携带CCL19、IL-2和hpv16e7的病毒样颗粒在HLA-A2转基因小鼠中引发保护性T细胞反应

The Open Virology Journal Pub Date : 2012-01-01 Epub Date: 2012-12-28 DOI:10.2174/1874357901206010270
Victoria Juarez, H Amalia Pasolli, Andrea Hellwig, Natalio Garbi, Angel Cid Arregui
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引用次数: 20

摘要

高危基因型人乳头瘤病毒(hr - hpv)感染是子宫颈癌的原因。尽管针对两种最流行的人乳头瘤病毒类型(HPV16和18)的预防性疫苗最近已经商业化,但仍需要针对人乳头瘤病毒的有效治疗性疫苗。我们在小鼠中测试了一种由乙型肝炎小表面抗原(HBsAg(S))组成的嵌合蛋白,该嵌合蛋白在其n端由趋化因子CC配体19/巨噬细胞炎症蛋白3β (CCL19/MIP-3β)组成,在其c端由白细胞介素2 (IL-2)和人工hpv16e7多肽组成。这种蛋白质被组装成纳米颗粒,CCL19和IL-2都保留了它们的功能。用编码该蛋白的质粒免疫的HLA-A2 (AAD)转基因小鼠在不需要佐剂的情况下对E7产生特异性T细胞反应。此外,在植入表达E6/ e7的TC-1/A2肿瘤细胞系后,接种疫苗可以阻止肿瘤的发展。我们的研究结果表明,基于携带短E7表位和免疫刺激结构域的HBsAg(S)纳米颗粒的疫苗可能在治疗由hr - hpv引起的宫颈癌前病变或癌症病变的患者中具有治疗价值。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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Virus-Like Particles Harboring CCL19, IL-2 and HPV16 E7 Elicit Protective T Cell Responses in HLA-A2 Transgenic Mice.

Infection by high-risk genotypes of human papillomaviruses (HR-HPVs) is the cause of cancer of the uterine cervix. Although prophylactic vaccines directed against the two most prevalent HR-HPV types (HPV16 and 18) have been commercialized recently, there is a need for effective therapeutic vaccines against HR-HPVs. We have tested in mice a chimeric protein composed of the hepatitis B small surface antigen (HBsAg(S)) flanked at its N-terminus by chemokine CC ligand 19/macrophage inflammatory protein-3β (CCL19/MIP-3β), and at the C-terminus by interleukin 2 (IL-2) and an artificial HPV16 E7 polytope. This protein is assembled into nanoparticles and both CCL19 and IL-2 conserve their functionality. HLA-A2 (AAD) transgenic mice immunized with a plasmid encoding this protein mounted specific T cell responses against E7 without the need of an adjuvant. Furthermore, vaccination prevented the development of tumors after implantation of the E6/E7-expressing TC-1/A2 tumor cell line. Our results suggest that vaccines based on HBsAg(S) nanoparticles carrying short E7 epitopes and immune-stimulatory domains might be of therapeutic value in the treatment of patients suffering from cervical pre-cancer or cancer lesions caused by HR-HPVs.

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