Stat1-Deficient Mice Are Not an Appropriate Model for Efficacy Testing of Recombinant Vesicular Stomatitis Virus-Based Filovirus Vaccines
Stat1-Deficient Mice Are Not an Appropriate Model for Efficacy Testing of Recombinant Vesicular Stomatitis Virus-Based Filovirus Vaccines
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DOI：
10.1093/infdis/jiv188
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发表时间：
2015-10-01
影响因子：
6.4
通讯作者：
Feldmann, Heinz
中科院分区：
文献类型：
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作者：
Marzi, Andrea;Kercher, Lisa;Feldmann, Heinz
Stat1(-/-) 小鼠缺乏对干扰素 α、β 和 γ 的反应，从而允许复制未适应的野生型 (wt) 埃博拉病毒和马尔堡病毒。我们试图建立一种小鼠模型，用于使用野生型埃博拉病毒和马尔堡病毒攻击株对基于活减毒重组水泡性口炎病毒（rVSV）的丝状病毒疫苗载体进行功效测试。虽然用不同的基于 rVSV 的丝状病毒载体感染具有免疫活性的小鼠不会引起疾病，但用相同的载体感染 Stat1(-/-) 小鼠会导致大多数测试的 rVSV 的全身感染和致死结果。尽管病毒载量存在差异，但 rVSV 丝状病毒疫苗载体和 rVSVwt 之间的器官趋向性非常相似，但大脑除外。总之，Stat1(-/-) 小鼠不是适合用于减毒、具有复制能力的 rVSV 疫苗载体功效测试的免疫受损小鼠模型。
Stat1(-/-) mice lack a response to interferon alpha, beta, and gamma, allowing for replication of nonadapted wild-type (wt) Ebolavirus and Marburgvirus. We sought to establish a mouse model for efficacy testing of live attenuated recombinant vesicular stomatitis virus (rVSV)-based filovirus vaccine vectors using wt Ebolavirus and Marburgvirus challenge strains. While infection of immunocompetent mice with different rVSV-based filovirus vectors did not cause disease, infection of Stat1(-/-) mice with the same vectors resulted in systemic infection and lethal outcome for the majority of tested rVSVs. Despite differences in viral loads, organ tropism was remarkably similar between rVSV filovirus vaccine vectors and rVSVwt, with the exception of the brain. In conclusion, Stat1(-/-) mice are not an appropriate immunocompromised mouse model for efficacy testing of live attenuated, replication-competent rVSV vaccine vectors.