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Identification of a critical neutralization determinant of severe acute respiratory syndrome (SARS)-associated coronavirus: importance for designing SARS vaccines.
Virology. 2005 Mar 30; 334(1):74-82.V

Abstract

The spike (S) protein of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) is not only responsible for receptor binding, but also a major antigenic determinant capable of inducing protective immunity. In this study, we demonstrated that the receptor-binding domain (RBD) of S protein is an important immunogenic site in patients with SARS and rabbits immunized with inactivated SARS-CoV. Serum samples from convalescent SARS patients and immunized rabbits had potent neutralizing activities against infection by pseudovirus expressing SARS-CoV S protein. Depletion of RBD-specific antibodies from patient or rabbit immune sera by immunoadsorption significantly reduced serum-mediated neutralizing activity, while affinity-purified anti-RBD antibodies had relatively higher potency neutralizing infectivity of SARS pseudovirus, indicating that the RBD of S protein is a critical neutralization determinant of SARS-CoV during viral infection and immunization. Two monoclonal antibodies (1A5 and 2C5) targeting at the RBD of S protein were isolated from mice immunized with inactivated SARS-CoV. Both 1A5 and 2C5 possessed potent neutralizing activities, although they directed against distinct conformation-dependant epitopes as shown by ELISA and binding competition assay. We further demonstrated that 2C5, but not 1A5, was able to block binding of the RBD to angiotensin-converting enzyme 2 (ACE2), the functional receptor on targeted cells. These data provide important information for understanding the antigenicity and immunogenicity of SARS-CoV and for designing SARS vaccines.

Authors+Show Affiliations

Viral Immunology Laboratory, Lindsley F. Kimball Research Institute, New York Blood Center, 310 East 67th Street, New York, NY 10021, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

15749124

Citation

He, Yuxian, et al. "Identification of a Critical Neutralization Determinant of Severe Acute Respiratory Syndrome (SARS)-associated Coronavirus: Importance for Designing SARS Vaccines." Virology, vol. 334, no. 1, 2005, pp. 74-82.
He Y, Zhu Q, Liu S, et al. Identification of a critical neutralization determinant of severe acute respiratory syndrome (SARS)-associated coronavirus: importance for designing SARS vaccines. Virology. 2005;334(1):74-82.
He, Y., Zhu, Q., Liu, S., Zhou, Y., Yang, B., Li, J., & Jiang, S. (2005). Identification of a critical neutralization determinant of severe acute respiratory syndrome (SARS)-associated coronavirus: importance for designing SARS vaccines. Virology, 334(1), 74-82.
He Y, et al. Identification of a Critical Neutralization Determinant of Severe Acute Respiratory Syndrome (SARS)-associated Coronavirus: Importance for Designing SARS Vaccines. Virology. 2005 Mar 30;334(1):74-82. PubMed PMID: 15749124.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Identification of a critical neutralization determinant of severe acute respiratory syndrome (SARS)-associated coronavirus: importance for designing SARS vaccines. AU - He,Yuxian, AU - Zhu,Qingyu, AU - Liu,Shuwen, AU - Zhou,Yusen, AU - Yang,Baoan, AU - Li,Jiaming, AU - Jiang,Shibo, PY - 2004/12/03/received PY - 2005/01/04/revised PY - 2005/01/26/accepted PY - 2005/3/8/pubmed PY - 2005/4/29/medline PY - 2005/3/8/entrez SP - 74 EP - 82 JF - Virology JO - Virology VL - 334 IS - 1 N2 - The spike (S) protein of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) is not only responsible for receptor binding, but also a major antigenic determinant capable of inducing protective immunity. In this study, we demonstrated that the receptor-binding domain (RBD) of S protein is an important immunogenic site in patients with SARS and rabbits immunized with inactivated SARS-CoV. Serum samples from convalescent SARS patients and immunized rabbits had potent neutralizing activities against infection by pseudovirus expressing SARS-CoV S protein. Depletion of RBD-specific antibodies from patient or rabbit immune sera by immunoadsorption significantly reduced serum-mediated neutralizing activity, while affinity-purified anti-RBD antibodies had relatively higher potency neutralizing infectivity of SARS pseudovirus, indicating that the RBD of S protein is a critical neutralization determinant of SARS-CoV during viral infection and immunization. Two monoclonal antibodies (1A5 and 2C5) targeting at the RBD of S protein were isolated from mice immunized with inactivated SARS-CoV. Both 1A5 and 2C5 possessed potent neutralizing activities, although they directed against distinct conformation-dependant epitopes as shown by ELISA and binding competition assay. We further demonstrated that 2C5, but not 1A5, was able to block binding of the RBD to angiotensin-converting enzyme 2 (ACE2), the functional receptor on targeted cells. These data provide important information for understanding the antigenicity and immunogenicity of SARS-CoV and for designing SARS vaccines. SN - 0042-6822 UR - https://www.unboundmedicine.com/medline/citation/15749124/Identification_of_a_critical_neutralization_determinant_of_severe_acute_respiratory_syndrome__SARS__associated_coronavirus:_importance_for_designing_SARS_vaccines_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0042-6822(05)00067-X DB - PRIME DP - Unbound Medicine ER -