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针对人乳头瘤病毒18型的嵌合候选疫苗的研发:概念验证

Development of chimeric candidate vaccine against HPV18: a proof of concept.

作者信息

Wahiduzzaman Mohammed, Sharma Chandresh, Dey Bindu, Bhatla Neerja, Singh Neeta

机构信息

Department of Biochemistry, All India Institute of Medical Sciences, Room No. 3027A, New Delhi, 110029, India,

出版信息

Immunol Res. 2015 Jun;62(2):189-97. doi: 10.1007/s12026-015-8650-4.

DOI:10.1007/s12026-015-8650-4
PMID:25929429
Abstract

Human papillomaviruses (HPVs) are prerequisite for the development of cervical cancer, with HPV16 and HPV18 being the most prevalent. Despite the fact that two prophylactic vaccines against HPVs are in the market, wide-scale application of the vaccine in developing countries is a major problem as far as cost of the vaccine and lack of therapeutic efficacy are concerned. Hence, the aim of our study was to develop HPV18 L1E7 chimeric virus-like particles (CVLPs) vaccine candidate possessing both, prophylactic and therapeutic potential against HPV18-associated cervical cancer. In this study, we have developed a potential candidate vaccine against HPV18 involving HPV18 L1E7 CVLPs, which was expressed in E. coli and assembled in vitro. These CVLPs were able to induce a neutralizing antibody response as well as a cell-mediated immune response in mice.

摘要

人乳头瘤病毒(HPV)是宫颈癌发生的必要条件,其中HPV16和HPV18最为常见。尽管市场上有两种针对HPV的预防性疫苗,但就疫苗成本和缺乏治疗效果而言,在发展中国家广泛应用该疫苗是一个主要问题。因此,我们研究的目的是开发一种具有预防和治疗HPV18相关宫颈癌潜力的HPV18 L1E7嵌合病毒样颗粒(CVLP)候选疫苗。在本研究中,我们开发了一种针对HPV18的潜在候选疫苗,该疫苗涉及在大肠杆菌中表达并在体外组装的HPV18 L1E7 CVLP。这些CVLP能够在小鼠体内诱导中和抗体反应以及细胞介导的免疫反应。

相似文献

1
Development of chimeric candidate vaccine against HPV18: a proof of concept.针对人乳头瘤病毒18型的嵌合候选疫苗的研发:概念验证
Immunol Res. 2015 Jun;62(2):189-97. doi: 10.1007/s12026-015-8650-4.
2
Human papillomavirus 16 L1-E7 chimeric virus like particles show prophylactic and therapeutic efficacy in murine model of cervical cancer.人乳头瘤病毒 16 L1-E7 嵌合病毒样颗粒在宫颈癌小鼠模型中显示出预防和治疗效果。
Vaccine. 2012 Aug 3;30(36):5417-24. doi: 10.1016/j.vaccine.2012.06.010. Epub 2012 Jun 17.
3
Characterization of an Escherichia coli-derived human papillomavirus type 16 and 18 bivalent vaccine.源自大肠杆菌的人乳头瘤病毒16型和18型二价疫苗的特性分析
Vaccine. 2017 Aug 16;35(35 Pt B):4637-4645. doi: 10.1016/j.vaccine.2017.06.084. Epub 2017 Jul 20.
4
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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Broad Cross-Protection Is Induced in Preclinical Models by a Human Papillomavirus Vaccine Composed of L1/L2 Chimeric Virus-Like Particles.由L1/L2嵌合病毒样颗粒组成的人乳头瘤病毒疫苗在临床前模型中诱导产生广泛的交叉保护作用。
J Virol. 2016 Jun 24;90(14):6314-25. doi: 10.1128/JVI.00449-16. Print 2016 Jul 15.
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Human papillomavirus L1 protein expressed in Escherichia coli self-assembles into virus-like particles that are highly immunogenic.人乳头瘤病毒 L1 蛋白在大肠杆菌中表达自我组装成具有高度免疫原性的病毒样颗粒。
Virus Res. 2016 Jul 15;220:97-103. doi: 10.1016/j.virusres.2016.04.017. Epub 2016 Apr 20.
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Displaying 31RG-1 peptide on the surface of HPV16 L1 by use of a human papillomavirus chimeric virus-like particle induces cross-neutralizing antibody responses in mice.利用人乳头瘤病毒嵌合病毒样颗粒在 HPV16 L1 表面展示 31RG-1 肽可诱导小鼠产生交叉中和抗体反应。
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[Construction of recombinant vaccinia virus expressing HPV18E7E6 fusion proteins and detection of its immunogenicity in mice].[表达人乳头瘤病毒18型E7E6融合蛋白重组痘苗病毒的构建及其在小鼠体内免疫原性的检测]
Zhonghua Shi Yan He Lin Chuang Bing Du Xue Za Zhi. 2008 Jun;22(3):189-91.
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Immunization with Human Papillomavirus 16 L1+E2 Chimeric Capsomers Elicits Cellular Immune Response and Antitumor Activity in a Mouse Model.用人乳头瘤病毒16型L1+E2嵌合衣壳蛋白进行免疫接种可在小鼠模型中引发细胞免疫反应和抗肿瘤活性。
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Developments in L2-based human papillomavirus (HPV) vaccines.基于第二代的人乳头瘤病毒(HPV)疫苗的进展。
Virus Res. 2017 Mar 2;231:166-175. doi: 10.1016/j.virusres.2016.11.020. Epub 2016 Nov 23.

