Tags

Type your tag names separated by a space and hit enter

Preparation and Evaluation of the Fully Humanized Monoclonal Antibody GD-mAb Against Respiratory Syncytial Virus.

Abstract

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 VH and Ig VL. The anti-RSV potential of GD-mAb was evaluated in vitro 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 (p < 0.05). Antibody treatment reduced the phosphorylated protein level in pathways of TLR4/NF-κB, MAPKs, and PI3K/Akt (p < 0.05) and correlated with an absence of pro-inflammatory factors TNF-α, IL-1β, and IL-6 in the mouse lung and serum (p < 0.05). In summary, these data suggest that GD-mAb may be an effective therapeutic agent for the treatment of RSV infections. Importance 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 in vitro, 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.

Authors+Show Affiliations

National Engineering Research Center for Bioengineering Drugs and the Technologies, Institute of Translational Medicine, Nanchang University, Nanchang, China.National Engineering Research Center for Bioengineering Drugs and the Technologies, Institute of Translational Medicine, Nanchang University, Nanchang, China.National Engineering Research Center for Bioengineering Drugs and the Technologies, Institute of Translational Medicine, Nanchang University, Nanchang, China.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.State Key Laboratory of Food Science and Technology, Nanchang, China.National Engineering Research Center for Bioengineering Drugs and the Technologies, Institute of Translational Medicine, Nanchang University, Nanchang, China.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31417879

Citation

Tian, Puyuan, et al. "Preparation and Evaluation of the Fully Humanized Monoclonal Antibody GD-mAb Against Respiratory Syncytial Virus." Frontiers in Cellular and Infection Microbiology, vol. 9, 2019, p. 275.
Tian P, Wang Y, Liu H, et al. Preparation and Evaluation of the Fully Humanized Monoclonal Antibody GD-mAb Against Respiratory Syncytial Virus. Front Cell Infect Microbiol. 2019;9:275.
Tian, P., Wang, Y., Liu, H., Yang, Y., Wu, X., Wei, H., & Chen, T. (2019). Preparation and Evaluation of the Fully Humanized Monoclonal Antibody GD-mAb Against Respiratory Syncytial Virus. Frontiers in Cellular and Infection Microbiology, 9, p. 275. doi:10.3389/fcimb.2019.00275.
Tian P, et al. Preparation and Evaluation of the Fully Humanized Monoclonal Antibody GD-mAb Against Respiratory Syncytial Virus. Front Cell Infect Microbiol. 2019;9:275. PubMed PMID: 31417879.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Preparation and Evaluation of the Fully Humanized Monoclonal Antibody GD-mAb Against Respiratory Syncytial Virus. AU - Tian,Puyuan, AU - Wang,Yuqing, AU - Liu,Hui, AU - Yang,Yulu, AU - Wu,Xiaoli, AU - Wei,Hua, AU - Chen,Tingtao, Y1 - 2019/07/31/ PY - 2019/02/08/received PY - 2019/07/17/accepted PY - 2019/8/17/entrez PY - 2019/8/17/pubmed PY - 2019/8/17/medline KW - inflammation KW - monoclonal antibody KW - phage display technology KW - respiratory syncytial virus (RSV) KW - signal pathway SP - 275 EP - 275 JF - Frontiers in cellular and infection microbiology JO - Front Cell Infect Microbiol VL - 9 N2 - 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 VH and Ig VL. The anti-RSV potential of GD-mAb was evaluated in vitro 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 (p < 0.05). Antibody treatment reduced the phosphorylated protein level in pathways of TLR4/NF-κB, MAPKs, and PI3K/Akt (p < 0.05) and correlated with an absence of pro-inflammatory factors TNF-α, IL-1β, and IL-6 in the mouse lung and serum (p < 0.05). In summary, these data suggest that GD-mAb may be an effective therapeutic agent for the treatment of RSV infections. Importance 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 in vitro, 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. SN - 2235-2988 UR - https://www.unboundmedicine.com/medline/citation/31417879/Preparation_and_Evaluation_of_the_Fully_Humanized_Monoclonal_Antibody_GD-mAb_Against_Respiratory_Syncytial_Virus L2 - https://doi.org/10.3389/fcimb.2019.00275 DB - PRIME DP - Unbound Medicine ER -