Epitopes described in "Development and characterization of a severe acute respiratory syndrome-associated coronavirus-neutralizing human monoclonal antibody that provides effective immunoprophylaxis in mice."

Reference
Article Authors:Thomas C Greenough; Gregory J Babcock; Anjeanette Roberts; Hector J Hernandez; William D Thomas Jr; Jennifer A Coccia; Robert F Graziano; Mohan Srinivasan; Israel Lowy; Robert W Finberg; Kanta Subbarao; Leatrice Vogel; Mohan Somasundaran; Katherine Luzuriaga; John L Sullivan; Donna M Ambrosino
Article Title:Development and characterization of a severe acute respiratory syndrome-associated coronavirus-neutralizing human monoclonal antibody that provides effective immunoprophylaxis in mice.
Reference Detail
Reference ID:454
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.
Date:2005
Reference Type:Literature
PubMed ID:15655773
Journal:J Infect Dis
Journal Volume:191
Article Pages:507-14
Journal ISSN:1537-6613
Article Chemical List:Antibodies, Monoclonal;Antibodies, Viral;Epitopes;Membrane Glycoproteins;Spike Glycoprotein, Coronavirus;Viral Envelope Proteins
Article MeSH List:Animals; Antibodies, Monoclonal(therapeutic use); Antibodies, Viral(therapeutic use); Cells, Cultured; Disease Models, Animal; Epitope Mapping; Epitopes(immunology); Female; Immunization, Passive; Lung(virology); Membrane Glycoproteins(immunology); Mice; Mice, Inbred BALB C; Mice, Transgenic; Neutralization Tests; Protein Binding; SARS Virus(immunology); Severe Acute Respiratory Syndrome(prevention & control); Spike Glycoprotein, Coronavirus; Viral Envelope Proteins(immunology)
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