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用含有 HPV-16 E6 和 E7 表位的 HPV-16 L1 嵌合病毒样颗粒免疫可在 HPV-16 肿瘤小鼠模型中产生持久的预防和治疗效果。

Immunization with an HPV-16 L1-based chimeric virus-like particle containing HPV-16 E6 and E7 epitopes elicits long-lasting prophylactic and therapeutic efficacy in an HPV-16 tumor mice model.

机构信息

Unidad de Investigación Médica en Enfermedades Oncológicas, IMSS, CMN SXXI, Mexico, D.F., Mexico.

出版信息

Arch Virol. 2014 Feb;159(2):291-305. doi: 10.1007/s00705-013-1819-z. Epub 2013 Aug 29.

DOI:10.1007/s00705-013-1819-z
PMID:23990055
Abstract

HPV L1-based virus-like particles vaccines (VLPs) efficiently induce temporary prophylactic activity through the induction of neutralizing antibodies; however, VLPs that can provide prophylactic as well as therapeutic properties for longer periods of time are needed. For this purpose, we generated a novel HPV 16 L1-based chimeric virus-like particle (cVLP) produced in plants that contains a string of T-cell epitopes from HPV 16 E6 and E7 fused to its C-terminus. In the present study, we analyzed the persistence of specific IgG antibodies with neutralizing activity induced by immunization with these cVLPs, as well as their therapeutic potential in a tumor model of C57BL/6 mice. We observed that these cVLPs induced persistent IgG antibodies for over 12 months, with reactivity and neutralizing activity for VLPs composed of only the HPV-16 L1 protein. Efficient protection for long periods of time and inhibition of tumor growth induced by TC-1 tumor cells expressing HPV-16 E6/E7 oncoproteins, as well as significant tumor reduction (57 %), were observed in mice immunized with these cVLPs. Finally, we discuss the possibility that chimeric particles of the type described in this work may be the basis for developing HPV prophylactic and therapeutic vaccines with high efficacy.

摘要

HPV L1 基于的病毒样颗粒疫苗 (VLPs) 通过诱导中和抗体有效地诱导临时预防活性; 然而,需要能够提供更长时间的预防和治疗特性的 VLPs。为此,我们在植物中生成了一种新型的 HPV 16 L1 基于嵌合病毒样颗粒 (cVLP),其包含 HPV 16 E6 和 E7 的 T 细胞表位串融合到其 C 末端。在本研究中,我们分析了用这些 cVLPs 免疫诱导的具有中和活性的特异性 IgG 抗体的持久性,以及它们在 C57BL/6 小鼠肿瘤模型中的治疗潜力。我们观察到,这些 cVLPs 诱导了超过 12 个月的持续 IgG 抗体,对仅由 HPV-16 L1 蛋白组成的 VLPs 具有反应性和中和活性。用这些 cVLPs 免疫的小鼠观察到对长时间的有效保护和对表达 HPV-16 E6/E7 癌蛋白的 TC-1 肿瘤细胞的肿瘤生长的抑制,以及显著的肿瘤减少 (57%)。最后,我们讨论了这种类型的嵌合颗粒可能成为开发具有高效性的 HPV 预防性和治疗性疫苗的基础的可能性。

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Immunization with an HPV-16 L1-based chimeric virus-like particle containing HPV-16 E6 and E7 epitopes elicits long-lasting prophylactic and therapeutic efficacy in an HPV-16 tumor mice model.用含有 HPV-16 E6 和 E7 表位的 HPV-16 L1 嵌合病毒样颗粒免疫可在 HPV-16 肿瘤小鼠模型中产生持久的预防和治疗效果。
Arch Virol. 2014 Feb;159(2):291-305. doi: 10.1007/s00705-013-1819-z. Epub 2013 Aug 29.
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An HPV 16 L1-based chimeric human papilloma virus-like particles containing a string of epitopes produced in plants is able to elicit humoral and cytotoxic T-cell activity in mice.一种基于人乳头瘤病毒16型L1的嵌合人乳头瘤病毒样颗粒,其包含一串在植物中产生的表位,能够在小鼠中引发体液免疫和细胞毒性T细胞活性。
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A novel HPV 16 L1-based chimeric virus-like particle containing E6 and E7 seroreactive epitopes permits highly specific detection of antibodies in patients with CIN 1 and HPV-16 infection.一种新型 HPV 16 L1 嵌合病毒样颗粒,包含 E6 和 E7 血清反应性表位,可高度特异性检测 CIN 1 和 HPV-16 感染患者的抗体。
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