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中国生物工程杂志

China Biotechnology
China Biotechnology
China Biotechnology  2018, Vol. 38 Issue (1): 51-56    DOI: 10.13523/j.cb.20180106
Orginal Article     
Advances in Research on Ebola Virus Vaccine: rVSV-ZEBOV
Yang-ling ZHANG,Yuan WANG,Ge ZHANG()
School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China
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Abstract  

Ebola viruses are the causative agents of Ebola hemorrhagic fever with high infection rates and high fatality rates, which were classified as category A pathogens. A safe and effective vaccine against Ebola virus infection is urgently needed. Currently, the Ebola virus vaccine candidates under study include viral vectors vaccines, protein vaccines and DNA vaccines. Among them, the most promising vaccine candidate is the recombinant vesicular stomatitis viral vector-based vaccine: rVSV-ZEBOV. The vaccine is safe and effective in prevention and treatment Ebola hemorrhagic fever. It is expected to be available in 2018. In order to gain an in-depth understanding of rVSV-ZEBOV vaccine, the preparation, pharmacological studies, and mechanism of action of rVSV-ZEBOV vaccine are focused on.

Key words： Ebola virus      rVSV-ZEBOV      Preparation      Pharmacological studies      Mechanism     
Received: 21 July 2017      Published: 31 January 2018
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Yang-ling ZHANG
Yuan WANG
Ge ZHANG
Cite this article:

Yang-ling ZHANG,Yuan WANG,Ge ZHANG. Advances in Research on Ebola Virus Vaccine: rVSV-ZEBOV. China Biotechnology, 2018, 38(1): 51-56.

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https://manu60.magtech.com.cn/biotech/10.13523/j.cb.20180106     OR     https://manu60.magtech.com.cn/biotech/Y2018/V38/I1/51

类型 疫苗举例
可复制病毒载体疫苗 重组水泡性口腔炎病毒载体疫苗,如rVSV-ZEBOV
重组人副流感病毒3型载体疫苗,如HPIV3-EBOVZ GP
重组巨细胞病毒载体疫苗
重组狂犬病病毒载体疫苗
复制缺陷型病毒载体疫苗 重组腺病毒载体疫苗,如ChAd3-EBOVZ、Ad26-ZEBOV、Ad5-EBOV
改良型痘苗病毒安卡拉株载体疫苗,如MVA-BN-Filo、MVA-EbolaZ
委内瑞拉马脑炎病毒复制子疫苗
库京病毒病毒样颗粒疫苗
亚单位疫苗 病毒样颗粒疫苗:Novavax
DNA疫苗 INO-4201、INO-4202、INO-4212、VRC-EBODNA023-00VP、VRCEBODNA012-00-VP、VRCMARDNA025-00-VP、
复制缺陷型病毒疫苗 rEBOVΔVP30
灭活疫苗 脂质体包裹的经γ射线灭活的EBO-Z
Table 1 The categories of Ebola virus vaccines
时间 试验分期 试验地点 试验对象 接种方式和剂量 参考文献
2005~2014年 临床前 — 小鼠、豚鼠、几内亚猪、食蟹猴、恒河猴等 单次免疫;口服给药、鼻腔给药、肌肉注射,暴露前给药、暴露后给药;均表现出较高的保护作用 [9,10]
2014年10月 临床I期 美国
WRAIR		 健康志愿者,39人 单次免疫;肌肉注射;剂量递增(3×106 PFU,2×107 PFU,1×108 PFU) [11]
NIAID 健康志愿者,39人 28天后加强免疫;肌肉注射;剂量递增(3×106 PFU,2×107 PFU,1×108 PFU) [11]
2014年11月 临床I期 德国 健康志愿者,20人 单次免疫;肌肉注射;剂量递增(3×106 PFU,2×107 PFU) [12]
加蓬 健康志愿者,100人 单次免疫;肌肉注射,剂量递增(3×105 PFU,3×106 PFU,3×105 PFU) [12,13]
肯尼亚 健康志愿者,100人 单次免疫;肌肉注射,剂量递增(3×106 PFU,2×107 PFU) [12]
瑞士 健康志愿者,115人 单次免疫;肌肉注射,剂量递增(1×107 PFU,5×107 PFU,3×105 PFU) [12,13]
2015年3月 临床II期 几内亚 前线医疗工作者,800~
1 200人		 试点阶段;单次免疫(2×107 PFU);肌肉注射 [14]
2015年4月 临床III期 几内亚 病毒暴露者,约10 000人 环围接种试验;单次免疫(2×107 PFU);肌肉注射 [14,15]
2015年4月 临床II/III期 塞拉利昂 超过8 650人 阶梯试验;单次免疫(2×107 PFU);肌肉注射 [16]
Table 2 The research status of Ebola virus vaccine: rVSV-ZEBOV
Fig.1 The gene structure of EBOV
Fig.2 The gene structure of VSV
 
