A novel self-assembled nanoparticle vaccine with HIV-1 Tat₄₉₋₅₇/HPV16 E7₄₉₋₅₇ fusion peptide and GM-CSF DNA elicits potent and prolonged CD8⁺ T cell-dependent anti-tumor immunity in mice.
A novel self-assembled nanoparticle vaccine with HIV-1 Tat₄₉₋₅₇/HPV16 E7₄₉₋₅₇ fusion peptide and GM-CSF DNA elicits potent and prolonged CD8⁺ T cell-dependent anti-tumor immunity in mice.
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DOI：
10.1016/j.vaccine.2011.12.029
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发表时间：
2012-02
期刊：
影响因子：
5.5
通讯作者：
Jun Tang;R. Yin;Yi Tian;Zemin Huang;Jinglei Shi;Xiao-lan Fu;Li Wang;Yuzhang Wu;F. Hao;B. Ni
中科院分区：
文献类型：
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作者：
Jun Tang;R. Yin;Yi Tian;Zemin Huang;Jinglei Shi;Xiao-lan Fu;Li Wang;Yuzhang Wu;F. Hao;B. Ni
从人乳头瘤病毒（HPV） 16型E7蛋白衍生的肽基疫苗被开发出来，用于诱导有效的T细胞应答，以对抗已建立的宫颈癌，但临床成功有限。有必要开发新的基于肽的策略来大幅提高对hpv16相关癌症的免疫反应。本研究旨在结合HPV16 e749 -57细胞毒性T淋巴细胞（CTL）表位和粒细胞-巨噬细胞集落刺激因子（GM-CSF）基因融合的细胞穿透肽HIV-1 tat49 -57，设计一种新的基于多肽的自组装纳米颗粒HPV16疫苗，并研究其如何改善免疫应答和体内外治疗效果。制备了纳米颗粒，并通过透射电镜（TEM）、凝胶阻滞和dna酶I保护实验对其进行了鉴定。这种疫苗制剂形成了20-80nm的纳米颗粒，大大提高了体外和体内的表位特异性免疫。重要的是，在预防性和治疗性小鼠模型中，这种疫苗类型与肿瘤生长减少和长期生存率提高有关。潜在的机制被确定为涉及启动CD8+记忆T亚型细胞频率的增强。这些结果表明，纳米颗粒Tat-E7/pGM-CSF代表了一种有希望的新方法来增强基于肽的宫颈癌疫苗的效力，这种疫苗设计策略可能为病毒相关疾病和特异性肿瘤免疫治疗的研究提供有用的参考。
Peptide-based vaccines derived from the E7 protein of human papillomavirus (HPV) type 16 were developed to induce effective T cell responses against established cervical cancer, but have met with limited clinical success. It is necessary to develop novel peptide-based strategies to substantially improve the immune response against HPV16-related cancer. In this study, we aimed to design a novel peptide-based self-assembled nanoparticle HPV16 vaccine by combining the cell-penetrating peptide HIV-1 Tat49-57that was fused with the HPV16 E749-57cytotoxic T lymphocyte (CTL) epitope and the granulocyte-macrophage colony stimulating factor (GM-CSF) gene, and to investigate how it improves the immune response and the therapeutic outcome ex vivo and in vivo. Nanoparticles were prepared and identified by transmission electron microscopy (TEM), gel retardation and DNase I protection assays. This type of vaccine formulation formed the 20–80nm nanoparticles, and greatly improved epitope-specific immunity both ex vivo and in vivo. Importantly, this vaccine type was associated with decreased tumor growth and enhanced long-term survival in the prophylactic and therapeutic mouse models. The underlying mechanisms were determined to involve priming of enhanced frequency of CD8+memory T subtype cells. These results suggest that the nanoparticle Tat-E7/pGM-CSF represents a promising novel approach to enhance the potency of peptide-based cervical cancer vaccines, and this vaccine design strategy may act as a useful reference for research of virus-associated diseases and specific tumor immunotherapies.