Ultrapotent Human Neutralizing Antibody Repertoires Against Middle East Respiratory Syndrome Coronavirus From a Recovered Patient. (28th May 2018)

• Record Type: Journal Article
• Authors: Niu, Peihua; Zhang, Senyan; Zhou, Panpan; Huang, Baoying; Deng, Yao; Qin, Kun; Wang, Pengfei; Wang, Wenling; Wang, Xinquan; Zhou, Jianfang; Zhang, Linqi; Tan, Wenjie
• Is Part Of: Journal of infectious diseases. Volume 218:Number 8(2018)
• Page Start: 1249
• Page End: 1260
• Publication Date: 2018-05-28
• Subjects: crystallographic analysis -- human monoclonal antibody -- MERS-CoV -- neutralizing antibody repertoires; Communicable diseases -- Periodicals; Diseases -- Causes and theories of causation -- Periodicals; Medicine -- Periodicals; Communicable Diseases -- Periodicals; Electronic journals; 616.9
• DOI: 10.1093/infdis/jiy311
• Languages: English
• ISSNs: 0022-1899

Abstract

Abstract : We describe the MERS-CoV-neutralizing antibody repertoires from a survivor and characterized 13 ultrapotent mAbs. The mAbs, MERS-GD27 and MERS-GD33, exhibited the strongest neutralizing activities. Both targeted receptor-binding domain via different contacts. The epitopes of MERS-GD27 overlapped with DPP4-binding sites. Abstract: Background: The Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe respiratory infection with a high (~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.