Phase 1 Trials of rVSV Ebola Vaccine in Africa and Europe.
Phase 1 Trials of rVSV Ebola Vaccine in Africa and Europe.
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DOI：
10.1056/nejmoa1502924
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发表时间：
2016-04-28
期刊：
影响因子：
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通讯作者：
Siegrist CA
中科院分区：
文献类型：
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作者：
Agnandji ST;Huttner A;Zinser ME;Njuguna P;Dahlke C;Fernandes JF;Yerly S;Dayer JA;Kraehling V;Kasonta R;Adegnika AA;Altfeld M;Auderset F;Bache EB;Biedenkopf N;Borregaard S;Brosnahan JS;Burrow R;Combescure C;Desmeules J;Eickmann M;Fehling SK;Finckh A;Goncalves AR;Grobusch MP;Hooper J;Jambrecina A;Kabwende AL;Kaya G;Kimani D;Lell B;Lemaître B;Lohse AW;Massinga-Loembe M;Matthey A;Mordmüller B;Nolting A;Ogwang C;Ramharter M;Schmidt-Chanasit J;Schmiedel S;Silvera P;Stahl FR;Staines HM;Strecker T;Stubbe HC;Tsofa B;Zaki S;Fast P;Moorthy V;Kaiser L;Krishna S;Becker S;Kieny MP;Bejon P;Kremsner PG;Addo MM;Siegrist CA
在西非使用前，选择表达扎伊尔埃博拉病毒（ZEBOV）糖蛋白的可复制重组水疱性口炎病毒（rVSV）疫苗进行快速安全性和免疫原性测试。我们进行了三项开放标签、剂量递增的1期试验和一项随机、双盲、对照的1期试验，以评估欧洲和非洲158名健康成人中不同剂量的rVSV-ZEBOV的安全性、副作用特征和免疫原性。所有参与者都注射了30万至5000万个噬斑形成单位（PFU）的疫苗或安慰剂。未报告严重疫苗相关不良事件。轻度至中度早发性反应原性常见但短暂（中位数，1天）。在高达30%的接种者中观察到发烧。在接受300万PFU或更多的130名参与者中，123名（95%）在3天内检测到疫苗病毒血症;唾液或尿液中未检测到rVSV。在注射后第二周，日内瓦的51名参与者中有11名（22%）发生了影响1 - 4个关节的关节炎，疼痛持续时间中位数为8天（四分位数范围，4 - 87）;德国汉堡和肯尼亚基利菲的60名参与者（3%）发生了2例自限性病例。在另外2名疫苗接种者的一份滑液抽吸物和皮肤囊泡中鉴定出病毒，表明在免疫后第二周有外周病毒复制。在所有参与者中检测到ZEBOV-糖蛋白特异性抗体应答，具有相似的糖蛋白结合抗体滴度，但在较高剂量下具有显著较高的中和抗体滴度。所有参与者的糖蛋白结合抗体滴度持续180天。在这些研究中，rVSV-ZEBOV是反应原性的，但在单次给药后具有免疫原性，需要进一步评估安全性和有效性。（由Wellcome Trust和其他人资助; ClinicalTrials.gov编号，NCT 02283099，NCT 02287480和NCT 02296983;泛非临床试验注册编号，PACTR 201411000919191。
The replication-competent recombinant vesicular stomatitis virus (rVSV)–based vaccine expressing a Zaire ebolavirus (ZEBOV) glycoprotein was selected for rapid safety and immunogenicity testing before its use in West Africa. We performed three open-label, dose-escalation phase 1 trials and one randomized, double-blind, controlled phase 1 trial to assess the safety, side-effect profile, and immunogenicity of rVSV-ZEBOV at various doses in 158 healthy adults in Europe and Africa. All participants were injected with doses of vaccine ranging from 300,000 to 50 million plaque-forming units (PFU) or placebo. No serious vaccine-related adverse events were reported. Mild-to-moderate early-onset reactogenicity was frequent but transient (median, 1 day). Fever was observed in up to 30% of vaccinees. Vaccine viremia was detected within 3 days in 123 of the 130 participants (95%) receiving 3 million PFU or more; rVSV was not detected in saliva or urine. In the second week after injection, arthritis affecting one to four joints developed in 11 of 51 participants (22%) in Geneva, with pain lasting a median of 8 days (interquartile range, 4 to 87); 2 self-limited cases occurred in 60 participants (3%) in Hamburg, Germany, and Kilifi, Kenya. The virus was identified in one synovial-fluid aspirate and in skin vesicles of 2 other vaccinees, showing peripheral viral replication in the second week after immunization. ZEBOV-glycoprotein–specific antibody responses were detected in all the participants, with similar glycoprotein-binding antibody titers but significantly higher neutralizing antibody titers at higher doses. Glycoprotein-binding antibody titers were sustained through 180 days in all participants. In these studies, rVSV-ZEBOV was reactogenic but immunogenic after a single dose and warrants further evaluation for safety and efficacy. (Funded by the Wellcome Trust and others; ClinicalTrials.gov numbers, NCT02283099, NCT02287480, and NCT02296983; Pan African Clinical Trials Registry number, PACTR201411000919191.)