Vesicular stomatitis virus-based vaccines protect nonhuman primates against Bundibugyo ebolavirus.
Vesicular stomatitis virus-based vaccines protect nonhuman primates against Bundibugyo ebolavirus.
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DOI：
10.1371/journal.pntd.0002600
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发表时间：
2013
影响因子：
3.8
通讯作者：
Geisbert TW
中科院分区：
文献类型：
--
作者：
Mire CE;Geisbert JB;Marzi A;Agans KN;Feldmann H;Geisbert TW
埃博拉病毒（EBOV）在人类和非人类灵长类动物（NHPs）中引起严重且往往致命的出血热。目前，没有许可的疫苗或治疗方法供人类使用。基于重组水疱性口炎病毒（rVSV）的疫苗载体编码了一种EBOV糖蛋白来代替VSV糖蛋白，在国家卫生保健计划中显示出对同源苏丹埃博拉病毒（SEBOV）或扎伊尔埃博拉病毒（ZEBOV）攻击的100%有效性。此外，单次注射三种rVSV载体的混合物完全保护NHPs免受SEBOV、ZEBOV、前Côte科特迪瓦埃博拉病毒和马尔堡病毒的攻击。然而，最近的研究表明，使用几种不同的异源丝状病毒疫苗来完全预防新发现的本迪布焦埃博拉病毒（BEBOV）更为困难，并提出了新的挑战。由于BEBOV在最近的一次疫情中造成近50%的死亡率，任何先进的用于人类的丝状病毒疫苗都必须能够抵御这种新物种。在这里，我们评估了几种使用基于rvsv的疫苗对抗BEBOV的不同策略。对食蟹猕猴进行单次注射同源BEBOV疫苗、单次注射混合异源疫苗（SEBOV/ZEBOV）或使用异源SEBOV和ZEBOV载体的初强化疫苗接种。动物在初次接种后29-36天感染BEBOV病毒。接种了同源BEBOV疫苗或初级强化疫苗的猕猴没有明显的疾病迹象，并在挑战中存活下来。相比之下，接种异种混合疫苗的动物和未接种疫苗的对照动物出现与BEBOV感染相符的严重临床症状，每组3只动物中有2只死亡。这些数据表明，对BEBOV的完全保护可能需要在疫苗中加入BEBOV糖蛋白或采用初始强化方案。幸运的是，我们的研究结果表明，在启动-增强方法中采用的基于rvsv的异源丝状病毒疫苗载体可以使用简化方案提供对BEBOV的保护，这可能在爆发环境中具有实用价值。埃博拉病毒（EBOV）共有5个物种，由于其高死亡率和用作生物恐怖主义制剂的潜力，被几个美国政府机构归类为A类优先病原体和一级选择制剂。目前，还没有批准用于人类的疫苗或治疗方法。表达丝状病毒糖蛋白（GP）的具有复制能力的重组水疱性口炎病毒（rVSV）载体在丝状病毒感染的致死性非人灵长类动物（NHP）模型中显示出作为单次注射预防性疫苗和暴露后治疗的前景。最近爆发的第五种已知埃博拉病毒——本迪布焦埃博拉病毒（BEBOV），表明需要能够迅速部署的疫苗，以对抗一种新的线状病毒物种的爆发。迄今为止，基于rvsv -丝状病毒gp的疫苗仅能够抵御EBOV同源物种的攻击。在这里，我们证明了在最初BEBOV爆发时可用的两种基于rvsv的异源丝状病毒疫苗可以通过短时间的预加强疫苗接种策略保护NHPs免受BEBOV的攻击。虽然初级-加强战略取得了成功，但单一注射混合疫苗接种战略与相同的疫苗载体未能提供保护。这些数据表明，缩短的36天初始强化方案可能有助于快速应对埃博拉病毒新物种引起的疫情。
Ebola virus (EBOV) causes severe and often fatal hemorrhagic fever in humans and nonhuman primates (NHPs). Currently, there are no licensed vaccines or therapeutics for human use. Recombinant vesicular stomatitis virus (rVSV)-based vaccine vectors, which encode an EBOV glycoprotein in place of the VSV glycoprotein, have shown 100% efficacy against homologous Sudan ebolavirus (SEBOV) or Zaire ebolavirus (ZEBOV) challenge in NHPs. In addition, a single injection of a blend of three rVSV vectors completely protected NHPs against challenge with SEBOV, ZEBOV, the former Côte d'Ivoire ebolavirus, and Marburg virus. However, recent studies suggest that complete protection against the newly discovered Bundibugyo ebolavirus (BEBOV) using several different heterologous filovirus vaccines is more difficult and presents a new challenge. As BEBOV caused nearly 50% mortality in a recent outbreak any filovirus vaccine advanced for human use must be able to protect against this new species. Here, we evaluated several different strategies against BEBOV using rVSV-based vaccines. Groups of cynomolgus macaques were vaccinated with a single injection of a homologous BEBOV vaccine, a single injection of a blended heterologous vaccine (SEBOV/ZEBOV), or a prime-boost using heterologous SEBOV and ZEBOV vectors. Animals were challenged