Ultrapotent Human Neutralizing Antibody Repertoires Against Middle East Respiratory Syndrome Coronavirus From a Recovered Patient

被引：49

作者：

Niu, Peihua ^{[1
]}

Zhang, Senyan ^{[2
]}

Zhou, Panpan ^{[2
]}

Huang, Baoying ^{[1
]}

Deng, Yao ^{[1
]}

Qin, Kun ^{[1
]}

Wang, Pengfei ^{[2
]}

Wang, Wenling ^{[1
]}

Wang, Xinquan ^{[2
]}

Zhou, Jianfang ^{[1
]}

Zhang, Linqi ^{[2
]}

Tan, Wenjie ^{[1
]}

机构：

[1] Chinese Ctr Dis Control & Prevent, Natl Inst Viral Dis Control & Prevent, MOH Key Lab Med Virol, Beijing, Peoples R China

[2] Tsinghua Univ, Beijing Adv Innovat Ctr Struct Biol, Sch Life Sci, Minist Educ,Key Lab Prot Sci,Collaborat Innovat C, Beijing, Peoples R China

来源：

JOURNAL OF INFECTIOUS DISEASES | 2018年 / 218卷 / 08期

关键词：

crystallographic analysis; human monoclonal antibody; MERS-CoV; neutralizing antibody repertoires; HUMAN MONOCLONAL-ANTIBODIES; RECEPTOR-BINDING DOMAIN; MERS-COV; SPIKE PROTEIN; SAUDI-ARABIA; POSTEXPOSURE EFFICACY; DETERMINANTS; EVOLUTION; SOFTWARE; ANTIGEN;

D O I：

10.1093/infdis/jiy311

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Background. The Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe respiratory infection with a high (similar to 35%) mortality rate. Neutralizing antibodies targeting the spike of MERS-CoV have been shown to be a therapeutic option for treatment of lethal disease. Methods. We describe the germline diversity and neutralizing activity of 13 potent human monoclonal antibodies (mAbs) that target the MERS-CoV spike (S) protein. Biological functions were assessed by live MERS-CoV, pseudotype particle and its variants, and structural basis was also determined by crystallographic analysis. Results. Of the 13 mAbs displaying strong neutralizing activity against MERS-CoV, two with the immunoglobulin heavy-chain variable region (IGHV) 1-69-derived heavy chain (named MERS-GD27 and MERS-GD33) showed the most potent neutralizing activity against pseudotyped and live MERS-CoV in vitro. Mutagenesis analysis suggested that MERS-GD27 and MERS-GD33 recognized distinct regions in S glycoproteins, and the combination of 2 mAbs demonstrated a synergistic effect in neutralization against pseudotyped MERS-CoV. The structural basis of MERS-GD27 neutralization and recognition revealed that its epitope almost completely overlapped with the receptor-binding site. Conclusions. Our data provide new insights into the specific antibody repertoires and the molecular determinants of neutralization during natural MERS-CoV infection in humans. This finding supports additional efforts to design and develop novel therapies to combat MERS-CoV infections in humans.

引用

页码：1249 / 1260

页数：12

共 42 条

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