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首页> 外文期刊>Vaccine >An improved rearranged Human Papillomavirus Type 16 E7 DNA vaccine candidate (HPV-16 E7SH) induces an E7 wildtype-specific T cell response
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An improved rearranged Human Papillomavirus Type 16 E7 DNA vaccine candidate (HPV-16 E7SH) induces an E7 wildtype-specific T cell response

机译：改进的重排人乳头瘤病毒16型E7 DNA候选疫苗（HPV-16 E7SH）诱导E7野生型特异性T细胞反应

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A new and very promising approach in vaccine development is the application of naked DNA. In comparison to conventional vaccines it offers several advantages, especially if there is a need for the development of low cost vaccines. Infection with high-risk human papillomaviruses (hr-HPVs) is the major risk factor for the development of cervical cancer (cc), the third most common cancer in women worldwide. The HPV E7 oncogene is constitutively expressed in HPV-infected cells and represents an excellent target for immune therapy of HPV-related disease. Therefore, we chose the HPV-16 E7 as model antigen in the development of a therapeutic DNA vaccine candidate. For safety reasons the use of a transforming gene like the HPV-16 E7 for DNA vaccination is not feasible in humans. In consequence we have generated an artificial ("shuffled") HPV-16 E7-gene (HPV-16 E7SH), containing all putative cytotoxic T-lymphocyte (CTLs) epitopes and exhibiting high safety features. Here, we show the induction of a strong E7-wildtype (E7WT) directed cellular and humoral immune response including tumor protection and regression after in vivo immunization in the murine system. Moreover, the vaccine candidate demonstrated immunogenicity in humans, demonstrated by priming of antigen-specific T cells in vitro. Importantly, the artificial HPV-gene has completely lost its transforming properties as measured in soft agar transformation assays. These results may be of importance for the development of vaccines based on oncogenes or oncoproteins.
机译：裸露DNA的应用是疫苗开发中一种非常有希望的新方法。与常规疫苗相比，它具有几个优点，尤其是在需要开发低成本疫苗的情况下。高危人类乳头瘤病毒（hr-HPVs）感染是宫颈癌（cc）发展的主要危险因素，宫颈癌是全球女性中第三大最常见的癌症。 HPV E7癌基因在HPV感染的细胞中组成性表达，是HPV相关疾病免疫治疗的极佳靶标。因此，我们在开发治疗性DNA疫苗候选药物时选择了HPV-16 E7作为模型抗原。出于安全原因，在人类中无法使用像HPV-16 E7这样的转化基因进行DNA疫苗接种。结果，我们产生了人工的（“改组”的）HPV-16 E7基因（HPV-16 E7SH），其中包含所有假定的细胞毒性T淋巴细胞（CTL）表位，并显示出高安全性。在这里，我们显示了在小鼠系统中进行体内免疫后，诱导了强烈的E7野生型（E7WT）定向的细胞和体液免疫应答，包括肿瘤保护和消退。此外，候选疫苗在人体中表现出免疫原性，这是通过在体外引发抗原特异性T细胞而证明的。重要的是，如在软琼脂转化试验中所测量的，人工HPV基因已经完全丧失了其转化特性。这些结果对于开发基于癌基因或癌蛋白的疫苗可能具有重要意义。

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