Due to its safety and efficacy, aluminum hydroxide is used as an immune adjuvant in human vaccines for over 80 years. Being a Th2 stimulator, the classical gel‐like adjuvant, however, fails to generate CD8⁺ T cell responses, which are important for cancer vaccines. Here, aluminum hydroxide is turned from gel into nano‐sized vaccine carriers AlO(OH)‐polymer nanoparticles (APNs) to promote their lymphatic migration. After actively uptaken via scavenger receptor‐A by antigen‐presenting cells (APCs) resident in lymph nodes (LNs), APNs destabilize lysosomes resulting in efficient cytosolic delivery and cross‐presentation of antigens. It is demonstrated that administration of APNs loaded with ovalbumin (OVA) and CpG led to the codelivery of both cargos into APCs in LNs, leading to their activation and subsequent adaptive immunity. A prime‐boost strategy with low doses of OVA (1.5 µg) and CpG (0.45 µg) induces potent CD8⁺ T cell responses and dramatically prolongs the survival of B16‐OVA tumor‐bearing mice. More impressively, when using B16F10 lysates instead of OVA as antigen, substantial antitumor effects on B16F10 tumor model are observed by using APN‐CpG. These results suggest the great potential of APNs as vaccine carriers that activate CD8⁺ T cell responses and the bright prospect of aluminum adjuvant in a nanoparticle formulation.

中文翻译：

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将旧佐剂从凝胶转变为纳米颗粒以增强 CD8+ T 细胞反应

由于其安全性和有效性，氢氧化铝在人类疫苗中用作免疫佐剂已有 80 多年的历史。然而，作为 Th2 刺激剂，经典的凝胶状佐剂无法产生对于癌症疫苗很重要的CD8 ^{+ T 细胞反应。}在这里，氢氧化铝从凝胶转变为纳米尺寸的疫苗载体 AlO(OH)-聚合物纳米颗粒 (APN)，以促进其淋巴迁移。APNs 通过清道夫受体 A 被淋巴结 (LN) 中的抗原呈递细胞 (APC) 主动摄取后，会破坏溶酶体的稳定性，从而实现抗原的有效胞质递送和交叉呈递。结果表明，施用负载有卵清蛋白 (OVA) 和 CpG 的 APN 会导致两种货物同时递送到 LN 中的 APC 中，从而导致它们的激活和随后的适应性免疫。采用低剂量 OVA (1.5 µg) 和 CpG (0.45 µg) 的初免-加强策略可诱导有效的 CD8 ⁺ T 细胞反应，并显着延长 B16-OVA 荷瘤小鼠的存活时间。更令人印象深刻的是，当使用 B16F10 裂解物代替 OVA 作为抗原时，通过使用 APN-CpG 观察到对 B16F10 肿瘤模型的显着抗肿瘤作用。这些结果表明 APNs 作为激活 CD8 ⁺ T 细胞反应的疫苗载体的巨大潜力以及纳米颗粒制剂中铝佐剂的光明前景。