|本期目录/Table of Contents|

[1]张 哲,侯利华.埃博拉疫苗临床试验研究进展[J].传染病信息,2018,05:430-435.
 ZHANG Zhe,HOU Li-hua*.Advances in clinical trials of Ebola vaccine[J].Infectious Disease Information,2018,05:430-435.





Advances in clinical trials of Ebola vaccine
张 哲侯利华
100071 北京,军事科学院军事医学研究院生物 工程研究所(张哲、侯利华)
ZHANG Zhe HOU Li-hua*
Institute of Biotechnology, Academy of Military Medical Sciences, Beijing 100071, China
 Ebola vaccine viral vector vaccine clinical trial rVSV-ZEBOV
 埃博拉病毒病是一种由埃博拉病毒引发的高致命率的出血热疾病。近些年大规模暴发的埃博拉疫情引起了全 世界的重点关注。目前,已有多种类型的埃博拉疫苗进入临床试验阶段。病毒载体疫苗因其免疫应答快、水平高的特点使人 印象深刻。其中,重组水疱性口炎病毒载体埃博拉疫苗(rVSV-ZEBOV)率先在几内亚III 期临床试验中证明了其出色的保 护效果。本文将阐述现阶段已经开展临床试验的埃博拉疫苗,并围绕安全性、免疫原性等方面对rVSV-ZEBOV 进行重点介绍。 
 Ebola virus disease (EVD) is a high fatality hemorrhagic fever disease caused by Ebola virus. Worldwide attention has been attracted due to the large-scale Ebola outbreak in recent years. Currently, many types of Ebola vaccines have been evaluated in the clinical trials. Viral vector vaccines are impressive owing to its fast and high-level immune response. Among them, recombinant vesicular stomatitis virus-based vaccine expressing Zaire Ebola virus glycoprotein (rVSV-ZEBOV) has showed a significant protection against EVD in a phase Ⅲ clinical trial in Guinea. This paper aims to review Ebola vaccines in the undergoing clinical trials and focus on rVSV-ZEBOV in terms of safety and immunogenicity.       


[1] Towner JS, Sealy TK, Khristova ML, et al. Newly discovered Ebolavirus associated with hemorrhagic fever outbreak in Uganda[J].PLoS Pathog, 2008, 4(11):e1000212.
[2] Listed N. Ebola haemorrhagic fever in Sudan, 1976 Report of aWHO/International Study Team[J]. Bull World Health Organ,1978, 56(2):247-270.
[3] Pourrut X, Kumulungui B, Wittmann T, et al. The natural historyof Ebola virus in Africa[J]. Microbes Infect, 2005, 7(7):1005-1014.
[4] Murray MJ. Ebola virus disease: a review of its past and presen[t J].Anesth Analg, 2015, 121(3):798-809.
[5] Gostin LO, Friedman EA. A retrospective and prospective analysisof the west African Ebola virus disease epidemic: robust nationalhealth systems at the foundation and an empowered WHO at theapex[J]. Lancet, 2015, 385(9980):1902-1909.
[6] Lupton HW, Lambert RD, Bumgardner DL, et al. Inactivatedvaccine for Ebola virus efficacious in guineapig model[J].Lancet, 1980, 316(8207):1294-1295.
[7] Dhama K, Karthik K, Khandia R, et al. Advances in designing anddeveloping vaccines, drugs, and therapies to counter Ebola viru[s J].Front Immunol, 2018, 9:1803.
[8] Wu XX, Yao HP, Wu NP, et al. Ebolavirus vaccines: progress inthe fight against Ebola virus disease[J]. Cell Physiol Biochem,2015, 37(5):1641-1658.
[9] 金宏丽,王化磊,郑学星,等. 埃博拉病毒病疫苗研究进展[J].传染病信息,2015, 28(2):70-74.
[10] 王雨潇,李靖欣,王杨,等. 埃博拉疫苗临床试验研究进展[J].传染病信息,2017,30(2):82-85.
[11] Martin JE, Sullivan NJ, Enama ME, et al. A DNA vaccine for Ebolavirus is safe and immunogenic in a phase I clinical trial[J]. ClinVaccine Immunol, 2006, 13(11):1267-1277.
