Dept. of Biomedical & Pharmaceutical Sciences, University of Montana, 32 Campus Dr, Missoula, MT 59812, USA.
Chem Commun (Camb). 2021 May 11;57(38):4698-4701. doi: 10.1039/d1cc00795e.
Despite the ease of production and improved safety profiles of recombinant vaccines, the inherently low immunogenicity of unadjuvanted proteins remains an impediment to their widespread adoption. The covalent tethering of TLR agonists to antigenic proteins offers a unique approach to co-deliver both constituents to the same cell-enhancing vaccine efficacy while minimizing reactogenicity. However, the paucity of simple and effective linker chemistries continues to hamper progress. Here, we present a modular, PEG-based linker system compatible with even extremely lipophilic and challenging TLR7/8 agonists. To advance the field and address previous obstacles, we offer the most straightforward and antigen-preserving linker system to date. These antigen-adjuvant conjugates enhance antigen-specific immune responses in mice, demonstrating the power of our approach within the context of modern vaccinology.
尽管重组疫苗的生产变得更加容易，且安全性有所提高，但未修饰蛋白固有地免疫原性低仍然是其广泛应用的障碍。TLR 激动剂与抗原蛋白的共价连接为共同递呈这两种成分提供了一种独特的方法，可增强疫苗效力，同时最小化其致反应原性。然而，简单有效的连接化学物质的缺乏继续阻碍了进展。在这里，我们提出了一种模块化的、基于 PEG 的连接系统，与即使是非常亲脂的和具有挑战性的 TLR7/8 激动剂也兼容。为了推进该领域并解决以前的障碍，我们提供了迄今为止最直接和抗原保存的连接系统。这些抗原-佐剂缀合物增强了小鼠的抗原特异性免疫反应，证明了我们的方法在现代疫苗学中的强大。
