title: Generation and characterization of human monoclonal neutralizing antibodies with distinct binding and sequence features against SARS coronavirus using XenoMouse.
abstract: 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.affiliation: Department of Microbiology and Immunology (MC790) College of Medicine, University of Illinois at Chicago, Room E705. 835 S. Wolcott AveChicago, IL 60612, USA.
authors.forename: Melissa
authors.initials: M
authors.lastname: Coughlin
authors.forename: Gin
authors.initials: G
authors.lastname: Lou
authors.forename: Osvaldo
authors.initials: O
authors.lastname: Martinez
authors.forename: Stephanie K
authors.initials: SK
authors.lastname: Masterman
authors.forename: Ole A
authors.initials: OA
authors.lastname: Olsen
authors.forename: Angelica A
authors.initials: AA
authors.lastname: Moksa
authors.forename: Michael
authors.initials: M
authors.lastname: Farzan
authors.forename: John S
authors.initials: JS
authors.lastname: Babcook
authors.forename: Bellur S
authors.initials: BS
authors.lastname: Prabhakar
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D000914:Antibodies, Viral / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D000918:Antibody Specificity; D006389:Hemagglutinins, Viral / Q000276:immunology; D006801:Humans; D006825:Hybridomas; D007136:Immunoglobulins / Q000235:genetics / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D045473:Severe acute respiratory syndrome-related coronavirus / Q000276:immunology*; D016415:Sequence Alignment; D045169:Severe Acute Respiratory Syndrome; D064370:Spike Glycoprotein, Coronavirus; D014759:Viral Envelope Proteins / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D006389:Hemagglutinins, Viral; D007136:Immunoglobulins; D008562:Membrane Glycoproteins; D064370:Spike Glycoprotein, Coronavirus; D014759:Viral Envelope Proteins; C578557:spike glycoprotein, SARS-CoV; C578553:spike protein, mouse hepatitis virus