Use of a recombinant vaccinia virus expressing interferon gamma for post-exposure protection against vaccinia and ectromelia viruses.
Use of a recombinant vaccinia virus expressing interferon gamma for post-exposure protection against vaccinia and ectromelia viruses.
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DOI：
10.1371/journal.pone.0077879
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Jacobs BL
中科院分区：
文献类型：
--
作者：
Holechek SA;Denzler KL;Heck MC;Schriewer J;Buller RM;Legrand FA;Verardi PH;Jones LA;Yilma T;Jacobs BL
暴露后接种牛痘病毒（VACV）被认为是有效的，如果在天花暴露后四天内接种，可以最大限度地减少死亡。虽然有轶事证据表明暴露后接种疫苗的有效性，但尚未在人类中进行明确研究。在这项研究中，我们分析了暴露后预防使用几个减毒重组VACV在小鼠模型。表达鼠干扰素γ（IFN-γ）的重组VACV对VACV和ECTV感染的小鼠的暴露后保护作用最有效。感染VACV的未治疗动物表现出严重的体重减轻和发病率，导致感染后8至10天的100%死亡率。感染后一天治疗的动物症状较轻，体重减轻和发病率降低，100%存活。感染后第2天或第3天的治疗分别导致40%和20%的存活率。在ECTV感染的小鼠中也观察到类似的结果。尽管VACV模型中的存活率存在差异，但治疗和未治疗小鼠的病毒载量相似，而治疗小鼠的血清中显示出高水平的IFN-γ。这些结果表明，由VACV表达的IFN-γ提供的保护可能是由其免疫调节活性介导的，而不是其抗病毒作用。这些结果强调了IFN-γ作为暴露后预防免疫应答调节剂的重要性，并可能用作另一种暴露后预防工具，以预防天花和其他正痘病毒感染后的发病率。
Post-exposure vaccination with vaccinia virus (VACV) has been suggested to be effective in minimizing death if administered within four days of smallpox exposure. While there is anecdotal evidence for efficacy of post-exposure vaccination this has not been definitively studied in humans. In this study, we analyzed post-exposure prophylaxis using several attenuated recombinant VACV in a mouse model. A recombinant VACV expressing murine interferon gamma (IFN-γ) was most effective for post-exposure protection of mice infected with VACV and ectromelia virus (ECTV). Untreated animals infected with VACV exhibited severe weight loss and morbidity leading to 100% mortality by 8 to 10 days post-infection. Animals treated one day post-infection had milder symptoms, decreased weight loss and morbidity, and 100% survival. Treatment on days 2 or 3 post-infection resulted in 40% and 20% survival, respectively. Similar results were seen in ECTV-infected mice. Despite the differences in survival rates in the VACV model, the viral load was similar in both treated and untreated mice while treated mice displayed a high level of IFN-γ in the serum. These results suggest that protection provided by IFN-γ expressed by VACV may be mediated by its immunoregulatory activities rather than its antiviral effects. These results highlight the importance of IFN-γ as a modulator of the immune response for post-exposure prophylaxis and could be used potentially as another post-exposure prophylaxis tool to prevent morbidity following infection with smallpox and other orthopoxviruses.
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