激活纳米颗粒疫苗在淋巴结中的体液和细胞免疫对于控制肿瘤至关重要。然而，纳米疫苗载体的物理特性如何在淋巴结中调控抗原捕获、淋巴运输、抗原呈递和免疫应答，目前还知之甚少。本研究制备了同样尺寸但不同形状（笼状、棒状和星状）的金纳米颗粒（AuNPs），并将肿瘤抗原作为纳米疫苗进行载药，探究它们在上述四个领域的差异性。结果显示，星状AuNPs捕获和保留了更多的重复性抗原表位。在淋巴传递方面，棒状和星状纳米疫苗主要排入淋巴结滤泡区，而笼状纳米疫苗则表现出更强的副皮质滞留。一个令人惊讶的发现是，星状纳米疫苗引起了强效的体液免疫，这是由CD4+辅助T细胞和滤泡B细胞合作介导的，在预防性研究中显著地防止了肿瘤生长。有趣的是，笼状纳米疫苗更倾向于呈递肽-MHC I复合物以引起强效的CD8+T细胞免疫，在已建立肿瘤的研究中与PD-1检查点抑制剂联合应用时显示出最强的治疗效果。这些结果突出了纳米颗粒形状在淋巴结抗原传递和呈递中对免疫应答的重要性，并支持了不同设计策略在预防性和治疗性疫苗中的需求。©2023中国药学协会和中国医学科学院药物研究所。Elsevier B.V.进行生产和托管。

Activating humoral and cellular immunity in lymph nodes (LNs) of nanoparticle-based vaccines is critical to controlling tumors. However, how the physical properties of nanovaccine carriers orchestrate antigen capture, lymphatic delivery, antigen presentation and immune response in LNs is largely unclear. Here, we manufactured gold nanoparticles (AuNPs) with the same size but different shapes (cages, rods, and stars), and loaded tumor antigen as nanovaccines to explore their disparate characters on above four areas. Results revealed that star-shaped AuNPs captured and retained more repetitive antigen epitopes. On lymphatic delivery, both rods and star-shaped nanovaccines mainly drain into the LN follicles region while cage-shaped showed stronger paracortex retention. A surprising finding is that the star-shaped nanovaccines elicited potent humoral immunity, which is mediated by CD4+ T helper cell and follicle B cell cooperation significantly preventing tumor growth in the prophylactic study. Interestingly, cage-shaped nanovaccines preferentially presented peptide-MHC I complexes to evoke robust CD8+ T cell immunity and showed the strongest therapeutic efficacy when combined with the PD-1 checkpoint inhibitor in established tumor study. These results highlight the importance of nanoparticle shape on antigen delivery and presentation for immune response in LNs, and our findings support the notion that different design strategies are required for prophylactic and therapeutic vaccines.© 2023 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.