Development and characterization of a severe acute respiratory syndrome-associated coronavirus-neutralizing human monoclonal antibody that provides effective immunoprophylaxis in mice
Department of Pediatrics; Massachusetts Biologic Laboratories; Program in Molecular Medicine
Animals; Antibodies, Monoclonal; Antibodies, Viral; Cells, Cultured; Disease Models, Animal; Epitope Mapping; Epitopes; Female; *Immunization, Passive; Lung; Membrane Glycoproteins; Mice; Mice, Inbred BALB C; Mice, Transgenic; Neutralization Tests; Protein Binding; SARS Virus; Severe Acute Respiratory Syndrome; Viral Envelope Proteins
Immunology and Infectious Disease | Pediatrics
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.
DOI of Published Version
J Infect Dis. 2005 Feb 15;191(4):507-14. Epub 2005 Jan 14. Link to article on publisher's site
The Journal of infectious diseases
Greenough TC, Babcock GJ, Roberts A, Hernandez HJ, Thomas WD, Coccia JA, Graziano RF, Srinivasan M, Lowy I, Finberg RW, Subbarao K, Vogel L, Somasundaran M, Luzuriaga K, Sullivan JL, Ambrosino DM. (2005). Development and characterization of a severe acute respiratory syndrome-associated coronavirus-neutralizing human monoclonal antibody that provides effective immunoprophylaxis in mice. Immunology/Infectious Disease. https://doi.org/10.1086/427242. Retrieved from https://escholarship.umassmed.edu/peds_immunology/47