title: Development and characterization of a severe acute respiratory syndrome-associated coronavirus-neutralizing human monoclonal antibody that provides effective immunoprophylaxis in mice.
abstract: BACKGROUND
  Severe acute respiratory syndrome (SARS) remains a significant public health concern after the epidemic in 2003. Human monoclonal antibodies (MAbs) that neutralize SARS-associated coronavirus (SARS-CoV) could provide protection for exposed individuals.
  
  
  METHODS
  Transgenic mice with human immunoglobulin genes were immunized with the recombinant major surface (S) glycoprotein ectodomain of SARS-CoV. Epitopes of 2 neutralizing MAbs derived from these mice were mapped and evaluated in a murine model of SARS-CoV infection.
  
  
  RESULTS
  Both MAbs bound to S glycoprotein expressed on transfected cells but differed in their ability to block binding of S glycoprotein to Vero E6 cells. Immunoprecipitation analysis revealed 2 antibody-binding epitopes: one MAb (201) bound within the receptor-binding domain at aa 490-510, and the other MAb (68) bound externally to the domain at aa 130-150. Mice that received 40 mg/kg of either MAb prior to challenge with SARS-CoV were completely protected from virus replication in the lungs, and doses as low as 1.6 mg/kg offered significant protection.
  
  
  CONCLUSIONS
  Two neutralizing epitopes were defined for MAbs to SARS-CoV S glycoprotein. Antibodies to both epitopes protected mice against SARS-CoV challenge. Clinical trials are planned to test MAb 201, a fully human MAb specific for the epitope within the receptor-binding region.
authors.affiliation: Department of Pediatrics, Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 02130, USA.
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Greenough
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Babcock
authors.forename: Anjeanette
authors.initials: A
authors.lastname: Roberts
authors.forename: Hector J
authors.initials: HJ
authors.lastname: Hernandez
authors.forename: William D
authors.initials: WD
authors.lastname: Thomas
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Coccia
authors.forename: Robert F
authors.initials: RF
authors.lastname: Graziano
authors.forename: Mohan
authors.initials: M
authors.lastname: Srinivasan
authors.forename: Israel
authors.initials: I
authors.lastname: Lowy
authors.forename: Robert W
authors.initials: RW
authors.lastname: Finberg
authors.forename: Kanta
authors.initials: K
authors.lastname: Subbarao
authors.forename: Leatrice
authors.initials: L
authors.lastname: Vogel
authors.forename: Mohan
authors.initials: M
authors.lastname: Somasundaran
authors.forename: Katherine
authors.initials: K
authors.lastname: Luzuriaga
authors.forename: John L
authors.initials: JL
authors.lastname: Sullivan
authors.forename: Donna M
authors.initials: DM
authors.lastname: Ambrosino
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000914:Antibodies, Viral / Q000627:therapeutic use*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D018604:Epitope Mapping; D000939:Epitopes / Q000276:immunology; D005260:Female; D007116:Immunization, Passive; D008168:Lung / Q000821:virology; D008562:Membrane Glycoproteins / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D009500:Neutralization Tests; D011485:Protein Binding; D045473:Severe acute respiratory syndrome-related coronavirus / Q000276:immunology*; D045169:Severe Acute Respiratory Syndrome / Q000517:prevention & control*; D064370:Spike Glycoprotein, Coronavirus; D014759:Viral Envelope Proteins / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D000939:Epitopes; D008562:Membrane Glycoproteins; D064370:Spike Glycoprotein, Coronavirus; D014759:Viral Envelope Proteins