"Minimalist" Nanovaccine Constituted from Near Whole Antigen for Cancer Immunotherapy
"Minimalist" Nanovaccine Constituted from Near Whole Antigen for Cancer Immunotherapy
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由近乎完整的抗原构成的“极简”纳米疫苗用于癌症免疫治疗
DOI：
10.1021/acsnano.8b00558
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发表时间：
2018-07-01
期刊：
影响因子：
17.1
通讯作者：
Li, Yongyong
中科院分区：
文献类型：
--
作者：
Wang, Kun;Wen, Shuman;Li, Yongyong
疫苗设计的主要挑战之一是过度依赖于大量佐剂的掺入，这实际上违反了“极简”原则。在本研究中，开发了一种由几乎全抗原（高达97% wt %）衍生的紧凑纳米疫苗。每个抗原（卵清蛋白，OVA）内的游离半胱氨酸稳定了纳米疫苗的结构，这些抗原在时间空间上暴露并热驱动形成广泛的分子间二硫网络。这一过程使得在合成过程中将危险信号（CpG-SH）整合到网络中来设计纳米疫苗成为可能。研制出50纳米大小的纳米疫苗，每纳米颗粒包含约500个抗原分子。纳米疫苗可预防70%的小鼠B16-OVA黑色素瘤的发生（对照组为0%）。强烈的纳米疫苗诱导的细胞毒性T淋巴细胞实现了显著的肿瘤抑制。这一策略可适用于未来临床环境中最少成分的疫苗设计。
One of the major challenges in vaccine design has been the over dependence on incorporation of abundant adjuvants, which in fact is in violation of the "minimalist" principle. In the present study, a compact nanovaccine derived from a near whole antigen (up to 97 wt %) was developed. The nanovaccine structure was stabilized by free cysteines within each antigen (ovalbumin, OVA), which were tempospatially exposed and heat-driven to form an extensive intermolecular disulfide network. This process enables the engineering of a nanovaccine upon integration of the danger signal (CpG-SH) into the network during the synthetic process. The 50 nm-sized nanovaccine was developed comprising approximately 500 antigen molecules per nanoparticle. The nano vaccine prophylactically protected 70% of mice from tumorigenesis (0% for the control group) in murine B16-OVA melanoma. Significant tumor inhibition was achieved by strongly nanovaccine-induced cytotoxic T lymphocytes. This strategy can be adapted for the future design of vaccine for a minimalist composition in clinical settings.