Document Detail


Generation and characterization of human monoclonal neutralizing antibodies with distinct binding and sequence features against SARS coronavirus using XenoMouse.
MedLine Citation:
PMID:  17161858     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Passive therapy with neutralizing human monoclonal antibodies (mAbs) could be an effective therapy against severe acute respiratory syndrome coronavirus (SARS-CoV). Utilizing the human immunoglobulin transgenic mouse, XenoMouse, we produced fully human SARS-CoV spike (S) protein specific antibodies. Antibodies were examined for reactivity against a recombinant S1 protein, to which 200 antibodies reacted. Twenty-seven antibodies neutralized 200TCID(50) SARS-CoV (Urbani). Additionally, 57 neutralizing antibodies were found that are likely specific to S2. Mapping of the binding region was achieved with several S1 recombinant proteins. Most S1 reactive neutralizing mAbs bound to the RBD, aa 318-510. However, two S1 specific mAbs reacted with a domain upstream of the RBD between aa 12 and 261. Immunoglobulin gene sequence analyses suggested at least 8 different binding specificities. Unique human mAbs could be used as a cocktail that would simultaneously target several neutralizing epitopes and prevent emergence of escape mutants.
Authors:
Melissa Coughlin; Gin Lou; Osvaldo Martinez; Stephanie K Masterman; Ole A Olsen; Angelica A Moksa; Michael Farzan; John S Babcook; Bellur S Prabhakar
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Publication Detail:
Type:  Journal Article     Date:  2006-12-11
Journal Detail:
Title:  Virology     Volume:  361     ISSN:  0042-6822     ISO Abbreviation:  Virology     Publication Date:  2007 Apr 
Date Detail:
Created Date:  2007-04-16     Completed Date:  2007-06-22     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0110674     Medline TA:  Virology     Country:  United States    
Other Details:
Languages:  eng     Pagination:  93-102     Citation Subset:  IM    
Affiliation:
Department of Microbiology and Immunology (MC790) College of Medicine, University of Illinois at Chicago, Room E705. 835 S. Wolcott AveChicago, IL 60612, USA.
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Sequence
Animals
Antibodies, Monoclonal / biosynthesis,  genetics,  immunology*
Antibodies, Viral / biosynthesis,  genetics,  immunology*
Antibody Specificity
Hemagglutinins, Viral / immunology
Humans
Hybridomas
Immunoglobulins / genetics,  metabolism
Membrane Glycoproteins / immunology
Mice
Mice, Transgenic
Molecular Sequence Data
Neutralization Tests
SARS Virus / immunology*
Sequence Alignment
Severe Acute Respiratory Syndrome
Viral Envelope Proteins / immunology
Chemical
Reg. No./Substance:
0/Antibodies, Monoclonal; 0/Antibodies, Viral; 0/Hemagglutinins, Viral; 0/Immunoglobulins; 0/Membrane Glycoproteins; 0/Viral Envelope Proteins; 107476-75-5/spike glycoprotein, coronavirus

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