Alpha interferon as an adenovirus-vectored vaccine adjuvant and antiviral in Venezuelan equine encephalitis virus infection
Alpha interferon as an adenovirus-vectored vaccine adjuvant and antiviral in Venezuelan equine encephalitis virus infection
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DOI：
10.1099/vir.0.006833-0
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发表时间：
2009-04-01
影响因子：
3.8
通讯作者：
Phillpotts, Robert
中科院分区：
文献类型：
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作者：
O'Brien, Lyn;Perkins, Stuart;Phillpotts, Robert
虽然一种表达委内瑞拉马脑炎病毒（VEEV）结构蛋白的腺病毒载体可以保护小鼠免受VEEV的攻击，并且可能是一种适合人类使用的疫苗，但目前还没有广泛可用的疫苗或抗病毒药物能够保护小鼠免受VEEV感染。这项工作研究了α干扰素（ifn - α）是否可以作为腺病毒疫苗的佐剂。ifn - α要么通过与腺病毒疫苗连接的质粒表达，要么通过与疫苗混合施用的单独腺病毒载体编码。与先前报道的其他疫苗相比，ifn - α的存在降低了对VEEV的抗体反应。当ifn - α被腺病毒编码时，veev特异性应答的缺乏伴随着对腺病毒载体的免疫应答的增加。ifn - α还在防御病毒感染中发挥直接作用，诱导大量抗病毒蛋白的表达。在攻击前24小时给药时，腺病毒递送的ifn - α可以保护小鼠免受VEEV疾病的侵袭，但在攻击后6小时给药时则不然，这表明ifn介导的抗病毒应答的发展需要多达24个In。
There are no widely available vaccines or antiviral drugs capable of protecting against infection with Venezuelan equine encephalitis virus (VEEV), although an adenovirus vector expressing VEEV structural proteins protects mice from challenge with VEEV and is potentially a vaccine suitable for human use. This work examines whether alpha interferon (IFN-alpha) could act as an adjuvant for the adenovirus-based vaccine. IFN-alpha was either expressed by a plasmid linked to the adenovirus vaccine or encoded by a separate adenovirus vector administered as a mixture with the vaccine. In contrast to previous reports with other vaccines, the presence of IFN-alpha reduced the antibody response to VEEV. When IFN-alpha was encoded by adenovirus, the lack of a VEEV-specific response was accompanied by an increase in the immune response to the adenovirus vector. IFN-alpha also plays a direct role in defence against virus infection, inducing the expression of a large number of antiviral proteins. Adenovirus-delivered IFN-alpha protected mice from VEEV disease when administered 24 In prior to challenge, but not when administered 6 h post-challenge, suggesting that up to 24 In is required for the development of the IFN-mediated antiviral response.