with BEBOV 29–36 days after initial vaccination. Macaques vaccinated with the homologous BEBOV vaccine or the prime-boost showed no overt signs of illness and survived challenge. In contrast, animals vaccinated with the heterologous blended vaccine and unvaccinated control animals developed severe clinical symptoms consistent with BEBOV infection with 2 of 3 animals in each group succumbing. These data show that complete protection against BEBOV will likely require incorporation of BEBOV glycoprotein into the vaccine or employment of a prime-boost regimen. Fortunately, our results demonstrate that heterologous rVSV-based filovirus vaccine vectors employed in the prime-boost approach can provide protection against BEBOV using an abbreviated regimen, which may have utility in outbreak settings. Ebola viruses (EBOV), of which there are five species, are categorized as Category A Priority Pathogens and Tier 1 Select Agents by several US Government agencies as a result of their high mortality rates and potential for use as agents of bioterrorism. Currently, there are no vaccines or therapeutics approved for human use. Replication-competent, recombinant vesicular stomatitis virus (rVSV) vectors expressing filovirus glycoproteins (GP), in place of the VSV glycoprotein have shown promise in lethal nonhuman primate (NHP) models of filovirus infection as both single injection preventive vaccines and as post-exposure treatments. The recent outbreak of the fifth recognized EBOV species, Bundibugyo ebolavirus (BEBOV), demonstrates the need for vaccines that can be rapidly deployed to combat an outbreak of a new filovirus species. To date, rVSV-filovirus GP-based vaccines have only been able to protect against challenge with a homologous species of EBOV. Here, we show that the two heterologous rVSV-based filovirus vaccines available at the time of the original BEBOV outbreak can protect NHPs against BEBOV challenge using a short prime-boost vaccination strategy. While the prime-boost strategy was successful, a single injection blended vaccination strategy with the same vaccine vectors failed to provide protection. These data suggest that an abbreviated prime-boost regimen of 36 days may have utility for quickly responding to outbreaks caused by new species of EBOV.
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DOI：
10.1073/pnas.92.10.4477
发表时间：
1995-05-09
影响因子：
11.1
作者：
LAWSON, ND;STILLMAN, EA;ROSE, JK
通讯作者：
ROSE, JK
影响因子：
6.4
作者：
Kobinger, Gary P.;Leung, Anders;Weingartl, Hana M.
通讯作者：
Weingartl, Hana M.
影响因子：
5.4
作者：
Bukreyev, Alexander;Rollin, Pierre E.;Sanchez, Anthony
通讯作者：
Sanchez, Anthony
影响因子：
6.4
作者：
Falzarano, Darryl;Feldmann, Friederike;Feldmann, Heinz
通讯作者：
Feldmann, Heinz
DOI：
10.1084/jem.20011500
发表时间：
2002-03-04
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Bavari S;Bosio CM;Wiegand E;Ruthel G;Will AB;Geisbert TW;Hevey M;Schmaljohn C;Schmaljohn A;Aman MJ
通讯作者：
Aman MJ