Single Immunization With a Monovalent Vesicular Stomatitis Virus-Based Vaccine Protects Nonhuman Primates Against Heterologous Challenge With Bundibugyo ebolavirus

Single Immunization With a Monovalent Vesicular Stomatitis Virus-Based Vaccine Protects Nonhuman Primates Against Heterologous Challenge With Bundibugyo ebolavirus
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DOI:
10.1093/infdis/jir350
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发表时间:
2011-11-01
影响因子:
6.4
通讯作者:
Feldmann, Heinz
Feldmann, Heinz
中科院分区:
医学2区
文献类型:
--
作者:
Falzarano, Darryl;Feldmann, Friederike;Feldmann, Heinz

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表达丝状病毒糖蛋白的基于重组水泡性口炎病毒 (rVSV) 载体的单价疫苗平台已被证明可以在预防性和暴露后提供针对埃博拉 (EBOV) 和马尔堡 (MARV) 病毒致命攻击的保护。该平台提供物种内异源菌株之间的保护;然而,针对物种间致命挑战的保护基本上不成功。为了确定 rVSV-EBOV 疫苗是否具有针对新出现的系统发育相关物种提供保护的潜力,食蟹猴接种了表达扎伊尔埃博拉病毒 (ZEBOV) 或科特迪瓦埃博拉病毒 (CIEBOV) 糖蛋白的 rVSV 疫苗,然后用最近被提议作为新埃博拉病毒物种的本迪布焦埃博拉病毒 (BEBOV) 进行攻击2007 年乌干达爆发疫情后。单次接种 ZEBOV 特异性疫苗可针对随后的 BEBOV 攻击提供交叉保护(75% 存活率),而接种 CIEBOV 特异性疫苗则产生与模拟免疫动物相似的结果(分别为 33% 和 25% 存活率)。这表明基于 rVSV 的单价疫苗可能对新出现的物种有用;然而,跨物种的异源保护仍然具有挑战性,可能取决于通过加强免疫或通过包含多种免疫原来增强免疫反应。
The recombinant vesicular stomatitis virus (rVSV) vector-based monovalent vaccine platform expressing a filovirus glycoprotein has been demonstrated to provide protection from lethal challenge with Ebola (EBOV) and Marburg (MARV) viruses both prophylactically and after exposure. This platform provides protection between heterologous strains within a species; however, protection from lethal challenge between species has been largely unsuccessful. To determine whether the rVSV-EBOV vaccines have the potential to provide protection against a newly emerging, phylogenetically related species, cynomolgus macaques were vaccinated with an rVSV vaccine expressing either the glycoprotein of Zaire ebolavirus (ZEBOV) or Cote d'Ivoire ebolavirus (CIEBOV) and then challenged with Bundibugyo ebolavirus (BEBOV), which was recently proposed as a new EBOV species following an outbreak in Uganda in 2007. A single vaccination with the ZEBOV-specific vaccine provided cross-protection (75% survival) against subsequent BEBOV challenge, whereas vaccination with the CIEBOV-specific vaccine resulted in an outcome similar to mock-immunized animals (33% and 25% survival, respectively). This demonstrates that monovalent rVSV-based vaccines may be useful against a newly emerging species; however, heterologous protection across species remains challenging and may depend on enhancing the immune responses either through booster immunizations or through the inclusion of multiple immunogens.