和可持续的供应链和易于获得的分销方法。在这项研究中，我们展示了一种工程丝状真菌平台的强度，热thelomyces heterothallica C1，对于全长刺状糖蛋白的高容量生产力。该系统产生的刺突蛋白具有高度的热稳定性，在C1或哺乳动物平台上产生刺突的小鼠免疫产生类似的体液反应。此外，研究表明，如果有必要，天然n-聚糖结构可以用复杂的唾液化结构重新修饰，从而产生更像人类的聚糖结构，而不会影响实验和模拟所显示的结合特性。通过广泛的物理化学分析，c1生产的刺突蛋白与其他市售系统生产的刺突蛋白性能相似。所提供的数据证明，C1可以成为生产复杂糖基化重组蛋白（如亚单位抗原疫苗）的强大平台。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Vaccine 医学-免疫学

CiteScore

8.70

自引率

5.50%

发文量

992

审稿时长

131 days

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