Fig.4 The preparation process of rVSV-ZEBOV
Fig.5 The further attenuated modifications of vaccine based on VSV vector
[1]   Reynolds P, Marzi A . Ebola and Marburg virus vaccines. Virus Genes, 2017, 53(4): 501-515.
doi: 10.1007/s11262-017-1455-x pmid: 28447193
[2]   许黎黎, 张连峰 . 埃博拉出血热及埃博拉病毒的研究进展. 中国比较医学杂志, 2011, 21(1): 70-74.
doi: 10.3969/j.issn.1671-7856.2011.01.016
[2]   Xu L L, Zhang L F . Progress on Ebola hemorrhagic fever and Ebola viruses. Chinese Journal of Comparative Medicine, 2011, 21(1): 70-74.
doi: 10.3969/j.issn.1671-7856.2011.01.016
[3]   Wang Y, Li J, Hu Y , et al. Ebola vaccines in clinical trial: The promising candidates. Human Vaccines & Immunotherapeutics, 2017, 13(1): 153-168.
doi: 10.1080/21645515.2016.1225637 pmid: 27764560
[4]   Martins K A, Jahrling P B, Bavari S , et al. Ebola virus disease candidate vaccines under evaluation in clinical trials. Expert Review of Vaccines, 2016, 15(9): 1101-1112.
doi: 10.1080/14760584.2016.1187566 pmid: 27160784
[5]   Rao M, Bray M, Alving C R , et al. Induction of immune responses in mice and monkeys to Ebola Virus after immunization with liposome-encapsulated irradiated Ebola virus: Protection in Mice Requires CD4 + T Cells . Journal of Virology, 2002, 76(18): 9176.
doi: 10.1128/JVI.76.18.9176-9185.2002 pmid: 136452
[6]   Feldmann H, Jones S M , Daddario-DiCaprio K M, et al. Effective post-exposure treatment of Ebola infection. PLoS Pathogens, 2007, 3(1): e2.
doi: 10.1371/journal.ppat.0030002 pmid: 17238284
[7]   Jacobs M, Aarons E, Bhagani S , et al. Post-exposure prophylaxis against Ebola virus disease with experimental antiviral agents: a case-series of health-care workers. The Lancet Infectious Diseases, 2015, 15(11): 1300-1304.
doi: 10.1016/S1473-3099(15)00228-5 pmid: 26321189
[8]   WHO. Table of vaccine clinical trials.[ 2017-10-14]. Table of vaccine clinical trials. [2017-10-14].
[9]   Jones S M, Feldmann H, Str?her U , et al. Live attenuated recombinant vaccine protects nonhuman primates against Ebola and Marburg viruses. Nature Medicine, 2005, 11(7): 786-790.
doi: 10.1038/nm1258 pmid: 15937495
[10]   Qiu X, Fernando L, Alimonti J B , et al. Mucosal immunization of cynomolgus macaques with the VSVDeltaG/ZEBOVGP vaccine stimulates strong Ebola GP-specific immune responses. PLoS One, 2009, 4(5): e5547.
doi: 10.1371/journal.pone.0005547
[11]   Regules J A, Beigel J H, Paolino K M , et al. A recombinant vesicular stomatitis virus ebola vaccine. New England Journal of Medicine, 2017, 376(4): 330-341.
doi: 10.1056/NEJMoa1414216 pmid: 25830322
[12]   Agnandji S T, Huttner A, Zinser M E , et al. Phase 1 Trials of rVSV Ebola vaccine in Africa and Europe- Preliminary Report. New England Journal of Medicine, 2016, 374(17): 1647-1660.
doi: 10.1056/NEJMoa1502924
[13]   Medaglini D, Harandi A M, Ottenhoff T H , et al. Ebola vaccine R&D: Filling the knowledge gaps. Science Translational Medicine. 2015, 7(317): 317ps24-317ps24.
[14]   Henao-Restrepo A M, Longini I M, Egger M , et al. Efficacy and effectiveness of an rVSV-vectored vaccine expressing Ebola surface glycoprotein: interim results from the Guinea ring vaccination cluster-randomised trial. Lancet, 2015, 386(9996): 857-866.
doi: 10.1016/S0140-6736(15)61117-5 pmid: 26248676
[15]   Henao-Restrepo A M, Camacho A, Longini I M , et al. Efficacy and effectiveness of an rVSV-vectored vaccine in preventing Ebola virus disease: final results from the Guinea ring vaccination, open-label, cluster-randomised trial (Ebola ?a Suffit!). Lancet, 2016, 389(10068): 505-518.
