A Recombinant Vesicular Stomatitis Virus-Based Vaccine Provides Postexposure Protection Against Bundibugyo Ebolavirus Infection.
A Recombinant Vesicular Stomatitis Virus-Based Vaccine Provides Postexposure Protection Against Bundibugyo Ebolavirus Infection.
复制标题
重组水泡性口炎病毒疫苗可提供针对本迪布焦埃博拉病毒感染的暴露后保护。
DOI：
10.1093/infdis/jiad207
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Geisbert,ThomasW
中科院分区：
文献类型：
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作者：
Woolsey,Courtney;Strampe,Jamie;Fenton,KarlaA;Agans,KrystleN;Martinez,Jasmine;Borisevich,Viktoriya;Dobias,NatalieS;Deer,DanielJ;Geisbert,JoanB;Cross,RobertW;Connor,JohnH;Geisbert,ThomasW
背景本迪布焦病毒（BDBV）是一种严重的病毒性疾病，其致死率约为20%-51%。在美国，Ervebo是唯一获得许可的丝状病毒疫苗，由表达埃博拉病毒（EBOV）糖蛋白（GP）的重组水泡性口炎病毒（rVSV）载体组成。Ervebo在临床试验中被证明可以快速预防致命的埃博拉病毒;然而，该疫苗仅适用于EBOV。方法为了检验rVSV疫苗候选物rVSVΔG/BDBV-GP是否可以提供针对BDBV的治疗保护，我们用1000噬斑形成单位的BDBV接种七只食蟹猴，其中6只在感染后20-23分钟注射rVSVΔG/BDBV-GP疫苗，结果5只动物感染后存活（83%）。相比之下，在这个猕猴模型中，预期的自然存活率为21%。所有治疗动物均显示出早期循环免疫应答，而未治疗动物则没有。存活的动物显示出GP特异性IgM和IgG产生的证据，而死亡的动物没有产生显着的IgG.ConclusionsThis小，概念验证研究表明，早期治疗rVSVΔG/BDBV-GP提供了一个生存的好处，在这个非人灵长类动物模型的BDBV感染，可能通过早期启动适应性免疫。
BackgroundThe filovirus Bundibugyo virus (BDBV) causes severe disease with a mortality rate of approximately 20%–51%. The only licensed filovirus vaccine in the United States, Ervebo, consists of a recombinant vesicular stomatitis virus (rVSV) vector that expresses Ebola virus (EBOV) glycoprotein (GP). Ervebo was shown to rapidly protect against fatal Ebola disease in clinical trials; however, the vaccine is only indicated against EBOV. Recent outbreaks of other filoviruses underscore the need for additional vaccine candidates, particularly for BDBV infections.MethodsTo examine whether the rVSV vaccine candidate rVSVΔG/BDBV-GP could provide therapeutic protection against BDBV, we inoculated seven cynomolgus macaques with 1000 plaque-forming units of BDBV, administering rVSVΔG/BDBV-GP vaccine to 6 of them 20–23 minutes after infection.ResultsFive of the treated animals survived infection (83%) compared to an expected natural survival rate of 21% in this macaque model. All treated animals showed an early circulating immune response, while the untreated animal did not. Surviving animals showed evidence of both GP-specific IgM and IgG production, while animals that succumbed did not produce significant IgG.ConclusionsThis small, proof-of-concept study demonstrated early treatment with rVSVΔG/BDBV-GP provides a survival benefit in this nonhuman primate model of BDBV infection, perhaps through earlier initiation of adaptive immunity.