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A Self‐Adjuvanting Large Pore 2D Covalent Organic Framework as a Vaccine Platform
Angewandte Chemie International Edition ( IF 16.1 ) Pub Date : 2024-12-02 , DOI: 10.1002/anie.202413020
Yalini H. Wijesundara, Niyati Arora, Ryanne N. Ehrman, Trevor M. Weyman, Thomas Sinclair Howlett, Ikeda Trashi, Orikeda Trashi, Sneha Kumari, Wendy Tang, Milinda C. Senarathna, Katarzyna H. Drewniak, Ziqi Wang, Shashini D. Diwakara, Ronald A. Smaldone, Jeremiah Gassensmith

Vaccines are one of the greatest human achievements in public health, as they help prevent the spread of diseases, reduce illness and death rates, saving thousands of lives with few side effects. Traditional vaccine development is centered around using live attenuated or inactivated pathogens, which is expensive and has resulted in vaccine‐associated illnesses. Advancements have led to the development of safer subunit vaccines, which contain recombinant proteins isolated from pathogens. Their short half‐life and small size make most subunit vaccines less immunogenic. Here, we introduce a large pore 2D covalent organic framework (COF), PyCOFamide, as a promising solution for an effective subunit platform. Our study demonstrates that simple adsorption of a model antigen, ovalbumin (OVA), onto PyCOFamide (OVA@COF) significantly enhances humoral and cell‐mediated immune response compared to free OVA. OVA@COF exhibited heightened immune cell activation and acts as an antigen reservoir, facilitating antigen‐presenting cell trafficking to the draining lymph nodes, amplifying the humoral immune response. Additionally, the breakdown of the COF releases monomers that adjuvant the activation of immune cells vital to creating strong immunity. This platform offers a potential avenue for safer, more effective subunit vaccines.

中文翻译:


自佐剂大孔 2D 共价有机框架作为疫苗平台



疫苗是人类在公共卫生领域最伟大的成就之一,因为它们有助于防止疾病传播、降低疾病和死亡率,挽救数千人的生命,而且副作用很小。传统的疫苗开发以使用减毒或灭活病原体为中心,这很昂贵,并导致了与疫苗相关的疾病。进步导致了更安全的亚单位疫苗的开发,其中包含从病原体中分离的重组蛋白。它们的半衰期短且体积小,使大多数亚单位疫苗的免疫原性较低。在这里,我们介绍了一个大孔 2D 共价有机框架 (COF) PyCOFamide,作为有效亚基平台的一个有前途的解决方案。我们的研究表明,与游离 OVA 相比,模型抗原卵清蛋白 (OVA) 的简单吸附到 PyCOFamide (OVA@COF) 上可显着增强体液和细胞介导的免疫反应。OVA@COF表现出增强的免疫细胞活化并充当抗原库,促进抗原呈递细胞运输到引流淋巴结,放大体液免疫反应。此外,COF 的分解会释放单体,这些单体辅助激活对产生强大免疫力至关重要的免疫细胞。该平台为更安全、更有效的亚单位疫苗提供了一条潜在的途径。
更新日期:2024-12-02
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