摘要
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(TFH)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 TFH 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.
基金
supported by National Research Foundation(NRF)grants funded by the Korean government(grant numbers RS-2025-00513566 and RS-2023-00218648),Republic of Korea(Prof.Yong Taik Lim)
supported by NRF grants funded by Korean government(grant number 2021R1A6A1A03045495),Republic of Korea(Prof.Jong-Soo Lee)
supported by the Institute for Basic Science(grant number IBS-R801-D1),Republic of Korea(Director Young Ki Choi).
