Pre- and post-exposure safety and e

Pre- and post-exposure safety and efficacy of attenuated rabies virus vaccines are enhanced by their expression of IFNγ.
Barkhouse DA , Faber M , Hooper DC .
Abstract
Consistent with evidence of a strong correlation between interferon gamma (IFNγ) production and rabies virus (RABV) clearance from the CNS, we recently demonstrated that engineering a pathogenic RABV to express IFNγ highly attenuates the virus. Reasoning that IFNγ expression by RABV vaccines would enhance their safety and efficacy, we reverse-engineered two proven vaccine vectors, GAS and GASGAS, to express murine IFNγ. Mortality and morbidity were monitored during suckling mice infection, immunize/challenge experiments and mixed intracranial infections. We demonstrate that GASγ and GASγGAS are significantly attenuated in suckling mice compared to the GASGAS vaccine. GASγ better protects mice from lethal DRV4 RABV infection in both pre- and post-exposure experiments compared to GASGAS. Finally, GASγGAS reduces post-infection neurological sequelae, compared to control, during mixed intracranial infection with DRV4. These data show IFNγ expression by a vaccine vector can enhance its safety while increasing its efficacy as pre- and post-exposure treatment.

結果 (中文) 1:

提高了他们的 IFNγ 表达前和暴露后的安全和狂犬病减毒的病毒疫苗免疫效果。Barkhouse 大，费伯 M，Hooper 直流。摘要符合的干扰素 γ (IFNγ) 生产与狂犬病病毒 （株） 间隙从中枢神经系统的强相关性的证据，我们最近表明，工程致病株高表达 IFNγ 能减轻这种病毒。推理 IFNγ 表达式由株疫苗会提高其安全性和有效性，我们反向工程两个证明疫苗载体，气体和换热，来表达小鼠 IFNγ。死亡率和发病率在监测下进行哺乳小鼠感染、 免疫接种的挑战实验和混合的颅内感染。我们证明了 GASγ 和 GASγGAS 明显减毒的乳鼠相比换热疫苗。GASγ 更好地保护小鼠免受致命 DRV4 株感染相比换热的实验前和暴露后。最后，GASγGAS 可以减少感染后神经系统后遗症，相比控制，期间 DRV4 混合颅内感染。这些数据表明 IFNγ 表达的疫苗载体可以提高其安全同时增加其作为前和暴露后治疗的疗效。

結果 (中文) 3:

利用干扰素γ的表达增强了减毒狂犬病疫苗的前、后安全性和有效性。巴克豪斯DA，麦嘉华m，Hooper直流。摘要与干扰素-γ强相关的证据相一致（IFNγ）生产狂犬病病毒（RABV）从中枢神经系统的间隙，我们最近表明，工程是由表达IFN-γ高致病性减弱的病毒。推理，狂犬病疫苗γ表达干扰素会增强他们的安全性和有效性，我们进行反向工程两证明疫苗载体，天然气和煤气，表达小鼠IFN-γγ。发病率和死亡率在乳鼠感染的监测、免疫/挑战实验和混合颅内感染。我们表明，气γ气γ气明显抑制乳鼠相比，可疫苗。气γ更好的保护从致命的drv4 RABV感染小鼠前和暴露后的实验相比，可。最后，气γ气减少感染后神经系统后遗症，与对照相比，混合颅内感染drv4期间。这些数据表明，干扰素γ的表达的疫苗载体，可以提高其安全性，同时增加了其作为前和后曝光治疗的疗效。