State Key Laboratory of Veterinary Etiological Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences (CAAS), Lanzhou, 730046, China.
Appl Microbiol Biotechnol. 2017 Nov;101(21):7889-7900. doi: 10.1007/s00253-017-8523-y. Epub 2017 Sep 19.
Targeting antigen to dendritic cells (DCs) is a promising way to manipulate the immune response and to design prophylactic molecular vaccines. In this study, the cattle XCL1, ligand of XCR1, was fused to the type O foot-and-mouth disease virus (FMDV) multi-epitope protein (XCL-OB7) to create a molecular vaccine antigen, and an XCL-OB7 protein with a mutation in XCL1 was used as the control. XCL-OB7 protein specifically bound to the XCR1 receptor, as detected by flow cytometry. Cattle vaccinated with XCL-OB7 showed a significantly higher antibody response than that to the XCL-OB7 control (P < 0.05). In contrast, when XCL-OB7 was incorporated with poly (I:C) to prepare the vaccine, the antibody response of the immunized cattle was significantly decreased in this group and was lower than that in the XCL-OB7 plus poly (I:C) group. The FMDV challenge indicated that cattle immunized with the XCL-OB7 alone or the XCL-OB7 plus poly (I:C) obtained an 80% (4/5) clinical protective rate. However, cattle vaccinated with XCL-OB7 plus poly (I:C) showed more effective inhibition of virus replication than that in the XCL-OB7 group after viral challenge, according to the presence of antibodies against FMDV non-structural protein 3B. This is the first test of DC-targeted vaccines in veterinary medicine to use XCL1 fused to FMDV antigens. This primary result showed that an XCL1-based molecular vaccine enhanced the antibody response in cattle. This knowledge should be valuable for the development of antibody-dependent vaccines for some infectious diseases in cattle.
针对树突状细胞(DCs)的靶向是一种很有前途的操纵免疫反应和设计预防性分子疫苗的方法。在这项研究中,牛 XCL1(XCR1 的配体)与口蹄疫病毒(FMDV)多表位蛋白(XCL-OB7)融合,创造了一种分子疫苗抗原,并用 XCL1 突变的 XCL-OB7 蛋白作为对照。XCL-OB7 蛋白通过流式细胞术检测特异性结合 XCR1 受体。牛接种 XCL-OB7 后,抗体反应明显高于 XCL-OB7 对照组(P < 0.05)。相比之下,当 XCL-OB7 与聚(I:C)结合制备疫苗时,免疫牛的抗体反应在该组显著下降,低于 XCL-OB7 加聚(I:C)组。FMDV 攻毒表明,单独接种 XCL-OB7 或 XCL-OB7 加聚(I:C)的牛获得了 80%(4/5)的临床保护率。然而,在病毒攻毒后,与 XCL-OB7 组相比,接种 XCL-OB7 加聚(I:C)的牛表现出更有效的病毒复制抑制作用,根据其对 FMDV 非结构蛋白 3B 的抗体存在情况。这是首次在兽医中使用融合 FMDV 抗原的 DC 靶向疫苗进行的测试。这一初步结果表明,基于 XCL1 的分子疫苗增强了牛的抗体反应。这一知识对于开发一些牛传染性疾病的抗体依赖性疫苗应该是有价值的。