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生成马痘病毒载体疫苗候选物并在动物模型中进行测试。

Generating MVA-Vector Vaccine Candidates and Testing Them in Animal Models.

作者信息

Tscherne Alina, Meyer Zu Natrup Christian, Kalodimou Georgia, Volz Asisa

机构信息

Division of Virology, Department of Veterinary Science, LMU Munich, Oberschleißheim, Germany.

Institute of Virology, University of Veterinary Medicine Hannover, Hannover, Germany.

出版信息

Methods Mol Biol. 2025;2860:297-340. doi: 10.1007/978-1-0716-4160-6_20.

DOI:10.1007/978-1-0716-4160-6_20
PMID:39621276
Abstract

Modified Vaccinia Virus Ankara (MVA) is a highly attenuated and replication-deficient vaccinia virus developed through serial passages in chicken embryo fibroblasts (CEF). MVA is increasingly used in biomedicine for vaccine development in preclinical and clinical studies in humans. Major benefits of MVA include a well-established record in clinical safety, long-standing experience in genetic engineering of the virus, a large data set demonstrating efficacy in preclinical models with the capacity to induce both protective antigen-specific antibody and cellular immune responses, and the availability of virus production under Good Manufacturing Practice (GMP) suitable for industrial scale amplification. In this chapter, we describe established state-of-the-art protocols for generating, amplifying, and purifying recombinant MVA viruses, including possible vector viruses for further investigations as well as clinical evaluation.

摘要

安卡拉痘苗病毒(MVA)是一种高度减毒且复制缺陷的痘苗病毒,通过在鸡胚成纤维细胞(CEF)中连续传代培养而成。MVA在生物医学领域越来越多地用于人类临床前和临床研究中的疫苗开发。MVA的主要优势包括临床安全性方面有充分的记录、在病毒基因工程方面有长期经验、大量数据集表明其在临床前模型中具有诱导保护性抗原特异性抗体和细胞免疫反应的功效,以及具备符合药品生产质量管理规范(GMP)的病毒生产条件,适合进行工业规模扩增。在本章中,我们描述了用于产生、扩增和纯化重组MVA病毒的成熟的先进方案,包括可用于进一步研究及临床评估的可能载体病毒。

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1
Generating MVA-Vector Vaccine Candidates and Testing Them in Animal Models.生成马痘病毒载体疫苗候选物并在动物模型中进行测试。
Methods Mol Biol. 2025;2860:297-340. doi: 10.1007/978-1-0716-4160-6_20.
2
Expanding the repertoire of Modified Vaccinia Ankara-based vaccine vectors via genetic complementation strategies.通过基因互补策略扩大基于安卡拉痘苗病毒的改良疫苗载体的种类。
PLoS One. 2009;4(5):e5445. doi: 10.1371/journal.pone.0005445. Epub 2009 May 6.
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[Modified vaccinia virus ankara (MVA)--development as recombinant vaccine and prospects for use in veterinary medicine].[安卡拉改良痘苗病毒(MVA)——作为重组疫苗的研发及在兽医学中的应用前景]
Berl Munch Tierarztl Wochenschr. 2015 Nov-Dec;128(11-12):464-72.
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Easy and efficient protocols for working with recombinant vaccinia virus MVA.用于处理重组痘苗病毒MVA的简便高效方案。
Methods Mol Biol. 2012;890:59-92. doi: 10.1007/978-1-61779-876-4_4.
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Modified Vaccinia Virus Ankara: History, Value in Basic Research, and Current Perspectives for Vaccine Development.安卡拉改良牛痘病毒:历史、基础研究价值及疫苗开发的当前展望
Adv Virus Res. 2017;97:187-243. doi: 10.1016/bs.aivir.2016.07.001. Epub 2016 Aug 1.
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Vaccinia vectors as candidate vaccines: the development of modified vaccinia virus Ankara for antigen delivery.痘苗病毒载体作为候选疫苗:用于抗原递送的改良安卡拉痘苗病毒的研发。
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Poxviral promoters for improving the immunogenicity of MVA delivered vaccines.痘病毒启动子增强 MVA 传递疫苗的免疫原性。
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Generation and Production of Modified Vaccinia Virus Ankara (MVA) as a Vaccine Vector.作为疫苗载体的改良安卡拉痘苗病毒(MVA)的产生与生产。
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Replication of modified vaccinia virus Ankara in primary chicken embryo fibroblasts requires expression of the interferon resistance gene E3L.改良安卡拉痘苗病毒在原代鸡胚成纤维细胞中的复制需要干扰素抗性基因E3L的表达。
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Percutaneous Vaccination as an Effective Method of Delivery of MVA and MVA-Vectored Vaccines.经皮接种作为痘苗病毒安卡拉株(MVA)及MVA载体疫苗的一种有效递送方法
PLoS One. 2016 Feb 19;11(2):e0149364. doi: 10.1371/journal.pone.0149364. eCollection 2016.

