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Receptor-binding domain of severe acute respiratory syndrome coronavirus spike protein contains multiple conformation-dependent epitopes that induce highly potent neutralizing antibodies.
J Immunol. 2005 Apr 15; 174(8):4908-15.JI

Abstract

The spike (S) protein of severe acute respiratory syndrome associated coronavirus (SARS-CoV) is a major antigenic determinant capable of inducing protective immunity. Recently, a small fragment on the SARS-CoV S protein (residues 318-510) was characterized as a minimal receptor-binding domain (RBD), which mediates virus binding to angiotensin-converting enzyme 2, the functional receptor on susceptible cells. In this study, we demonstrated that a fusion protein containing RBD linked to human IgG1 Fc fragment (designated RBD-Fc) induced high titer of RBD-specific Abs in the immunized mice. The mouse antisera effectively neutralized infection by both SARS-CoV and SARS pseudovirus with mean 50% neutralization titers of 1/15,360 and 1/24,737, respectively. The neutralization determinants on the RBD of S protein were characterized by a panel of 27 mAbs isolated from the immunized mice. Six groups of conformation-dependent epitopes, designated as Conf I-VI, and two adjacent linear epitopes were identified by ELISA and binding competition assays. The Conf IV and Conf V mAbs significantly blocked RBD-Fc binding to angiotensin-converting enzyme 2, suggesting that their epitopes overlap with the receptor-binding sites in the S protein. Most of the mAbs (23 of 25) that recognized the conformational epitopes possessed potent neutralizing activities against SARS pseudovirus with 50% neutralizing dose ranging from 0.005 to 6.569 microg/ml. Therefore, the RBD of SARS S protein contains multiple conformational epitopes capable of inducing potent neutralizing Ab responses, and is an important target site for developing vaccines and immunotherapeutics.

Authors+Show Affiliations

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

Pub Type(s)

Journal Article

Language

eng

PubMed ID

15814718

Citation

He, Yuxian, et al. "Receptor-binding Domain of Severe Acute Respiratory Syndrome Coronavirus Spike Protein Contains Multiple Conformation-dependent Epitopes That Induce Highly Potent Neutralizing Antibodies." Journal of Immunology (Baltimore, Md. : 1950), vol. 174, no. 8, 2005, pp. 4908-15.
He Y, Lu H, Siddiqui P, et al. Receptor-binding domain of severe acute respiratory syndrome coronavirus spike protein contains multiple conformation-dependent epitopes that induce highly potent neutralizing antibodies. J Immunol. 2005;174(8):4908-15.
He, Y., Lu, H., Siddiqui, P., Zhou, Y., & Jiang, S. (2005). Receptor-binding domain of severe acute respiratory syndrome coronavirus spike protein contains multiple conformation-dependent epitopes that induce highly potent neutralizing antibodies. Journal of Immunology (Baltimore, Md. : 1950), 174(8), 4908-15.
He Y, et al. Receptor-binding Domain of Severe Acute Respiratory Syndrome Coronavirus Spike Protein Contains Multiple Conformation-dependent Epitopes That Induce Highly Potent Neutralizing Antibodies. J Immunol. 2005 Apr 15;174(8):4908-15. PubMed PMID: 15814718.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Receptor-binding domain of severe acute respiratory syndrome coronavirus spike protein contains multiple conformation-dependent epitopes that induce highly potent neutralizing antibodies. AU - He,Yuxian, AU - Lu,Hong, AU - Siddiqui,Pamela, AU - Zhou,Yusen, AU - Jiang,Shibo, PY - 2005/4/9/pubmed PY - 2005/5/18/medline PY - 2005/4/9/entrez SP - 4908 EP - 15 JF - Journal of immunology (Baltimore, Md. : 1950) JO - J Immunol VL - 174 IS - 8 N2 - The spike (S) protein of severe acute respiratory syndrome associated coronavirus (SARS-CoV) is a major antigenic determinant capable of inducing protective immunity. Recently, a small fragment on the SARS-CoV S protein (residues 318-510) was characterized as a minimal receptor-binding domain (RBD), which mediates virus binding to angiotensin-converting enzyme 2, the functional receptor on susceptible cells. In this study, we demonstrated that a fusion protein containing RBD linked to human IgG1 Fc fragment (designated RBD-Fc) induced high titer of RBD-specific Abs in the immunized mice. The mouse antisera effectively neutralized infection by both SARS-CoV and SARS pseudovirus with mean 50% neutralization titers of 1/15,360 and 1/24,737, respectively. The neutralization determinants on the RBD of S protein were characterized by a panel of 27 mAbs isolated from the immunized mice. Six groups of conformation-dependent epitopes, designated as Conf I-VI, and two adjacent linear epitopes were identified by ELISA and binding competition assays. The Conf IV and Conf V mAbs significantly blocked RBD-Fc binding to angiotensin-converting enzyme 2, suggesting that their epitopes overlap with the receptor-binding sites in the S protein. Most of the mAbs (23 of 25) that recognized the conformational epitopes possessed potent neutralizing activities against SARS pseudovirus with 50% neutralizing dose ranging from 0.005 to 6.569 microg/ml. Therefore, the RBD of SARS S protein contains multiple conformational epitopes capable of inducing potent neutralizing Ab responses, and is an important target site for developing vaccines and immunotherapeutics. SN - 0022-1767 UR - https://www.unboundmedicine.com/medline/citation/15814718/Receptor_binding_domain_of_severe_acute_respiratory_syndrome_coronavirus_spike_protein_contains_multiple_conformation_dependent_epitopes_that_induce_highly_potent_neutralizing_antibodies_ L2 - http://www.jimmunol.org/cgi/pmidlookup?view=long&pmid=15814718 DB - PRIME DP - Unbound Medicine ER -