National Engineering Research Center for Bioengineering Drugs and the Technologies, Institute of Translational Medicine, Nanchang University, Nanchang, China.
JiangXi University of Traditional Chinese Medicine, College of Basic Medicine, Nanchang, China.
Front Cell Infect Microbiol. 2019 Jul 31;9:275. doi: 10.3389/fcimb.2019.00275. eCollection 2019.
Respiratory syncytial virus (RSV) is the major cause of pulmonary and bronchial inflammation in infants, young children, and immunocompromised adults, but therapeutic options to control RSV are limited. In the present study a single chain antibody against RSV (GD-scFv) was screened using phage display library panning technology and a full-length monoclonal antibody (GD-mAb) was developed from GD-scFv based on the sequence encoding Ig V and Ig V. The anti-RSV potential of GD-mAb was evaluated and in mice. Our results indicated that both GD-scFv (4.25 ± 2 nM) and GD-mAb (3.13 ± 0.89 nM) showed high binding capability and strong binding specificity to GD protein. GD-mAb effectively neutralized RSV and reduced the plaque number in a concentration-dependent manner through a plaque reduction neutralization assay. In mice, GD-mAb lowered the lung index and reduced the lung virus titer in the mouse lung ( < 0.05). Antibody treatment reduced the phosphorylated protein level in pathways of TLR4/NF-κB, MAPKs, and PI3K/Akt ( < 0.05) and correlated with an absence of pro-inflammatory factors TNF-α, IL-1β, and IL-6 in the mouse lung and serum ( < 0.05). In summary, these data suggest that GD-mAb may be an effective therapeutic agent for the treatment of RSV infections. Currently, only a few therapeutic options are available to control respiratory RSV in humans. In this study, our group developed a full-length monoclonal antibody (GD-mAb) and reported a high binding specificity of the RSV surface glycoproteins G. Moreover, GD-mAb effectively neutralized RSV , and significantly lowered the lung index and reduced the lung virus titer in an infected mouse lung, which suggests that GD-mAb may serve as an effective antiviral agent for RSV infection.
呼吸道合胞病毒（RSV）是婴儿、幼儿和免疫功能低下的成年人肺部和支气管炎症的主要原因，但控制 RSV 的治疗选择有限。在本研究中，使用噬菌体展示文库淘选技术筛选出针对 RSV 的单链抗体（GD-scFv），并根据编码 Ig V 和 Ig V 的序列从 GD-scFv 开发出全长单克隆抗体（GD-mAb）。在小鼠中评估了 GD-mAb 针对 RSV 的潜力。我们的结果表明，GD-scFv（4.25 ± 2 nM）和 GD-mAb（3.13 ± 0.89 nM）均表现出对 GD 蛋白的高结合能力和强结合特异性。GD-mAb 通过蚀斑减少中和试验有效中和 RSV，并呈浓度依赖性降低蚀斑数量。在小鼠中，GD-mAb 降低了肺指数，并降低了小鼠肺中的肺病毒滴度（<0.05）。抗体治疗降低了 TLR4/NF-κB、MAPKs 和 PI3K/Akt 通路中磷酸化蛋白的水平（<0.05），并与小鼠肺和血清中促炎因子 TNF-α、IL-1β 和 IL-6 的缺失相关（<0.05）。总之，这些数据表明 GD-mAb 可能是治疗 RSV 感染的有效治疗剂。
目前，只有少数治疗选择可用于控制人类呼吸道 RSV。在这项研究中，我们小组开发了一种全长单克隆抗体（GD-mAb），并报道了 RSV 表面糖蛋白 G 的高结合特异性。此外，GD-mAb 有效中和了 RSV，并显著降低了感染小鼠肺部的肺指数和降低了肺部病毒滴度，这表明 GD-mAb 可能是 RSV 感染的有效抗病毒药物。
