DNA vaccinations are promising strategies for treating diseases that require cellular immunity (i.e., cancer and protozoan infection). Here, we report on the use of a liposomal nanocarrier (lipid nanoparticles (LNPs)) composed of an SS-cleavable and pH-activated lipidlike material (ssPalm) as an in vivo DNA vaccine. After subcutaneous administration, the LNPs containing an ssPalmE, an ssPalm with vitamin E scaffolds, elicited a higher gene expression activity in comparison with the other LNPs composed of the ssPalms with different hydrophobic scaffolds. Immunization with the ssPalmE-LNPs encapsulating plasmid DNA that encodes ovalbumin (OVA, a model tumor antigen) or profilin (TgPF, a potent antigen of Toxoplasma gondii) induced substantial antitumor or antiprotozoan effects, respectively. Flow cytometry analysis of the cells that had taken up the LNPs in draining lymph nodes (dLNs) showed that the ssPalmE-LNPs were largely taken up by macrophages and a small number of dendritic cells. We found that the transient deletion of CD169+ macrophages, a subpopulation of macrophages that play a key role in cancer immunity, unexpectedly enhanced the activity of the DNA vaccine. These data suggest that the ssPalmE-LNPs are effective DNA vaccine carriers, and a strategy for avoiding their being trapped by CD169+ macrophages will be a promising approach for developing next-generation DNA vaccines.

中文翻译：

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pH响应脂质纳米颗粒的维生素E支架作为癌症和原生动物感染中的DNA疫苗。

DNA疫苗是治疗需要细胞免疫的疾病（例如，癌症和原生动物感染）的有前途的策略。在这里，我们报告使用脂质体纳米载体（脂质纳米颗粒（LNPs））作为体内DNA疫苗的用途，脂质体纳米载体是由SS可裂解和pH活化的类脂质材料（ssPalm）组成。皮下给药后，与由具有不同疏水性支架的ssPalms组成的其他LNP相比，包含ssPalmE，具有维生素E支架的ssPalm的LNP引起更高的基因表达活性。ssPalmE-LNPs封装的质粒DNA分别编码卵白蛋白（OVA，模型肿瘤抗原）或蛋白原素（TgPF，弓形虫的有效抗原）进行免疫，分别诱导了显着的抗肿瘤或原生动物作用。对引流淋巴结（dLNs）中已摄取LNP的细胞进行流式细胞术分析表明，ssPalmE-LNPs被巨噬细胞和少量树突状细胞摄取。我们发现，CD169 +巨噬细胞（在癌症免疫中起关键作用的巨噬细胞亚群）的瞬时缺失出乎意料地增强了DNA疫苗的活性。这些数据表明，ssPalmE-LNP是有效的DNA疫苗携带者，一种避免其被CD169 +巨噬细胞捕获的策略将是开发下一代DNA疫苗的有前途的方法。在癌症免疫中起关键作用的巨噬细胞亚群出乎意料地增强了DNA疫苗的活性。这些数据表明，ssPalmE-LNP是有效的DNA疫苗携带者，一种避免其被CD169 +巨噬细胞捕获的策略将是开发下一代DNA疫苗的有前途的方法。在癌症免疫中起关键作用的巨噬细胞亚群，意外地增强了DNA疫苗的活性。这些数据表明，ssPalmE-LNP是有效的DNA疫苗携带者，一种避免其被CD169 +巨噬细胞捕获的策略将是开发下一代DNA疫苗的有前途的方法。