human monoclonal antibodies against highly conserved hr1 and hr2 domains of the sars-cov spike protein are more broadly neutralizing人类单克隆抗体高度保守的hr1上和冠状突起蛋白的hr2领域更广泛的中和.pdfVIP

Human Monoclonal Antibodies against Highly Conserved HR1 and HR2 Domains of the SARS-CoV Spike Protein Are More Broadly Neutralizing 1 2 3 1 Hatem A. Elshabrawy , Melissa M. Coughlin , Susan C. Baker , Bellur S. Prabhakar * 1 Department of Microbiology and Immunology, College of Medicine, University of Illinois at Chicago, Chicago, Illinois, United States of America, 2 Centers for Disease Control and Prevention, Measles, Mumps, Rubella and Herpes Virus Laboratory Branch, Atlanta, Georgia, United States of America, 3 Department of Microbiology and Immunology, Loyola University Chicago Stritch School of Medicine, Maywood, Illinois, United States of America Abstract Immune sera from convalescent patients have been shown to be effective in the treatment of patients infected with Severe Acute Respiratory Syndrome Virus (SARS-CoV) making passive immune therapy with human monoclonal antibodies an attractive treatment strategy for SARS. Previously, using Xenomouse (Amgen British Columbia Inc), we produced a panel of neutralizing Human monoclonal antibodies (HmAbs) that could specifically bind to the ectodomain of the SARS-CoV spike (S) glycoprotein. Some of the HmAbs were S1 domain specific, while some were not. In this study, we describe non-S1 binding neutralizing HmAbs that can specifically bind to the conserved S2 domain of the S protein. However, unlike the S1 specific HmAbs, the S2 specific HmAbs can neutralize pseudotyped viruses expressing different S proteins containing receptor binding domain sequences of various clinical isolates. These data indicate that HmAbs which bind to conserved regions of the S protein are more suitable for conferring protection against a wide range of SARS-CoV variants and have implications for