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Cross-neutralization of human and palm civet severe acute respiratory syndrome coronaviruses by antibodies targeting the receptor-binding domain of spike protein.
J Immunol. 2006 May 15; 176(10):6085-92.JI

Abstract

The spike (S) protein of severe acute respiratory syndrome coronavirus (SARS-CoV) is considered as a protective Ag for vaccine design. We previously demonstrated that the receptor-binding domain (RBD) of S protein contains multiple conformational epitopes (Conf I-VI) that confer the major target of neutralizing Abs. Here we show that the recombinant RBDs derived from the S protein sequences of Tor2, GD03, and SZ3, the representative strains of human 2002-2003 and 2003-2004 SARS-CoV and palm civet SARS-CoV, respectively, induce in the immunized mice and rabbits high titers of cross-neutralizing Abs against pseudoviruses expressing S proteins of Tor2, GD03, and SZ3. We also demonstrate that the Tor2-RBD induced-Conf I-VI mAbs can potently neutralize both human SARS-CoV strains, Tor2 and GD03. However, only the Conf IV-VI, but not Conf I-III mAbs, neutralize civet SARS-CoV strain SZ3. All these mAbs reacted significantly with each of the three RBD variants (Tor2-RBD, GD03-RBD, and SZ3-RBD) that differ at several amino acids. Regardless, the Conf I-IV and VI epitopes were completely disrupted by single-point mutation of the conserved residues in the RBD (e.g., D429A, R441A, or D454A) and the Conf III epitope was significantly affected by E452A or D463A substitution. Interestingly, the Conf V epitope, which may overlap the receptor-binding motif and induce most potent neutralizing Abs, was conserved in these mutants. These data suggest that the major neutralizing epitopes of SARS-CoV have been apparently maintained during cross-species transmission, and that RBD-based vaccines may induce broad protection against both human and animal SARS-CoV variants.

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 available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

16670317

Citation

He, Yuxian, et al. "Cross-neutralization of Human and Palm Civet Severe Acute Respiratory Syndrome Coronaviruses By Antibodies Targeting the Receptor-binding Domain of Spike Protein." Journal of Immunology (Baltimore, Md. : 1950), vol. 176, no. 10, 2006, pp. 6085-92.
He Y, Li J, Li W, et al. Cross-neutralization of human and palm civet severe acute respiratory syndrome coronaviruses by antibodies targeting the receptor-binding domain of spike protein. J Immunol. 2006;176(10):6085-92.
He, Y., Li, J., Li, W., Lustigman, S., Farzan, M., & Jiang, S. (2006). Cross-neutralization of human and palm civet severe acute respiratory syndrome coronaviruses by antibodies targeting the receptor-binding domain of spike protein. Journal of Immunology (Baltimore, Md. : 1950), 176(10), 6085-92.
He Y, et al. Cross-neutralization of Human and Palm Civet Severe Acute Respiratory Syndrome Coronaviruses By Antibodies Targeting the Receptor-binding Domain of Spike Protein. J Immunol. 2006 May 15;176(10):6085-92. PubMed PMID: 16670317.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cross-neutralization of human and palm civet severe acute respiratory syndrome coronaviruses by antibodies targeting the receptor-binding domain of spike protein. AU - He,Yuxian, AU - Li,Jingjing, AU - Li,Wenhui, AU - Lustigman,Sara, AU - Farzan,Michael, AU - Jiang,Shibo, PY - 2006/5/4/pubmed PY - 2006/6/23/medline PY - 2006/5/4/entrez SP - 6085 EP - 92 JF - Journal of immunology (Baltimore, Md. : 1950) JO - J Immunol VL - 176 IS - 10 N2 - The spike (S) protein of severe acute respiratory syndrome coronavirus (SARS-CoV) is considered as a protective Ag for vaccine design. We previously demonstrated that the receptor-binding domain (RBD) of S protein contains multiple conformational epitopes (Conf I-VI) that confer the major target of neutralizing Abs. Here we show that the recombinant RBDs derived from the S protein sequences of Tor2, GD03, and SZ3, the representative strains of human 2002-2003 and 2003-2004 SARS-CoV and palm civet SARS-CoV, respectively, induce in the immunized mice and rabbits high titers of cross-neutralizing Abs against pseudoviruses expressing S proteins of Tor2, GD03, and SZ3. We also demonstrate that the Tor2-RBD induced-Conf I-VI mAbs can potently neutralize both human SARS-CoV strains, Tor2 and GD03. However, only the Conf IV-VI, but not Conf I-III mAbs, neutralize civet SARS-CoV strain SZ3. All these mAbs reacted significantly with each of the three RBD variants (Tor2-RBD, GD03-RBD, and SZ3-RBD) that differ at several amino acids. Regardless, the Conf I-IV and VI epitopes were completely disrupted by single-point mutation of the conserved residues in the RBD (e.g., D429A, R441A, or D454A) and the Conf III epitope was significantly affected by E452A or D463A substitution. Interestingly, the Conf V epitope, which may overlap the receptor-binding motif and induce most potent neutralizing Abs, was conserved in these mutants. These data suggest that the major neutralizing epitopes of SARS-CoV have been apparently maintained during cross-species transmission, and that RBD-based vaccines may induce broad protection against both human and animal SARS-CoV variants. SN - 0022-1767 UR - https://www.unboundmedicine.com/medline/citation/16670317/Cross_neutralization_of_human_and_palm_civet_severe_acute_respiratory_syndrome_coronaviruses_by_antibodies_targeting_the_receptor_binding_domain_of_spike_protein_ L2 - http://www.jimmunol.org/cgi/pmidlookup?view=long&pmid=16670317 DB - PRIME DP - Unbound Medicine ER -