[16]   Widdowson M A, Schrag S J, Carter R J , et al. Implementing an Ebola vaccine study-sierra leone. Mmwr Supplements, 2016, 65(3): 98.
doi: 10.15585/mmwr.su6503a14 pmid: 27387395
[17]   Rivera A, Messaoudi I . Molecular mechanisms of Ebola pathogenesis. Journal of Leukocyte Biology, 2016, 100(5): 889-904.
doi: 10.1189/jlb.4RI0316-099RR pmid: 27587404
[18]   Geisbert T W, Feldmann H . Recombinant vesicular stomatitis virus-based vaccines against Ebola and Marburg virus infections. The Journal of Infectious Diseases, 2011, 204(Suppl-3): S1075-1081.
doi: 10.1093/infdis/jir349 pmid: 3218670
[19]   Lawson N D, Stillman E A, Whitt M A , et al. Recombinant vesicular stomatitis viruses from DNA. Proceedings of the National Academy of Sciences of the United States of America, 1995, 92(10): 4477-4481.
doi: 10.1073/pnas.92.10.4477 pmid: 7753828
[20]   Schnell M J, Buonocore L, Whitt M A , et al. The minimal conserved transcription stop-start signal promotes stable expression of a foreign gene in vesicular stomatitis virus. Journal of Virology, 1996, 70(4): 2318-2323.
doi: 10.3109/13550289609146547 pmid: 8642658
[21]   Garbutt M, Liebscher R, Wahl-Jensen V , et al. Properties of replication-competent vesicular stomatitis virus vectors expressing glycoproteins of filoviruses and arenaviruses. Journal of Virology, 2004, 78(10): 5458-5465.
doi: 10.1128/JVI.78.10.5458-5465.2004 pmid: 15113924
[22]   Marzi A, Feldmann H, Geisbert T W , et al. Vesicular stomatitis virus-based vaccines for prophylaxis and treatment of filovirus infections. Journal of Bioterrorism & Biodefense, 2011, S1(4): 2157-2526-S1-004.
doi: 10.4172/2157-2526.S1-004 pmid: 3265573
[23]   Shuchman M . Ebola vaccine trial in west Africa faces criticism. Lancet, 2015, 385(9981): 1933-1934.
doi: 10.1016/S0140-6736(15)60938-2 pmid: 25979835
[24]   Mire C E, Matassov D, Geisbert J B , et al. Single-dose attenuated Vesiculovax vaccines protect primates against Ebola Makona virus. Nature, 2015, 520(7549): 688-691.
doi: 10.1038/nature14428 pmid: 25853476
[25]   Clarke D K, Nasar F, Lee M , et al. Synergistic attenuation of vesicular stomatitis virus by combination of specific G gene truncations and N gene translocations. Journal of Virology, 2007, 81(4): 2056-2064.
doi: 10.1128/JVI.01911-06
[26]   Marzi A, Engelmann F, Feldmann F , et al. Antibodies are necessary for rVSV/ZEBOV-GP-mediated protection against lethal Ebola virus challenge in nonhuman primates. Proceedings of the National Academy of Sciences of the United States of America, 2013, 110(5): 1893-1898.
doi: 10.1073/pnas.1209591110 pmid: 23319647
[27]   Menicucci A R, Sureshchandra S, Marzi A , et al. Transcriptomic analysis reveals a previously unknown role for CD8 +T-cells in rVSV-EBOV mediated protection . Scientific Reports, 2017, 7(1): 919.
doi: 10.1038/s41598-017-01032-8 pmid: 5430516
[28]   Farooq F, Beck K, Paolino K M , et al. Circulating follicular T helper cells and cytokine profle in humans following vaccination with the rVSV-ZEBOV Ebola vaccine. Scientific Reports, 2016, 6: 27944.
doi: 10.1038/srep27944 pmid: 4914957
[29]   Dahlke C, Kasonta R, Lunemann S , et al. Dose-dependent T-cell dynamics and cytokine cascade following rVSV-ZEBOV immunization. Ebiomedicine, 2017, 19: 107-118.
doi: 10.1016/j.ebiom.2017.03.045 pmid: 28434944
[30]   杨利敏, 李晶, 高福 , 等. 埃博拉病毒疫苗研究进展. 生物工程学报, 2015, 31(1): 1-23.
doi: 10.3760/cma.j.issn.1673-4211.2015.02.005
[30]   Yang L M, Li J, Gao F , et al. Overview of Ebola virus vaccine. Chinese Journal of Biotechnology, 2015, 31(1): 1-23.
doi: 10.3760/cma.j.issn.1673-4211.2015.02.005
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