Source:http://linkedlifedata.com/resource/pubmed/id/16670317
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
10
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pubmed:dateCreated |
2006-5-3
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pubmed:abstractText |
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.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antibodies, Monoclonal,
http://linkedlifedata.com/resource/pubmed/chemical/Antibodies, Viral,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Glycoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Virus,
http://linkedlifedata.com/resource/pubmed/chemical/Viral Envelope Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/spike glycoprotein, coronavirus
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pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
0022-1767
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
176
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
6085-92
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:16670317-Animals,
pubmed-meshheading:16670317-Antibodies, Monoclonal,
pubmed-meshheading:16670317-Antibodies, Viral,
pubmed-meshheading:16670317-Binding Sites, Antibody,
pubmed-meshheading:16670317-Cross Reactions,
pubmed-meshheading:16670317-Female,
pubmed-meshheading:16670317-Humans,
pubmed-meshheading:16670317-Membrane Glycoproteins,
pubmed-meshheading:16670317-Mice,
pubmed-meshheading:16670317-Mice, Inbred BALB C,
pubmed-meshheading:16670317-Neutralization Tests,
pubmed-meshheading:16670317-Protein Structure, Tertiary,
pubmed-meshheading:16670317-Rabbits,
pubmed-meshheading:16670317-Receptors, Virus,
pubmed-meshheading:16670317-SARS Virus,
pubmed-meshheading:16670317-Viral Envelope Proteins,
pubmed-meshheading:16670317-Viverridae
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pubmed:year |
2006
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pubmed:articleTitle |
Cross-neutralization of human and palm civet severe acute respiratory syndrome coronaviruses by antibodies targeting the receptor-binding domain of spike protein.
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pubmed:affiliation |
Lindsley F. Kimball Research Institute, New York Blood Center, 310 East 67th Street, New York, NY 10021, USA. yhe@NYBloodcenter.org
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pubmed:publicationType |
Journal Article
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