[12] Sarwar UN, Costner P, Enama ME, et al. Safety and immunogenicityof DNA vaccines encoding Ebolavirus and Marburgvirus wild-typeglycoproteins in a phase I clinical trial[J]. J Infect Dis, 2015,211(4):549-557.
[13] Kibuuka H, Berkowitz NM, Millard M, et al. Safety andimmunogenicity of Ebola virus and Marburg virus glycoproteinDNA vaccines assessed separately and concomitantly in healthyUgandan adults: a phase 1b, randomised, double-blind, placebocontrolledclinical trial[J]. Lancet, 2015, 385(9977):1545-1554.
[14] Ebola GP vaccine[EB/OL]. [2018-09-16]. http://novavax.com/page/11/clinical-stage-pipeline.
[15] Milligan ID, Gibani MM, Sewell R, et al. Safety and immunogenicityof novel adenovirus type 26- and modified vaccinia Ankara-Vectored Ebola vaccines: a randomized clinical trial[J]. JAMA,2016, 315(15):1610-1623.
[16] Ledgerwood JE, Dezure AD, Stanley DA, et al. Chimpanzeeadenovirus vector Ebola vaccine[J]. N Engl J Med, 2015,373(8):928-938.
[17] De SO, Audran R, Pothin E, et al. Safety and immunogenicity of achimpanzee adenovirus-vectored Ebola vaccine in healthy adults:a randomised, double-blind, placebo-controlled, dose-finding,phase 1/2a study[J]. Lancet Infect Dis, 2016, 16(3):311-320.
[18] Tapia MD, Sow SO, Lyke KE, et al. Use of ChAd3-EBO-Z Ebola virus vaccine in Malian and US adults, and boosting of Malianadults with MVA-BN-Filo: a phase 1, single-blind, randomisedtrial, a phase 1b, open-label and double-blind, dose-escalationtrial, and a nested, randomised, double-blind, placebo-controlledtrial[J]. Lancet Infect Dis, 2016, 16(1):31-42.
[19] Ewer K, Rampling T, Venkatraman N, et al. A monovalentchimpanzee adenovirus Ebola vaccine boosted with MVA[J].New Engl J Med, 2016, 374(17):1635-1646.
[20] Kennedy SB, Bolay F, Kieh M, et al. Phase 2 placebo-controlledtrial of two vaccines to prevent Ebola in Liberia[J]. New Engl JMed, 2017, 377(15):1438-1447.
[21] Zhu FC, Hou LH, Li JX, et al. Safety and immunogenicity of anovel recombinant adenovirus type-5 vector-based Ebola vaccinein healthy adults in China: preliminary report of a randomised,double-blind, placebo-controlled, phase 1 trial[J]. Lancet,2015, 385(9984):2272-2279.
[22] Li JX, Hou LH, Meng FY, et al. Immunity duration of a recombinantadenovirus type-5 vector-based Ebola vaccine and a homologousprime-boost immunisation in healthy adults in China: final reportof a randomised, double-blind, placebo-controlled, phase 1 trial [J]. Lancet Glob Health, 2017, 5(3):e324-e334.
[23] Wu L, Zhang Z, Gao H, et al. Open-label phase I clinical trial ofAd5-EBOV in Africans in China[J]. Hum Vaccin Immunother,2017, 13(9):2078-2085.
[24] Zhu FC, Wurie AH, Hou LH, et al. Safety and immunogenicityof a recombinant adenovirus type-5 vector-based Ebola vaccinein healthy adults in Sierra Leone: a single-centre, randomised,double-blind, placebo-controlled, phase 2 trial[J]. Lancet,2016, 389(10069):621-628.
[25] Dolzhikova IV, Zubkova OV, Tukhvatulin AI, et al. Safety andimmunogenicity of GamEvac-Combi, a heterologous VSV- andAd5-vectored Ebola vaccine: an open phase I/II trial in healthyadults in Russia[J]. Human Vaccines, 2017, 13(3):613-620.
[26] Regules JA, Beigel JH, Paolino KM, et al. A recombinant vesicularstomatitis virus Ebola vaccine[J]. N Engl J Med, 2017, 376(4):330-341.
