Institute for Virology, University Hospital Essen, University Duisburg-Essen, Essen, Germany.
Division of Pharmacovigilance, Paul-Ehrlich-Institut, Langen, Germany.
PLoS One. 2013 Dec 4;8(12):e82528. doi: 10.1371/journal.pone.0082528. eCollection 2013.
Interleukins (IL) are cytokines with stimulatory and modulatory functions in the immune system. In this study, we have chosen interleukins which are involved in the enhancement of TH2 responses and B cell functions to analyze their potential to improve a prophylactic adenovirus-based anti-retroviral vaccine with regard to antibody and virus-specific CD4(+) T cell responses. Mice were vaccinated with an adenoviral vector which encodes and displays the Friend Virus (FV) surface envelope protein gp70 (Ad.pIXgp70) in combination with adenoviral vectors encoding the interleukins IL4, IL5, IL6, IL7 or IL23. Co-application of Ad.pIXgp70 with Ad.IL5, Ad.IL6 or Ad.IL23 resulted in improved protection with high control over FV-induced splenomegaly and reduced viral loads. Mice co-immunized with adenoviral vectors encoding IL5 or IL23 showed increased neutralizing antibody responses while mice co-immunized with Ad.IL6 or Ad.IL23 showed improved FV-specific CD4(+) T cell responses compared to mice immunized with Ad.pIXgp70 alone. We show that the co-application of adenoviral vectors encoding specific interleukins is suitable to improve the vaccination efficacy of an anti-retroviral vaccine. Improved protection correlated with improved CD4(+) T cell responses and especially with higher neutralizing antibody titers. The co-application of selected interleukin-encoding adenoviral vectors is a valuable tool for vaccination with regard to enhancement of antibody mediated immunity.
白细胞介素 (IL) 是具有免疫刺激和调节功能的细胞因子。在这项研究中，我们选择了参与增强 TH2 反应和 B 细胞功能的白细胞介素，以分析它们在改善基于腺病毒的抗逆转录病毒疫苗方面的潜力，该疫苗针对抗体和病毒特异性 CD4(+) T 细胞反应。用编码和显示 Friend 病毒 (FV) 表面包膜蛋白 gp70 的腺病毒载体（Ad.pIXgp70）与编码白细胞介素 IL4、IL5、IL6、IL7 或 IL23 的腺病毒载体联合对小鼠进行疫苗接种。将 Ad.pIXgp70 与 Ad.IL5、Ad.IL6 或 Ad.IL23 共同应用可改善保护作用，高度控制 FV 诱导的脾肿大和降低病毒载量。与单独用 Ad.pIXgp70 免疫的小鼠相比，用编码 IL5 或 IL23 的腺病毒载体共同免疫的小鼠显示出增加的中和抗体反应，而用 Ad.IL6 或 Ad.IL23 共同免疫的小鼠显示出改善的 FV 特异性 CD4(+) T 细胞反应。我们表明，编码特定白细胞介素的腺病毒载体的共同应用适合于改善抗逆转录病毒疫苗的接种效果。改善的保护作用与改善的 CD4(+) T 细胞反应相关，尤其是与更高的中和抗体滴度相关。选择的白细胞介素编码腺病毒载体的共同应用是增强抗体介导免疫的疫苗接种的有价值工具。
