Yoo Yeon Jeong, Kim Suhyeon, Wickramasinghe Asha, Kim Jaemoo, Song JuA, Kim Young-Il, Gil Juryeon, Noh Young-Woock, Lee Min-Ho, Oh Sang-Seok, Lee Myeong-Mi, Seong Yebin, Lee Jong-Soo, Choi Yong Ki, Lim Yong Taik
SKKU Advanced Institute of Nanotechnology (SAINT), Department of Nano Science and Technology, Department of Nano Engineering, School of Chemical Engineering, and Biomedical Institute for Convergence at SKKU, Sungkyunkwan University, Suwon, Republic of Korea.
College of Veterinary Medicine, Chungnam National University, Daejeon, Republic of Korea.
Cell Mol Immunol. 2025 Jun 25. doi: 10.1038/s41423-025-01306-6.
The demand for safe vaccines that ensure long-term and broad protection against multiple viral variants has dramatically increased after the emergence of catastrophic infectious diseases such as COVID-19. To ensure long-term and broad protection against heterologous virus variants, antigen-specific polyfunctional T cells should be orchestrated with the activation of follicular helper T (T) cells and germinal center (GC) B cells. Herein, we suggest a novel engineered nanoadjuvant (SE(Trojan-TLR7/8a)) that enhances the migration of nonexhausted antigen-presenting cells (APCs) into lymph nodes and elicits the activation of T cells, the generation of GC B cells, and polyfunctional T cells via multiscale dynamic immunomodulation through squalene nanoemulsion (SE)-mediated macroscopic control of vaccine delivery and Trojan-TLR7/8a-enabled dynamic and sustained activation of APCs at the cellular level. SE(Trojan-TLR7/8a) can be lyophilized, reduce systemic toxicity, and outperform current commercial vaccine adjuvants (Alum or AS03) and mRNA vaccines. SE(Trojan-TLR7/8a) ensures cross-protection against diverse influenza and SARS-CoV-2 variants, providing 100% protection while maintaining a healthy state. SE(Trojan-TLR7/8a) also sustains a potent T-cell response in an aged ferret model of SFTSV infection. SE(Trojan-TLR7/8a) suggested herein provides a novel vaccine design principle for dynamic modulation at the multiscale level and demonstrates long-term and broad protective immunity against emerging pandemic and endemic infectious viruses.
在COVID-19等灾难性传染病出现后，对能确保长期广泛抵御多种病毒变体的安全疫苗的需求急剧增加。为确保对异源病毒变体的长期广泛保护，应通过激活滤泡辅助性T（Th）细胞和生发中心（GC）B细胞来协调抗原特异性多功能T细胞。在此，我们提出一种新型工程纳米佐剂（SE(Trojan-TLR7/8a)），它可增强未耗竭抗原呈递细胞（APC）向淋巴结的迁移，并通过角鲨烯纳米乳剂（SE）介导的疫苗递送宏观控制以及Trojan-TLR7/8a在细胞水平实现的APC动态持续激活，通过多尺度动态免疫调节引发T细胞激活、GC B细胞生成和多功能T细胞。SE(Trojan-TLR7/8a)可冻干，降低全身毒性，并且优于目前的商业疫苗佐剂（明矾或AS03）和mRNA疫苗。SE(Trojan-TLR7/8a)确保对多种流感和SARS-CoV-2变体的交叉保护，提供100%保护并维持健康状态。SE(Trojan-TLR7/8a)在老年白鼬发热伴血小板减少综合征病毒（SFTSV）感染模型中也能维持强大的T细胞应答。本文提出的SE(Trojan-TLR7/8a)提供了一种多尺度动态调节的新型疫苗设计原则，并证明了对新出现的大流行和地方性感染病毒具有长期广泛的保护性免疫。
