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Identification and characterization of novel neutralizing epitopes in the receptor-binding domain of SARS-CoV spike protein: revealing the critical antigenic determinants in inactivated SARS-CoV vaccine.
Vaccine. 2006 Jun 29; 24(26):5498-508.V

Abstract

The spike (S) protein of severe acute respiratory syndrome coronavirus (SARS-CoV) is considered as a major antigen for vaccine design. We previously demonstrated that the receptor-binding domain (RBD: residues 318-510) of S protein contains multiple conformation-dependent neutralizing epitopes (Conf I to VI) and serves as a major target of SARS-CoV neutralization. Here, we further characterized the antigenic structure in the RBD by a panel of novel mAbs isolated from the mice immunized with an inactivated SARS-CoV vaccine. Ten of the RBD-specific mAbs were mapped to four distinct groups of conformational epitopes (designated Group A to D), and all of which had potent neutralizing activity against S protein-pseudotyped SARS viruses. Group A, B, C mAbs target the epitopes that may overlap with the previously characterized Conf I, III, and VI respectively, but they display different capacity to block the receptor binding. Group D mAb (S25) was directed against a unique epitope by its competitive binding. Two anti-RBD mAbs recognizing the linear epitopes (Group E) were mapped to the RBD residues 335-352 and 442-458, respectively, and none of them inhibited the receptor binding and virus entry. Surprisingly, most neutralizing epitopes (Groups A to C) could be completely disrupted by single amino acid substitutions (e.g., D429A, R441A or D454A) or by deletions of several amino acids at the N-terminal or C-terminal region of the RBD; however, the Group D epitope was not sensitive to the mutations, highlighting its importance for vaccine development. These data provide important information for understanding the antigenicity and immunogenicity of SARS-CoV, and this panel of novel mAbs can be used as tools for studying the structure of S protein and for guiding SARS vaccine design.

Authors+Show Affiliations

Lindsley F. Kimball Research Institute, New York Blood Center, 310 East 67th Street, New York, NY 10021, USA. yhe@nybloodcenter.orgNo 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

16725238

Citation

He, Yuxian, et al. "Identification and Characterization of Novel Neutralizing Epitopes in the Receptor-binding Domain of SARS-CoV Spike Protein: Revealing the Critical Antigenic Determinants in Inactivated SARS-CoV Vaccine." Vaccine, vol. 24, no. 26, 2006, pp. 5498-508.
He Y, Li J, Du L, et al. Identification and characterization of novel neutralizing epitopes in the receptor-binding domain of SARS-CoV spike protein: revealing the critical antigenic determinants in inactivated SARS-CoV vaccine. Vaccine. 2006;24(26):5498-508.
He, Y., Li, J., Du, L., Yan, X., Hu, G., Zhou, Y., & Jiang, S. (2006). Identification and characterization of novel neutralizing epitopes in the receptor-binding domain of SARS-CoV spike protein: revealing the critical antigenic determinants in inactivated SARS-CoV vaccine. Vaccine, 24(26), 5498-508.
He Y, et al. Identification and Characterization of Novel Neutralizing Epitopes in the Receptor-binding Domain of SARS-CoV Spike Protein: Revealing the Critical Antigenic Determinants in Inactivated SARS-CoV Vaccine. Vaccine. 2006 Jun 29;24(26):5498-508. PubMed PMID: 16725238.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Identification and characterization of novel neutralizing epitopes in the receptor-binding domain of SARS-CoV spike protein: revealing the critical antigenic determinants in inactivated SARS-CoV vaccine. AU - He,Yuxian, AU - Li,Jingjing, AU - Du,Lanying, AU - Yan,Xuxia, AU - Hu,Guangan, AU - Zhou,Yusen, AU - Jiang,Shibo, Y1 - 2006/05/11/ PY - 2006/03/07/received PY - 2006/04/09/revised PY - 2006/04/17/accepted PY - 2006/5/27/pubmed PY - 2006/10/27/medline PY - 2006/5/27/entrez SP - 5498 EP - 508 JF - Vaccine JO - Vaccine VL - 24 IS - 26 N2 - The spike (S) protein of severe acute respiratory syndrome coronavirus (SARS-CoV) is considered as a major antigen for vaccine design. We previously demonstrated that the receptor-binding domain (RBD: residues 318-510) of S protein contains multiple conformation-dependent neutralizing epitopes (Conf I to VI) and serves as a major target of SARS-CoV neutralization. Here, we further characterized the antigenic structure in the RBD by a panel of novel mAbs isolated from the mice immunized with an inactivated SARS-CoV vaccine. Ten of the RBD-specific mAbs were mapped to four distinct groups of conformational epitopes (designated Group A to D), and all of which had potent neutralizing activity against S protein-pseudotyped SARS viruses. Group A, B, C mAbs target the epitopes that may overlap with the previously characterized Conf I, III, and VI respectively, but they display different capacity to block the receptor binding. Group D mAb (S25) was directed against a unique epitope by its competitive binding. Two anti-RBD mAbs recognizing the linear epitopes (Group E) were mapped to the RBD residues 335-352 and 442-458, respectively, and none of them inhibited the receptor binding and virus entry. Surprisingly, most neutralizing epitopes (Groups A to C) could be completely disrupted by single amino acid substitutions (e.g., D429A, R441A or D454A) or by deletions of several amino acids at the N-terminal or C-terminal region of the RBD; however, the Group D epitope was not sensitive to the mutations, highlighting its importance for vaccine development. These data provide important information for understanding the antigenicity and immunogenicity of SARS-CoV, and this panel of novel mAbs can be used as tools for studying the structure of S protein and for guiding SARS vaccine design. SN - 0264-410X UR - https://www.unboundmedicine.com/medline/citation/16725238/Identification_and_characterization_of_novel_neutralizing_epitopes_in_the_receptor_binding_domain_of_SARS_CoV_spike_protein:_revealing_the_critical_antigenic_determinants_in_inactivated_SARS_CoV_vaccine_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0264-410X(06)00446-4 DB - PRIME DP - Unbound Medicine ER -