Department of Molecular and Medical Virology, Institute of Microbiology and Hygiene, Ruhr-University Bochum, Germany.
Retrovirology. 2011 Sep 26;8:75. doi: 10.1186/1742-4690-8-75.
Type I interferons (IFNs) exhibit direct antiviral effects, but also distinct immunomodulatory properties. In this study, we analyzed type I IFN subtypes for their effect on prophylactic adenovirus-based anti-retroviral vaccination of mice against Friend retrovirus (FV) or HIV.
Mice were vaccinated with adenoviral vectors encoding FV Env and Gag proteins alone or in combination with vectors encoding IFNα1, IFNα2, IFNα4, IFNα5, IFNα6, IFNα9 or IFNβ. Only the co-administration of adenoviral vectors encoding IFNα2, IFNα4, IFNα6 and IFNα9 resulted in strongly improved immune protection of vaccinated mice from subsequent FV challenge infection with high control over FV-induced splenomegaly and reduced viral loads. The level of protection correlated with augmented virus-specific CD4(+) T cell responses and enhanced antibody titers. Similar results were obtained when mice were vaccinated against HIV with adenoviral vectors encoding HIV Env and Gag-Pol in combination with various type I IFN encoding vectors. Here mainly CD4(+) T cell responses were enhanced by IFNα subtypes.
Our results indicate that certain IFNα subtypes have the potential to improve the protective effect of adenovirus-based vaccines against retroviruses. This correlated with augmented virus-specific CD4(+) T cell and antibody responses. Thus, co-expression of select type I IFNs may be a valuable tool for the development of anti-retroviral vaccines.
I 型干扰素（IFN）具有直接抗病毒作用，同时具有独特的免疫调节特性。在这项研究中，我们分析了 I 型 IFN 亚型对预防型腺病毒抗逆转录病毒疫苗接种预防 Friend 逆转录病毒（FV）或 HIV 的作用。
用编码 FV Env 和 Gag 蛋白的腺病毒载体单独或与编码 IFNα1、IFNα2、IFNα4、IFNα5、IFNα6、IFNα9 或 IFNβ的载体联合对小鼠进行疫苗接种。只有共施用编码 IFNα2、IFNα4、IFNα6 和 IFNα9 的腺病毒载体可显著增强疫苗接种小鼠对随后的 FV 攻毒感染的免疫保护，对 FV 引起的脾肿大和降低病毒载量具有高度控制作用。保护水平与增强的病毒特异性 CD4(+)T 细胞反应和增强的抗体滴度相关。当用编码 HIV Env 和 Gag-Pol 的腺病毒载体与各种编码 I 型 IFN 的载体联合对小鼠进行 HIV 疫苗接种时，获得了类似的结果。这里主要是通过 IFNα 亚型增强了 CD4(+)T 细胞反应。
我们的结果表明，某些 IFNα 亚型有可能提高基于腺病毒的抗逆转录病毒疫苗的保护作用。这与增强的病毒特异性 CD4(+)T 细胞和抗体反应相关。因此，选择的 I 型 IFN 的共表达可能是开发抗逆转录病毒疫苗的有价值的工具。
