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Human monoclonal antibodies against highly conserved HR1 and HR2 domains of the SARS-CoV spike protein are more broadly neutralizing
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 (...
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Published in: | PloS one 2012-11, Vol.7 (11), p.e50366-e50366 |
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description | 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. |
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subjects | Amino acids Antibodies, Neutralizing - pharmacology Antibodies, Viral - pharmacology Antibody Affinity Antibody Specificity Binding Binding Sites, Antibody Biology Cell growth Clinical isolates Cloning Cross Reactions Epitope Mapping Glycoproteins Health aspects HEK293 Cells Humans Immune serum Immunoglobulins Immunology Immunotherapy Infections Laboratories Medicine Membrane Glycoproteins - antagonists & inhibitors Membrane Glycoproteins - genetics Membrane Glycoproteins - immunology Monoclonal antibodies Mutagenesis Neutralization Tests Neutralizing Patients Plasmids Protein Binding Protein Structure, Tertiary Proteins Recombinant Proteins - antagonists & inhibitors Recombinant Proteins - genetics Recombinant Proteins - immunology SARS Virus - drug effects SARS Virus - genetics SARS Virus - immunology Severe acute respiratory syndrome Severe Acute Respiratory Syndrome - immunology Severe Acute Respiratory Syndrome - prevention & control Spike Glycoprotein, Coronavirus Spike protein Transfection Vaccines Viral Envelope Proteins - antagonists & inhibitors Viral Envelope Proteins - genetics Viral Envelope Proteins - immunology Viruses |
title | Human monoclonal antibodies against highly conserved HR1 and HR2 domains of the SARS-CoV spike protein are more broadly neutralizing |
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