Lymph node (LN) targeting and antigen presentation by antigen-presenting cells (APCs) are critical factors affecting the immune responses induced by tumor vaccines. Autophagy activation promotes MHC class I and II antigen presentation in APCs. To enhance antigen presentation in LNs, we developed an aluminum hydroxide nanovaccine that simultaneously incorporates the autophagy-activating peptide Beclin-1 and the antigenic protein OVA (B/O@AN nanovaccine) through layer-by-layer electrostatic interaction. B/O@AN has a particle size of approximately 80 nm and efficiently targets lymph nodes following subcutaneous administration. The combination of the Beclin-1 peptide with the aluminum hydroxide nanovaccine promotes dendritic cell (DC) maturation. More importantly, B/O@AN facilitates antigen cross-presentation by promoting lysosomal escape and autophagy induction. After immunization, compared to O/@AN without Beclin-1, B/O@AN significantly augments antigen-specific cellular immune responses, leading to substantial increases in cytotoxic T lymphocytes (CTLs), T-helper 1 (Th1) cells, as well as serum antibody levels, thereby impeding melanoma development and progression in both prophylactic and therapeutic settings. These results provide evidence that autophagy activation strengthens antigen presentation and augments the antigen-specific immune responses of the aluminum hydroxide nanovaccine.

中文翻译：

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自噬激活氢氧化铝纳米疫苗，用于增强抗原呈递和抗肿瘤免疫


抗原呈递细胞 （APC） 的淋巴结 （LN） 靶向和抗原呈递是影响肿瘤疫苗诱导的免疫反应的关键因素。自噬激活促进 APC 中 MHC I 类和 II 类抗原的呈递。为了增强 LN 中的抗原呈递，我们开发了一种氢氧化铝纳米疫苗，该疫苗通过逐层静电相互作用同时掺入自噬激活肽 Beclin-1 和抗原蛋白 OVA （B/O@AN 纳米疫苗）。B/O@AN 的粒径约为 80 nm，可在皮下给药后有效靶向淋巴结。Beclin-1 肽与氢氧化铝纳米疫苗的结合促进了树突状细胞 （DC） 的成熟。更重要的是，B/O@AN 通过促进溶酶体逃逸和自噬诱导来促进抗原交叉呈递。免疫后，与不含 Beclin-1 的 O/@AN 相比，B/O@AN 显着增强抗原特异性细胞免疫反应，导致细胞毒性 T 淋巴细胞 （CTL）、T 辅助细胞 1 （Th1） 细胞以及血清抗体水平显着增加，从而阻碍黑色素瘤在预防和治疗环境中的发展和进展。这些结果提供了证据，证明自噬激活增强了氢氧化铝纳米疫苗的抗原呈递并增强了抗原特异性免疫反应。