Institute of Traditional Chinese Veterinary Medicine, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, Jiangsu 210095, PR China; MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, Jiangsu 210095, PR China.
MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, Jiangsu 210095, PR China.
Biomed Pharmacother. 2024 Aug;177:117036. doi: 10.1016/j.biopha.2024.117036. Epub 2024 Jun 27.
Vaccines are an effective intervention for preventing infectious diseases. Currently many vaccine strategies are designed to improve vaccine efficacy by controlling antigen release, typically involving various approaches at the injection site. Yet, strategies for intracellular slow-release of antigens in vaccines are still unexplored. Our study showed that controlling the degradation of antigens in dendritic cells and slowing their transport from early endosomes to lysosomes markedly enhances both antigen-specific T-cell immune responses and germinal center B cell responses. This leads to the establishment of sustained humoral and cellular immunity in vivo imaging and flow cytometry indicated this method not only prolongs antigen retention at the injection site but also enhances antigen concentration in lymph nodes, surpassing traditional Aluminium (Alum) adjuvants. Additionally, we demonstrated that the slow antigen degradation induces stronger follicular helper T cell responses and increases proportions of long-lived plasma cells and memory B cells. Overall, these findings propose that controlling the speed of antigens transport in dendritic cells can significantly boost vaccine efficacy, offering an innovative avenue for developing highly immunogenic next-generation vaccines.
疫苗是预防传染病的有效干预措施。目前,许多疫苗策略旨在通过控制抗原释放来提高疫苗的疗效,通常涉及在注射部位的各种方法。然而,疫苗中抗原的细胞内缓慢释放策略仍未被探索。我们的研究表明,控制树突状细胞中抗原的降解并减缓其从早期内体到溶酶体的运输,显著增强了抗原特异性 T 细胞免疫应答和生发中心 B 细胞应答。这导致在体内建立持续的体液和细胞免疫。体内成像和流式细胞术表明,这种方法不仅延长了注射部位的抗原保留时间,而且增强了淋巴结中的抗原浓度,超过了传统的铝(Alum)佐剂。此外,我们证明缓慢的抗原降解诱导更强的滤泡辅助 T 细胞应答,并增加了长寿浆细胞和记忆 B 细胞的比例。总的来说,这些发现表明控制树突状细胞中抗原运输的速度可以显著提高疫苗的疗效,为开发具有高度免疫原性的下一代疫苗提供了一种创新途径。