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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
Main Authors: Elshabrawy, Hatem A, Coughlin, Melissa M, Baker, Susan C, Prabhakar, Bellur S
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cited_by cdi_FETCH-LOGICAL-c758t-3701f2a0c4cad0ed6fe7a54adda56695198402449931d1d3f215532b79cdcd1a3
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Prabhakar, Bellur S
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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1932-6203
language eng
recordid cdi_plos_journals_1326749386
source Publicly Available Content (ProQuest); PubMed Central; Coronavirus Research Database
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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