Epitopes described in "Structure of RSV fusion glycoprotein trimer bound to a prefusion-specific neutralizing antibody."

Article Authors:Jason S McLellan; Man Chen; Sherman Leung; Kevin W Graepel; Xiulian Du; Yongping Yang; Tongqing Zhou; Ulrich Baxa; Etsuko Yasuda; Tim Beaumont; Azad Kumar; Kayvon Modjarrad; Zizheng Zheng; Min Zhao; Ningshao Xia; Peter D Kwong; Barney S Graham
Article Title:Structure of RSV fusion glycoprotein trimer bound to a prefusion-specific neutralizing antibody.
Reference Detail
Reference ID:1026287
Abstract:The prefusion state of respiratory syncytial virus (RSV) fusion (F) glycoprotein is the target of most RSV-neutralizing activity in human sera, but its metastability has hindered characterization. To overcome this obstacle, we identified prefusion-specific antibodies that were substantially more potent than the prophylactic antibody palivizumab. The cocrystal structure for one of these antibodies, D25, in complex with the F glycoprotein revealed D25 to lock F in its prefusion state by binding to a quaternary epitope at the trimer apex. Electron microscopy showed that two other antibodies, AM22 and 5C4, also bound to the newly identified site of vulnerability, which we named antigenic site Ø. These studies should enable design of improved vaccine antigens and define new targets for passive prevention of RSV-induced disease.
Affiliations:Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. mclellanja@niaid.nih.gov
Reference Type:Literature
PubMed ID:23618766
Journal Volume:340
Article Pages:1113-7
Journal ISSN:1095-9203
Article Chemical List:Antibodies, Monoclonal, Humanized;Antibodies, Neutralizing;Glycoproteins;Respiratory Syncytial Virus Vaccines;Viral Fusion Proteins;palivizumab
Article MeSH List:Amino Acid Sequence; Animals; Antibodies, Monoclonal, Humanized(immunology); Antibodies, Neutralizing(chemistry; immunology); Crystallography, X-Ray; Female; Glycoproteins(chemistry; immunology); HEK293 Cells; Humans; Mice; Mice, Inbred BALB C; Molecular Sequence Data; Neutralization Tests; Protein Conformation; Protein Multimerization; Respiratory Syncytial Virus Vaccines(chemistry; immunology); Respiratory Syncytial Viruses(immunology; physiology); Viral Fusion Proteins(chemistry; immunology); Virus Internalization
Curation Last Updated:2014-10-03 22:55:26