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基于酵母孢子表面展示系统开发口服疫苗的新型平台的建立。

Establishment of a Novel Platform for Developing Oral Vaccines Based on the Surface Display System of Yeast Spores.

作者信息

Si Chenyu, Bai Jiawen, Li Yuqing, Li Yang, Liu Yishi, Zhou Xiaoman, Shi Jie, Nakanishi Hideki, Li Zijie

机构信息

Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi 214122, China.

出版信息

Int J Mol Sci. 2025 Apr 11;26(8):3615. doi: 10.3390/ijms26083615.

Abstract

Oral vaccines are currently the focus of vaccine development because they are convenient to administer, easy to distribute, and capable of activating mucosal immunity. However, the complexity of the gastrointestinal environment and the lack of delivery vehicles severely limit the stability and effectiveness of oral vaccines. This study established a novel platform for developing oral vaccines based on the surface display system of yeast spores. As a specific example, oral vaccines for COVID-19, designed by displaying the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein on the surface of three spore types, including AN120, Δ, and Δ, were constructed and evaluated. The displayed RBD showed perfect gastrointestinal stability in vitro and was validated in animal studies to produce effective humoral immunity and significant mucosal immune responses after the vaccination. Notably, the displayed RBD elicited a cellular immune response skewed towards a T-helper type 1 (Th1) cell direction in a mouse model. Our findings proved that the oral vaccines of spores could rapidly induce a comprehensive and protective immune response to SARS-CoV-2. This study aims to provide a promising and potentially useful system that can be used to develop other oral vaccines.

摘要

口服疫苗目前是疫苗研发的重点,因为它们给药方便、易于分发,并且能够激活黏膜免疫。然而,胃肠道环境的复杂性和递送载体的缺乏严重限制了口服疫苗的稳定性和有效性。本研究基于酵母孢子表面展示系统建立了一种新型口服疫苗研发平台。作为一个具体实例,构建并评估了通过在三种孢子类型(包括AN120、Δ和Δ)表面展示严重急性呼吸综合征冠状病毒2(SARS-CoV-2)刺突蛋白的受体结合域(RBD)而设计的COVID-19口服疫苗。展示的RBD在体外表现出完美的胃肠道稳定性,并在动物研究中得到验证,接种疫苗后可产生有效的体液免疫和显著的黏膜免疫反应。值得注意的是,在小鼠模型中,展示的RBD引发了偏向1型辅助性T细胞(Th1)方向的细胞免疫反应。我们的研究结果证明,孢子口服疫苗能够快速诱导针对SARS-CoV-2的全面保护性免疫反应。本研究旨在提供一个有前景且可能有用的系统,可用于研发其他口服疫苗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/378e/12026953/61ad676168eb/ijms-26-03615-g001.jpg

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