We have previously demonstrated the immunogenicity of VGX-3100, a multicomponent DNA immunotherapy for the treatment of Human Papillomavirus (HPV)16/18-positive CIN2/3 in a phase 1 clinical trial. Here, we report on the ability to boost immune responses with an additional dose of VGX-3100. Patients completing our initial phase 1 trial were offered enrollment into a follow on trial consisting of a single boost dose of VGX-3100. Data show both cellular and humoral immune responses could be augmented above pre-boost levels, including the induction of interferon (IFN)γ production, tumor necrosis factor (TNF)α production, CD8+ T cell activation and the synthesis of lytic proteins. Moreover, observation of antigen-specific regulation of immune-related gene transcripts suggests the induction of a proinflammatory response following the boost. Analysis of T cell receptor (TCR) sequencing suggests the localization of putative HPV-specific T cell clones to the cervical mucosa, which underscores the putative mechanism of action of lesion regression and HPV16/18 elimination noted in our double-blind placebo-controlled phase 2B trial. Taken together, these data indicate that VGX-3100 drives the induction of robust cellular and humoral immune responses that can be augmented by a fourth "booster" dose. These data could be important in the scope of increasing the clinical efficacy rate of VGX-3100.

中文翻译：

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VGX-3100增强了对HPV16和HPV18 E6和E7抗原的细胞和体液免疫反应。

我们先前已经在1期临床试验中证明了VGX-3100的免疫原性，VGX-3100是用于治疗人乳头瘤病毒（HPV）16/18阳性CIN2 / 3的多组分DNA免疫疗法。在这里，我们报告了使用额外剂量的VGX-3100增强免疫反应的能力。为完成我们最初的1期试验的患者提供了入组包括单次加强剂量VGX-3100的试验的随访。数据显示，细胞免疫和体液免疫反应均可增强至增强前水平以上，包括诱导干扰素（IFN）γ的产生，肿瘤坏死因子（TNF）α的产生，CD8 + T细胞的活化以及裂解蛋白的合成。此外，对免疫相关基因转录本的抗原特异性调节的观察表明，加强免疫后诱导了促炎反应。T细胞受体（TCR）测序分析表明，可能的HPV特异性T细胞克隆位于宫颈粘膜，这强调了在双盲安慰剂对照阶段中发现的病灶消退和HPV16 / 18消除的推定作用机制2B试用。综上所述，这些数据表明VGX-3100诱导了强烈的细胞和体液免疫反应的诱导，可以通过第四次“加强”剂量来增强这种免疫反应。这些数据对于提高VGX-3100的临床疗效率可能是重要的。综上所述，这些数据表明VGX-3100诱导了强烈的细胞和体液免疫反应的诱导，可以通过第四次“加强”剂量来增强这种免疫反应。这些数据对于提高VGX-3100的临床疗效率可能是重要的。综上所述，这些数据表明VGX-3100诱导了强烈的细胞和体液免疫反应的诱导，可以通过第四次“加强”剂量来增强这种免疫反应。这些数据对于提高VGX-3100的临床疗效率可能是重要的。