title: Human monoclonal antibodies against highly conserved HR1 and HR2 domains of the SARS-CoV spike protein are more broadly neutralizing.
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 generating therapeutic antibodies or subunit vaccines against other enveloped viruses.
authors.affiliation: Department of Microbiology and Immunology, College of Medicine, University of Illinois at Chicago, Chicago, Illinois, United States of America.
authors.forename: Hatem A
authors.initials: HA
authors.lastname: Elshabrawy
authors.forename: Melissa M
authors.initials: MM
authors.lastname: Coughlin
authors.forename: Susan C
authors.initials: SC
authors.lastname: Baker
authors.forename: Bellur S
authors.initials: BS
authors.lastname: Prabhakar
mesh_terms: D057134:Antibodies, Neutralizing / Q000494:pharmacology*; D000914:Antibodies, Viral / Q000494:pharmacology*; D000915:Antibody Affinity; D000918:Antibody Specificity; D001666:Binding Sites, Antibody; D003429:Cross Reactions; D018604:Epitope Mapping; D057809:HEK293 Cells; D006801:Humans; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000276:immunology; D009500:Neutralization Tests; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology; D045473:Severe acute respiratory syndrome-related coronavirus / Q000187:drug effects* / Q000235:genetics / Q000276:immunology; D045169:Severe Acute Respiratory Syndrome / Q000276:immunology / Q000517:prevention & control; D064370:Spike Glycoprotein, Coronavirus; D014162:Transfection; D014759:Viral Envelope Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000276:immunology
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D008562:Membrane Glycoproteins; D011994:Recombinant Proteins; D064370:Spike Glycoprotein, Coronavirus; D014759:Viral Envelope Proteins; C578557:spike glycoprotein, SARS-CoV; C578553:spike protein, mouse hepatitis virus