埃博拉糖蛋白特异性马多克隆抗体产品对 Guinea Pigs 致死性埃博拉病毒感染的疗效。
Efficacy of Ebola Glycoprotein-Specific Equine Polyclonal Antibody Product Against Lethal Ebola Virus Infection in Guinea Pigs.
机构信息
Special Pathogens, Public Health Agency of Canada, Winnipeg, Manitoba.
Department of Medical Microbiology, University of Manitoba, Winnipeg, Canada.
出版信息
J Infect Dis. 2018 Nov 22;218(suppl_5):S603-S611. doi: 10.1093/infdis/jiy329.
BACKGROUND
Filoviruses including Ebola, Sudan, and other species are emerging zoonotic pathogens representing a significant public health concern with high outbreak potential, and they remain a potential bioterrorism-related threat. We have developed a despeciated equine Ebola polyclonal antibody (E-EIG) postexposure treatment against Ebola virus (EBOV) and evaluated its efficacy in the guinea pig model of EBOV infection.
METHODS
Guinea pigs were infected with guinea pig-adapted EBOV (Mayinga strain) and treated with various dose levels of E-EIG (20-100 mg/kg) twice daily for 6 days starting at 24 h postinfection. The E-EIG was also assessed for neutralization activity against related filoviruses including EBOV strains Mayinga, Kikwit, and Makona and the Bundibugyo and Taï Forest ebolavirus species.
RESULTS
Treatment with E-EIG conferred 83% to 100% protection in guinea pigs. The results demonstrated a comparable neutralization activity (range, 1:512-1:896) of E-EIG against all tested strains, suggesting the potential for cross-protection with the polyclonal antibody therapeutic.
CONCLUSIONS
This study showed that equine-derived polyclonal antibodies are efficacious against lethal EBOV disease in a relevant animal model. Furthermore, the studies support the utility of the equine antibody platform for the rapid production of a therapeutic product in the event of an outbreak by a filovirus or other zoonotic pathogen.
背景
埃博拉、苏丹等丝状病毒是新兴的人畜共患病原体，具有很高的暴发潜力，对公共卫生构成重大威胁，仍然是潜在的与生物恐怖主义相关的威胁。我们已经开发出一种脱毒马埃博拉多克隆抗体（E-EIG），用于埃博拉病毒（EBOV）的暴露后治疗，并在埃博拉病毒感染的豚鼠模型中评估了其疗效。
方法
豚鼠感染豚鼠适应的埃博拉病毒（Mayinga 株），并在感染后 24 小时开始每天两次接受不同剂量水平的 E-EIG（20-100mg/kg）治疗 6 天。还评估了 E-EIG 对相关丝状病毒（包括 EBOV 株 Mayinga、Kikwit 和 Makona 以及 Bundibugyo 和 Taï Forest 埃博拉病毒种）的中和活性。
结果
用 E-EIG 治疗可使豚鼠获得 83%至 100%的保护率。结果表明，E-EIG 对所有测试株的中和活性相当（范围为 1:512-1:896），表明多克隆抗体治疗具有交叉保护的潜力。
结论
本研究表明，马源多克隆抗体在相关动物模型中对致命性 EBOV 疾病有效。此外，这些研究支持了马抗体平台在丝状病毒或其他人畜共患病原体暴发时快速生产治疗产品的实用性。
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