本文引用的文献

1
Immunity to Tick-Borne Encephalitis Virus NS3 Protein Induced with a Recombinant Modified Vaccinia Virus Ankara Fails to Afford Mice Protection against TBEV Infection.用重组改良安卡拉痘病毒诱导产生的对蜱传脑炎病毒NS3蛋白的免疫未能使小鼠免受蜱传脑炎病毒感染。
Vaccines (Basel). 2024 Jan 20;12(1):105. doi: 10.3390/vaccines12010105.
2
Newly Designed Poxviral Promoters to Improve Immunogenicity and Efficacy of MVA-NP Candidate Vaccines against Lethal Influenza Virus Infection in Mice.新设计的痘病毒启动子可提高MVA-NP候选疫苗对小鼠致命性流感病毒感染的免疫原性和效力。
Pathogens. 2023 Jun 23;12(7):867. doi: 10.3390/pathogens12070867.
3
A recombinant Modified Vaccinia virus Ankara expressing prME of tick-borne encephalitis virus affords mice full protection against TBEV infection.
一种表达蜱传脑炎病毒 prME 的重组改良安卡拉牛痘病毒能为小鼠提供针对 TBEV 感染的完全保护。
Front Immunol. 2023 Apr 21;14:1182963. doi: 10.3389/fimmu.2023.1182963. eCollection 2023.
4
Stabilized recombinant SARS-CoV-2 spike antigen enhances vaccine immunogenicity and protective capacity.稳定的重组 SARS-CoV-2 刺突抗原增强了疫苗的免疫原性和保护能力。
J Clin Invest. 2022 Dec 15;132(24):e159895. doi: 10.1172/JCI159895.
5
Increased neutralization and IgG epitope identification after MVA-MERS-S booster vaccination against Middle East respiratory syndrome.MVA-MERS-S 加强疫苗接种后对中东呼吸综合征的中和作用增强和 IgG 表位鉴定。
Nat Commun. 2022 Jul 19;13(1):4182. doi: 10.1038/s41467-022-31557-0.
6
Protective CD8+ T Cell Response Induced by Modified Vaccinia Virus Ankara Delivering Ebola Virus Nucleoprotein.由安卡拉痘苗病毒携带埃博拉病毒核蛋白诱导的保护性CD8 + T细胞反应。
Vaccines (Basel). 2022 Mar 29;10(4):533. doi: 10.3390/vaccines10040533.
7
Immunogenicity and efficacy of the COVID-19 candidate vector vaccine MVA-SARS-2-S in preclinical vaccination.新型冠状病毒候选载体疫苗 MVA-SARS-2-S 的免疫原性和疗效的临床前疫苗接种研究。
Proc Natl Acad Sci U S A. 2021 Jul 13;118(28). doi: 10.1073/pnas.2026207118.
8
Safety and immunogenicity of a modified vaccinia virus Ankara vector vaccine candidate for Middle East respiratory syndrome: an open-label, phase 1 trial.一种用于中东呼吸综合征的改良安卡拉痘苗病毒载体候选疫苗的安全性和免疫原性:一项开放性、1 期临床试验。
Lancet Infect Dis. 2020 Jul;20(7):827-838. doi: 10.1016/S1473-3099(20)30248-6. Epub 2020 Apr 21.
9
CRISPR/Cas9-Advancing Orthopoxvirus Genome Editing for Vaccine and Vector Development.CRISPR/Cas9-推动正痘病毒基因组编辑用于疫苗和载体开发。
Viruses. 2018 Jan 22;10(1):50. doi: 10.3390/v10010050.
10
Modified Vaccinia Virus Ankara: History, Value in Basic Research, and Current Perspectives for Vaccine Development.安卡拉改良牛痘病毒:历史、基础研究价值及疫苗开发的当前展望
Adv Virus Res. 2017;97:187-243. doi: 10.1016/bs.aivir.2016.07.001. Epub 2016 Aug 1.