Science (American Association for the Advancement of Science), 2013-05, Vol.340 (6136), p.1113-1117
2013
Volltextzugriff (PDF)
Details
- Autor(en) / Beteiligte
- Titel
- Structure of RSV Fusion Glycoprotein Trimer Bound to a Prefusion-Specific Neutralizing Antibody
- Ist Teil von
- Science (American Association for the Advancement of Science), 2013-05, Vol.340 (6136), p.1113-1117
- Ort / Verlag
- United States: American Association for the Advancement of Science
- Erscheinungsjahr
- 2013
- Quelle
- American Association for the Advancement of Science
- Beschreibungen/Notizen
- 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0036-8075eISSN: 1095-9203DOI: 10.1126/science.1234914Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4459498
- Format
- –
- Schlagworte
- Amino Acid Sequence, Amino acids, Animals, Antibodies, Antibodies, Monoclonal, Humanized - immunology, Antibodies, Neutralizing - chemistry, Antibodies, Neutralizing - immunology, Children, Crystal structure, Crystallography, X-Ray, Diseases, Epitopes, Female, Fusion, Glycoproteins, Glycoproteins - chemistry, Glycoproteins - immunology, HEK293 Cells, Human immunodeficiency virus, Human respiratory syncytial virus, Humans, Infants, Mice, Mice, Inbred BALB C, Molecular Sequence Data, Monoclonal antibodies, Mycobacterium, Neutralization Tests, Neutralizing, Palivizumab, Protein Conformation, Protein Multimerization, Protein subunits, Proteins, Respiratory syncytial virus, Respiratory Syncytial Virus Vaccines - chemistry, Respiratory Syncytial Virus Vaccines - immunology, Respiratory Syncytial Viruses - immunology, Respiratory Syncytial Viruses - physiology, Respiratory system, Risk, Trimers, Vaccination, Vaccines, Viral Fusion Proteins - chemistry, Viral Fusion Proteins - immunology, Virus Internalization, Young Children