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Single-dose treatment with a humanized neutralizing antibody affords full protection of a human transgenic mouse model from lethal Middle East respiratory syndrome (MERS)-coronavirus infection.
Antiviral Res. 2016 08; 132:141-8.AR

Abstract

Middle East respiratory syndrome coronavirus (MERS-CoV) is continuously spreading and causing severe and fatal acute respiratory disease in humans. Prophylactic and therapeutic strategies are therefore urgently needed to control MERS-CoV infection. Here, we generated a humanized monoclonal antibody (mAb), designated hMS-1, which targeted the MERS-CoV receptor-binding domain (RBD) with high affinity. hMS-1 significantly blocked MERS-CoV RBD binding to its viral receptor, human dipeptidyl peptidase 4 (hDPP4), potently neutralized infection by a prototype MERS-CoV, and effectively cross-neutralized evolved MERS-CoV isolates through recognizing highly conserved RBD epitopes. Notably, single-dose treatment with hMS-1 completely protected hDPP4 transgenic (hDPP4-Tg) mice from lethal infection with MERS-CoV. Taken together, our data suggest that hMS-1 might be developed as an effective immunotherapeutic agent to treat patients infected with MERS-CoV, particularly in emergent cases.

Authors+Show Affiliations

State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China.State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China.Beijing Institute of Basic Medical Sciences, Beijing, China.Beijing Institute of Basic Medical Sciences, Beijing, China.State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China.State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China; Lindsley F. Kimball Research Institute, New York Blood Center, New York, NY, USA.State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China; Lindsley F. Kimball Research Institute, New York Blood Center, New York, NY, USA.Lindsley F. Kimball Research Institute, New York Blood Center, New York, NY, USA.State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China. Electronic address: guangyu0525@163.com.State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China. Electronic address: yszhou@bmi.ac.cn.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

27312105

Citation

Qiu, Hongjie, et al. "Single-dose Treatment With a Humanized Neutralizing Antibody Affords Full Protection of a Human Transgenic Mouse Model From Lethal Middle East Respiratory Syndrome (MERS)-coronavirus Infection." Antiviral Research, vol. 132, 2016, pp. 141-8.
Qiu H, Sun S, Xiao H, et al. Single-dose treatment with a humanized neutralizing antibody affords full protection of a human transgenic mouse model from lethal Middle East respiratory syndrome (MERS)-coronavirus infection. Antiviral Res. 2016;132:141-8.
Qiu, H., Sun, S., Xiao, H., Feng, J., Guo, Y., Tai, W., Wang, Y., Du, L., Zhao, G., & Zhou, Y. (2016). Single-dose treatment with a humanized neutralizing antibody affords full protection of a human transgenic mouse model from lethal Middle East respiratory syndrome (MERS)-coronavirus infection. Antiviral Research, 132, 141-8. https://doi.org/10.1016/j.antiviral.2016.06.003
Qiu H, et al. Single-dose Treatment With a Humanized Neutralizing Antibody Affords Full Protection of a Human Transgenic Mouse Model From Lethal Middle East Respiratory Syndrome (MERS)-coronavirus Infection. Antiviral Res. 2016;132:141-8. PubMed PMID: 27312105.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Single-dose treatment with a humanized neutralizing antibody affords full protection of a human transgenic mouse model from lethal Middle East respiratory syndrome (MERS)-coronavirus infection. AU - Qiu,Hongjie, AU - Sun,Shihui, AU - Xiao,He, AU - Feng,Jiannan, AU - Guo,Yan, AU - Tai,Wanbo, AU - Wang,Yufei, AU - Du,Lanying, AU - Zhao,Guangyu, AU - Zhou,Yusen, Y1 - 2016/06/14/ PY - 2016/03/30/received PY - 2016/05/19/revised PY - 2016/06/12/accepted PY - 2016/6/18/entrez PY - 2016/6/18/pubmed PY - 2017/11/29/medline KW - Humanized monoclonal antibody KW - Lethal infection KW - MERS-CoV KW - Protection KW - Receptor-binding domain KW - Treatment SP - 141 EP - 8 JF - Antiviral research JO - Antiviral Res VL - 132 N2 - Middle East respiratory syndrome coronavirus (MERS-CoV) is continuously spreading and causing severe and fatal acute respiratory disease in humans. Prophylactic and therapeutic strategies are therefore urgently needed to control MERS-CoV infection. Here, we generated a humanized monoclonal antibody (mAb), designated hMS-1, which targeted the MERS-CoV receptor-binding domain (RBD) with high affinity. hMS-1 significantly blocked MERS-CoV RBD binding to its viral receptor, human dipeptidyl peptidase 4 (hDPP4), potently neutralized infection by a prototype MERS-CoV, and effectively cross-neutralized evolved MERS-CoV isolates through recognizing highly conserved RBD epitopes. Notably, single-dose treatment with hMS-1 completely protected hDPP4 transgenic (hDPP4-Tg) mice from lethal infection with MERS-CoV. Taken together, our data suggest that hMS-1 might be developed as an effective immunotherapeutic agent to treat patients infected with MERS-CoV, particularly in emergent cases. SN - 1872-9096 UR - https://www.unboundmedicine.com/medline/citation/27312105/Single_dose_treatment_with_a_humanized_neutralizing_antibody_affords_full_protection_of_a_human_transgenic_mouse_model_from_lethal_Middle_East_respiratory_syndrome__MERS__coronavirus_infection_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0166-3542(16)30191-7 DB - PRIME DP - Unbound Medicine ER -