本文引用的文献

1
A synthetic chimeric peptide harboring human papillomavirus 16 cytotoxic T lymphocyte epitopes shows therapeutic potential in a murine model of cervical cancer.一种包含人乳头瘤病毒16型细胞毒性T淋巴细胞表位的合成嵌合肽在宫颈癌小鼠模型中显示出治疗潜力。
Immunol Res. 2014 Jan;58(1):132-8. doi: 10.1007/s12026-013-8447-2.
2
Human papillomavirus 16 L1-E7 chimeric virus like particles show prophylactic and therapeutic efficacy in murine model of cervical cancer.人乳头瘤病毒 16 L1-E7 嵌合病毒样颗粒在宫颈癌小鼠模型中显示出预防和治疗效果。
Vaccine. 2012 Aug 3;30(36):5417-24. doi: 10.1016/j.vaccine.2012.06.010. Epub 2012 Jun 17.
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Sustained immunogenicity and efficacy of the HPV-16/18 AS04-adjuvanted vaccine: up to 8.4 years of follow-up.
HPV-16/18 AS04 佐剂疫苗的持续免疫原性和效力:长达 8.4 年的随访。
Hum Vaccin Immunother. 2012 Mar;8(3):390-7. doi: 10.4161/hv.18865. Epub 2012 Feb 13.
4
Classification of papillomaviruses (PVs) based on 189 PV types and proposal of taxonomic amendments.基于 189 种 HPV 型别对乳头瘤病毒(PVs)的分类以及分类学修订建议。
Virology. 2010 May 25;401(1):70-9. doi: 10.1016/j.virol.2010.02.002. Epub 2010 Mar 5.
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Therapeutic vaccines against human papillomavirus and cervical cancer.针对人乳头瘤病毒和宫颈癌的治疗性疫苗。
Open Virol J. 2009 Oct 23;3:67-83. doi: 10.2174/1874357900903010067.
6
Evaluation of quadrivalent HPV 6/11/16/18 vaccine efficacy against cervical and anogenital disease in subjects with serological evidence of prior vaccine type HPV infection.对有疫苗型人乳头瘤病毒(HPV)既往感染血清学证据的受试者进行四价HPV 6/11/16/18疫苗预防宫颈和肛门生殖器疾病疗效的评估。
Hum Vaccin. 2009 Oct;5(10):696-704. doi: 10.4161/hv.5.10.9515. Epub 2009 Oct 1.
7
A pooled analysis of continued prophylactic efficacy of quadrivalent human papillomavirus (Types 6/11/16/18) vaccine against high-grade cervical and external genital lesions.四价人乳头瘤病毒(6/11/16/18型)疫苗对高级别宫颈和外生殖器病变持续预防效果的汇总分析。
Cancer Prev Res (Phila). 2009 Oct;2(10):868-78. doi: 10.1158/1940-6207.CAPR-09-0031. Epub 2009 Sep 29.
8
Therapeutic HPV DNA vaccines.治疗性人乳头瘤病毒DNA疫苗
Expert Rev Vaccines. 2009 Sep;8(9):1221-35. doi: 10.1586/erv.09.76.
9
Chimeric L1-L2 virus-like particles as potential broad-spectrum human papillomavirus vaccines.嵌合L1-L2病毒样颗粒作为潜在的广谱人乳头瘤病毒疫苗。
J Virol. 2009 Oct;83(19):10085-95. doi: 10.1128/JVI.01088-09. Epub 2009 Jul 29.
10
HPV vaccination for the prevention of cervical intraepithelial neoplasia.人乳头瘤病毒疫苗预防宫颈上皮内瘤变
N Engl J Med. 2009 Jul 16;361(3):271-8. doi: 10.1056/NEJMct0806938.