Wijesundara Yalini H, Arora Niyati, Ehrman Ryanne N, Howlett Thomas Sinclair, Weyman Trevor M, Trashi Ikeda, Trashi Orikeda, Kumari Sneha, Diwakara Shashini D, Tang Wendy, Senarathna Milinda C, Drewniak Katarzyna H, Wang Ziqi, Smaldone Ronald A, Gassensmith Jeremiah J
Department of Chemistry and Biochemistry, The University of Texas at Dallas, 800 West Campbell Rd, Richardson, 75080, TX, USA.
Department of Bioengineering, The University of Texas at Dallas, 800 West Campbell Rd, Richardson, 75080, TX, USA.
Angew Chem Int Ed Engl. 2025 Jan 27;64(5):e202413020. doi: 10.1002/anie.202413020. Epub 2024 Dec 16.
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.
疫苗是人类在公共卫生领域取得的最伟大成就之一，因为它们有助于预防疾病传播，降低发病率和死亡率，以极少的副作用拯救了成千上万的生命。传统疫苗研发主要围绕使用减毒活病原体或灭活病原体展开，这种方式成本高昂且导致了与疫苗相关的疾病。技术进步促使了更安全的亚单位疫苗的开发，这种疫苗包含从病原体中分离出的重组蛋白。大多数亚单位疫苗半衰期短、体积小，导致免疫原性较低。在此，我们介绍一种大孔二维共价有机框架（COF）——吡咯COF酰胺，它有望成为有效的亚单位疫苗平台。我们的研究表明，将模型抗原卵清蛋白（OVA）简单吸附到吡咯COF酰胺上（OVA@COF），与游离OVA相比，能显著增强体液免疫和细胞介导的免疫反应。OVA@COF表现出增强的免疫细胞激活作用，并作为抗原储存库，促进抗原呈递细胞向引流淋巴结的转运，放大体液免疫反应。此外，COF的分解会释放单体，这些单体可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途径。
