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Development and characterization of a severe acute respiratory syndrome-associated coronavirus-neutralizing human monoclonal antibody that provides effective immunoprophylaxis in mice.
J Infect Dis. 2005 Feb 15; 191(4):507-14.JI

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+Show Affiliations

Department of Pediatrics, Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 02130, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

15655773

Citation

Greenough, Thomas C., et al. "Development and Characterization of a Severe Acute Respiratory Syndrome-associated Coronavirus-neutralizing Human Monoclonal Antibody That Provides Effective Immunoprophylaxis in Mice." The Journal of Infectious Diseases, vol. 191, no. 4, 2005, pp. 507-14.
Greenough TC, Babcock GJ, Roberts A, et al. Development and characterization of a severe acute respiratory syndrome-associated coronavirus-neutralizing human monoclonal antibody that provides effective immunoprophylaxis in mice. J Infect Dis. 2005;191(4):507-14.
Greenough, T. C., Babcock, G. J., Roberts, A., Hernandez, H. J., Thomas, W. D., Coccia, J. A., Graziano, R. F., Srinivasan, M., Lowy, I., Finberg, R. W., Subbarao, K., Vogel, L., Somasundaran, M., Luzuriaga, K., Sullivan, J. L., & Ambrosino, D. M. (2005). Development and characterization of a severe acute respiratory syndrome-associated coronavirus-neutralizing human monoclonal antibody that provides effective immunoprophylaxis in mice. The Journal of Infectious Diseases, 191(4), 507-14.
Greenough TC, et al. Development and Characterization of a Severe Acute Respiratory Syndrome-associated Coronavirus-neutralizing Human Monoclonal Antibody That Provides Effective Immunoprophylaxis in Mice. J Infect Dis. 2005 Feb 15;191(4):507-14. PubMed PMID: 15655773.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Development and characterization of a severe acute respiratory syndrome-associated coronavirus-neutralizing human monoclonal antibody that provides effective immunoprophylaxis in mice. AU - Greenough,Thomas C, AU - Babcock,Gregory J, AU - Roberts,Anjeanette, AU - Hernandez,Hector J, AU - Thomas,William D,Jr AU - Coccia,Jennifer A, AU - Graziano,Robert F, AU - Srinivasan,Mohan, AU - Lowy,Israel, AU - Finberg,Robert W, AU - Subbarao,Kanta, AU - Vogel,Leatrice, AU - Somasundaran,Mohan, AU - Luzuriaga,Katherine, AU - Sullivan,John L, AU - Ambrosino,Donna M, Y1 - 2005/01/14/ PY - 2004/06/24/received PY - 2004/08/23/accepted PY - 2005/1/19/pubmed PY - 2005/3/9/medline PY - 2005/1/19/entrez SP - 507 EP - 14 JF - The Journal of infectious diseases JO - J Infect Dis VL - 191 IS - 4 N2 - 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. SN - 0022-1899 UR - https://www.unboundmedicine.com/medline/citation/15655773/Development_and_characterization_of_a_severe_acute_respiratory_syndrome_associated_coronavirus_neutralizing_human_monoclonal_antibody_that_provides_effective_immunoprophylaxis_in_mice_ L2 - https://academic.oup.com/jid/article-lookup/doi/10.1086/427242 DB - PRIME DP - Unbound Medicine ER -