A Recombinant Vesicular Stomatitis Virus Ebola Vaccine.
A Recombinant Vesicular Stomatitis Virus Ebola Vaccine.
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DOI：
10.1056/nejmoa1414216
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发表时间：
2017-01-26
期刊：
影响因子：
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通讯作者：
rVSVΔG-ZEBOV-GP Study Group
中科院分区：
文献类型：
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作者：
Regules JA;Beigel JH;Paolino KM;Voell J;Castellano AR;Hu Z;Muñoz P;Moon JE;Ruck RC;Bennett JW;Twomey PS;Gutiérrez RL;Remich SA;Hack HR;Wisniewski ML;Josleyn MD;Kwilas SA;Van Deusen N;Mbaya OT;Zhou Y;Stanley DA;Jing W;Smith KS;Shi M;Ledgerwood JE;Graham BS;Sullivan NJ;Jagodzinski LL;Peel SA;Alimonti JB;Hooper JW;Silvera PM;Martin BK;Monath TP;Ramsey WJ;Link CJ;Lane HC;Michael NL;Davey RT Jr;Thomas SJ;rVSVΔG-ZEBOV-GP Study Group
历史上最严重的埃博拉病毒病（EVD）爆发已导致28，000多例病例和11，000人死亡。我们提出了两个减毒，复制能力，重组水泡性口炎病毒（rVSV）为基础的候选疫苗，旨在预防EVD的1期试验的最终结果。我们对表达埃博拉病毒扎伊尔株（ZEBOV）糖蛋白的rVSV候选疫苗进行了两项1期、安慰剂对照、双盲、剂量递增试验。每个研究中心共有39名成人（共78名参与者）连续入组，每组13人。在每个研究中心，志愿者接受三种剂量的rVSV-ZEBOV疫苗（300万个噬斑形成单位[PFU]，2000万个PFU或1亿个PFU）或安慰剂。其中一个研究中心的志愿者在第28天接受第二次给药。评估了安全性和免疫原性。最常见的不良反应是注射部位疼痛、疲劳、肌痛和头痛。在第1次接种后，在所有疫苗接种者中均观察到一过性rVSV病毒血症。第二次给药后不良事件和病毒血症的发生率低于第一次给药后。到第28天，通过针对ZEBOV-Kikwit毒株的糖蛋白的酶联免疫吸附测定（ELISA）评估，所有疫苗接受者都具有血清转化。在第28天，如通过ELISA和通过假病毒体中和测定所评估的，在接受2000万PFU或1亿PFU的组中针对ZEBOV糖蛋白的抗体的几何平均滴度高于接受300万PFU的组。第1次给药后28天的第二次给药在第56天显著增加了抗体滴度，但在6个月时效果减弱。这种埃博拉候选疫苗引发了抗埃博拉抗体反应。疫苗接种后，rVSV病毒血症频繁发生，但为一过性。这些结果支持进一步评价用于暴露前预防的2000万PFU疫苗剂量，并表明第二剂疫苗可增强抗体应答。（由美国国立卫生研究院和其他机构资助; rVSVΔG-ZEBOV-GP ClinicalTrials.gov编号，NCT 02269423和NCT 02280408。
The worst Ebola virus disease (EVD) outbreak in history has resulted in more than 28,000 cases and 11,000 deaths. We present the final results of two phase 1 trials of an attenuated, replication-competent, recombinant vesicular stomatitis virus (rVSV)–based vaccine candidate designed to prevent EVD. We conducted two phase 1, placebo-controlled, double-blind, dose-escalation trials of an rVSV-based vaccine candidate expressing the glycoprotein of a Zaire strain of Ebola virus (ZEBOV). A total of 39 adults at each site (78 participants in all) were consecutively enrolled into groups of 13. At each site, volunteers received one of three doses of the rVSV-ZEBOV vaccine (3 million plaque-forming units [PFU], 20 million PFU, or 100 million PFU) or placebo. Volunteers at one of the sites received a second dose at day 28. Safety and immunogenicity were assessed. The most common adverse events were injection-site pain, fatigue, myalgia, and headache. Transient rVSV viremia was noted in all the vaccine recipients after dose 1. The rates of adverse events and viremia were lower after the second dose than after the first dose. By day 28, all the vaccine recipients had seroconversion as assessed by an enzyme-linked immunosorbent assay (ELISA) against the glycoprotein of the ZEBOV-Kikwit strain. At day 28, geometric mean titers of antibodies against ZEBOV glycoprotein were higher in the groups that received 20 million PFU or 100 million PFU than in the group that received 3 million PFU, as assessed by ELISA and by pseudovirion neutralization assay. A second dose at 28 days after dose 1 significantly increased antibody titers at day 56, but the effect was diminished at 6 months. This Ebola vaccine candidate elicited anti-Ebola antibody responses. After vaccination, rVSV viremia occurred frequently but was transient. These results support further evaluation of the vaccine dose of 20 million PFU for preexposure prophylaxis and suggest that a second dose may boost antibody responses. (Funded by the National Institutes of Health and others; rVSVΔG-ZEBOV-GP ClinicalTrials.gov numbers, NCT02269423 and NCT02280408.)