Structure-based programming of lymph-node targeting in molecular vaccines.
Structure-based programming of lymph-node targeting in molecular vaccines.
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在癌症患者中，前哨淋巴结（LNs）的视觉识别是通过注射与内源性白蛋白紧密结合的染料来实现的，这些染料将这些化合物靶向到LNs，在那里它们被常驻的吞噬细胞有效地过滤。在这里，我们将这种“白蛋白搭便车”方法转化为分子疫苗，通过合成由抗原或佐剂货物组成的两亲体（amph-疫苗），通过促进溶解的极性聚合物链连接到亲脂性白蛋白结合尾部。经过结构优化的CpG-DNA/多肽amph-疫苗与其母体化合物相比，LN积累显著增加，全身传播减少，t细胞启动量增加30倍，抗肿瘤效果增强，同时大大降低全身毒性。amph疫苗提供了一种简单、广泛适用的策略，可以同时提高亚单位疫苗的效力和安全性。
In cancer patients, visual identification of sentinel lymph nodes (LNs) is achieved by the injection of dyes that bind avidly to endogenous albumin, targeting these compounds to LNs where they are efficiently filtered by resident phagocytes. Here we translate this “albumin hitchhiking” approach to molecular vaccines, via the synthesis of amphiphiles (amph-vaccines) comprised of an antigen or adjuvant cargo linked to a lipophilic albumin-binding tail by a solubility-promoting polar polymer chain. Structurally-optimized CpG-DNA/peptide amph-vaccines exhibited dramatic increases in LN accumulation and decreased systemic dissemination relative to their parent compounds, leading to 30-fold increases in T-cell priming and enhanced anti-tumor efficacy while greatly reducing systemic toxicity. Amph-vaccines provide a simple, broadly-applicable strategy to simultaneously increase the potency and safety of subunit vaccines.