Wang Yi-Xuan, Yang Guang-Hui, Zhang Lin-Lin, Wang Jing, Wang Jiu-Feng
College of Veterinary Medicine, China Agricultural University, Beijing 100193, China.
Vaccines (Basel). 2021 Sep 18;9(9):1039. doi: 10.3390/vaccines9091039.
Bovine viral diarrhea virus (BVDV) is a pathogen associated with substantial economic losses in the dairy cattle industry. Currently, there are no effective vaccines against BVDV. Melatonin (MT) has been shown to have anti-inflammatory and anti-viral properties, and the use of MF59 in vaccines significantly enhances vaccine efficiency. Here, MT and MF59 were added into the E-LTB vaccine. Subsequently, their inhibitory activity on the NF-κB signaling pathway in Mardin-Darby Bovine Kidney cells and the hippocampus was assessed using western blot and quantitative reverse transcription PCR. The findings revealed that MT in the E-LTB vaccine decreases the phosphorylation of p65 proteins caused by BVDV infection. In addition, MT decreased the mRNA levels of IL-1β and IL-6 in vitro, but increased the production of IFN-α, IFN-β, Mx1 in vitro, brain-derived neurotrophic factor, cyclic amp response element-binding protein, and the stem cell factor in vivo. Furthermore, treatment with E-LTB + MF59 + MT stimulated the production of T lymphocytes, alleviated pathological damage, decreased expressions of BVDV antigen, and tight junction proteins in mice. These findings imply that MT has potential for use in the E-LTB vaccine to inhibit BVDV infection and regulate the immune responses of T-cells by inhibiting the NF-κB signaling pathway.
牛病毒性腹泻病毒（BVDV）是一种给奶牛养殖业带来巨大经济损失的病原体。目前，尚无针对BVDV的有效疫苗。褪黑素（MT）已被证明具有抗炎和抗病毒特性，并且在疫苗中使用MF59可显著提高疫苗效率。在此，将MT和MF59添加到E-LTB疫苗中。随后，使用蛋白质免疫印迹法和定量逆转录PCR评估它们对马尔堡-达比牛肾细胞和海马体中NF-κB信号通路的抑制活性。研究结果显示，E-LTB疫苗中的MT可降低由BVDV感染引起的p65蛋白磷酸化水平。此外，MT在体外降低了IL-1β和IL-6的mRNA水平，但在体外增加了IFN-α、IFN-β、Mx1的产生，在体内增加了脑源性神经营养因子、环磷腺苷反应元件结合蛋白和干细胞因子的产生。此外，用E-LTB + MF59 + MT处理可刺激小鼠T淋巴细胞的产生，减轻病理损伤，降低BVDV抗原和紧密连接蛋白的表达。这些发现表明，MT有潜力用于E-LTB疫苗，以抑制BVDV感染并通过抑制NF-κB信号通路调节T细胞的免疫反应。
