Canadian Center for Vaccinology (ElSherif, Brown, MacKinnon-Cameron, Li, McNeil, Langley, Halperin), IWK Health Centre and Nova Scotia Health Authority, Dalhousie University, Halifax, NS; National Microbiology Laboratory (Racine, Alimonti), Winnipeg, Man.; Battelle Biomedical Research Center (Rudge, Sabourin), Columbus, Ohio; United States Army Medical Research Institute of Infectious Disease (Silvera, Hooper, Kwilas), Fort Detrick, Md.; Joint Program Executive Office for Chemical and Biological Defense Medical Countermeasure Systems' Joint Vaccine Acquisition Program (Kilgore, Badorrek), Fort Detrick, Md.; BioProtection Systems/NewLink Genetics Corporation (Ramsey, Heppner, Kemp, Monath), Ames, Iowa; Veristat LLC (Nowak), Southborough, Mass.
CMAJ. 2017 Jun 19;189(24):E819-E827. doi: 10.1503/cmaj.170074.
The 2013-2016 Ebola virus outbreak in West Africa was the most widespread in history. In response, alive attenuated recombinant vesicular stomatitis virus (rVSV) vaccine expressing glycoprotein (rVSVΔG-ZEBOV-GP) was evaluated in humans.
In a phase 1, randomized, dose-ranging, observer-blind, placebo-controlled trial, healthy adults aged 18-65 years were randomized into 4 groups of 10 to receive one of 3 vaccine doses or placebo. Follow-up visits spanned 180 days postvaccination for safety monitoring, immunogenicity testing and any rVSV virus shedding.
Forty participants were injected with rVSVΔG-ZEBOV-GP vaccine ( = 30) or saline placebo ( = 10). No serious adverse events related to the vaccine or participant withdrawals were reported. Solicited adverse events during the 14-day follow-up period were mild to moderate and self-limited, with the exception of injection-site pain and headache. Viremia following vaccination was transient and no longer detectable after study day 3, with no virus shedding in saliva or urine. All vaccinated participants developed serum immunoglobulin G (IgG), as measured by Ebola virus envelope glycoprotein-based enzyme-linked immunosorbent assay (ELISA). Immunogenicity was comparable across all dose groups, and sustained IgG titers were detectable through to the last visit, at study day 180.
In this phase 1 study, there were no safety concerns after a single dose of rVSVΔG-ZEBOV-GP vaccine. IgG ELISA showed persistent high titers at 180 days postimmunization. There was a period of reactogenicity, but in general, the vaccine was well tolerated. This study provides evidence of the safety and immunogenicity of rVSVΔG-ZEBOV-GP vaccine and importance of its further investigation. Clinical-Trials.gov no., NCT02374385.
2013 年至 2016 年期间在西非爆发的埃博拉疫情是历史上传播范围最广的一次。为应对疫情，一种表达糖蛋白的活减毒重组水疱性口炎病毒（rVSVΔG-ZEBOV-GP）疫苗被用于人体试验。
在一项 1 期、随机、剂量范围、观察者盲法、安慰剂对照临床试验中，18-65 岁的健康成年人被随机分为 4 组，每组 10 人，分别接种 3 种剂量的疫苗或安慰剂。接种后随访 180 天，监测安全性、免疫原性和任何 rVSV 病毒脱落情况。
40 名参与者接受了 rVSVΔG-ZEBOV-GP 疫苗（n = 30）或生理盐水安慰剂（n = 10）注射。未报告与疫苗相关的严重不良事件或参与者退出。接种后 14 天的不良事件为轻度至中度，且为自限性，除注射部位疼痛和头痛外。接种后一过性病毒血症，研究第 3 天起不再检测到病毒，唾液或尿液中也未检测到病毒脱落。所有接种疫苗的参与者均产生了埃博拉病毒包膜糖蛋白酶联免疫吸附试验（ELISA）检测的血清免疫球蛋白 G（IgG）。各剂量组的免疫原性相当，接种后第 180 天的最后一次随访时仍可检测到持续高滴度的 IgG。
在这项 1 期研究中，单次接种 rVSVΔG-ZEBOV-GP 疫苗后未出现安全性问题。IgG ELISA 显示，接种后 180 天仍保持高滴度。存在一段时间的反应原性，但总体而言，疫苗具有良好的耐受性。这项研究为 rVSVΔG-ZEBOV-GP 疫苗的安全性和免疫原性提供了证据，并强调了其进一步研究的重要性。临床试验.gov 注册号：NCT02374385。