[27] Agnandji ST, Huttner A, Zinser ME, et al. Phase 1 trials of rVSVEbola vaccine in Africa and Europe[J]. N Engl J Med, 2016,374(17):1647-1660.
[28] Huttner A, Dayer JA, Yerly S, et al. The effect of dose on thesafety and immunogenicity of the VSV Ebola candidate vaccine: arandomised double-blind, placebo-controlled phase 1/2 trial[J].Lancet Infect Dis, 2015, 15(10):1156-1166.
[29] Agnandji ST, Fernandes JF, Bache EB, et al. Safety andimmunogenicity of rVSVΔG-ZEBOV-GP Ebola vaccine in adultsand children in Lambaréné, Gabon: a phase I randomised trial[J].PLoS Med, 2017, 14(10):e1002402.
[30] Heppner DG, Kemp TL, Martin BK, et al. Safety andimmunogenicity of the rVSV G-ZEBOV-GP Ebola virus vaccinecandidate in healthy adults: a phase 1b randomised, multicentre,double-blind, placebo-controlled, dose-response study[J].Lancet Infect Dis, 2017 17(8):854-866.
[31] Elsherif MS, Brown C, Mackinnoncameron D, et al. Assessing thesafety and immunogenicity of recombinant vesicular stomatitis virusEbola vaccine in healthy adults: a randomized clinical trial[J].CMAJ, 2017, 189(24):E819-E827.
[32] Huttner A, Agnandji ST, Combescure C, et al. Determinants ofantibody persistence across doses and continents after single-doserVSV-ZEBOV vaccination for Ebola virus disease: an observationalcohort study[J]. Lancet Infect Dis, 2018, 18(7):738-748.
[33] Widdowson MA, Schrag SJ, Carter RJ, et al. Implementing an Ebolavaccine study - Sierra Leone[J]. Mmwr Suppl, 2016, 65(3):98-106.
[34] Henao-Restrepo AM, Camacho A, Longini IM, et al. Efficacy andeffectiveness of an rVSV-vectored vaccine in preventing Ebolavirus disease: final results from the Guinea ring vaccination, openlabel,cluster-randomised trial (Ebola ?a Suffit!) [J]. Lancet,2017, 389(10068):505-518.
[35] Halperin SA, Arribas JR, Rupp R, et al. Six-month safety data ofrecombinant vesicular stomatitis virus-Zaire Ebola virus envelopeglycoprotein vaccine in a phase 3 double-blind, placebo-controlledrandomized study in healthy adults[J]. J Infect Dis, 2017,215(12):1789-1798.
[36] Medaglini D, Harandi AM, Ottenhoff TH, et al. Ebola vaccine R&D: filling the knowledge gaps[J]. Sci Transl Med, 2015,7(317):317ps24.
[37] Farooq F, Beck K, Paolino KM, et al. Circulating follicular T helpercells and cytokine profile in humans following vaccination with therVSV-ZEBOV Ebola vaccine[J]. Sci Rep, 2016, 6:27944.
[38] Dahlke C, Kasonta R, Lunemann S, et al. Dose-dependentT-cell dynamics and cytokine cascade following rVSV-ZEBOVimmunization[J]. EBioMedicine, 2017, 19:107-118.
[39] Rechtien A, Richert L, Lorenzo H, et al. Systems vaccinologyidentifies an early innate immune signature as a correlate ofantibody responses to the Ebola vaccine rVSV-ZEBOV[J]. CellRep, 2017, 20(9):2251-2261.
[40] Huttner A, Combescure C, Grillet S, et al. A dose-dependentplasma signature of the safety and immunogenicity of the rVSVEbolavaccine in Europe and Africa[J]. Sci Transl Med, 2017,9(385)pii:eaaj1701.


[ 基金项目] 重大新药创制专项(2016ZX09106003-001)
[ 作者单位] 100071 北京,军事科学院军事医学研究院生物 工程研究所(张哲、侯利华)
[ 通信作者] 侯利华,E-mail: houlihua@sina.com
更新日期/Last Update: 2018-10-30