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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Dey, Antu K. Dormitzer, Philip R. Shaw, Christine A. Settembre, Ethan C. Carfi, Andrea Rappuoli, Rino Swanson, Kurt A. Mandl, Christian W. |
| Description | Author Affiliation: Swanson KA ( Novartis Vaccines and Diagnostics, Cambridge, MA 02139, USA.); |
| Abstract | Respiratory syncytial virus (RSV), the main cause of infant bronchiolitis, remains a major unmet vaccine need despite more than 40 years of vaccine research. Vaccine candidates based on a chief RSV neutralization antigen, the fusion (F) glycoprotein, have foundered due to problems with stability, purity, reproducibility, and potency. Crystal structures of related parainfluenza F glycoproteins have revealed a large conformational change between the prefusion and postfusion states, suggesting that postfusion F antigens might not efficiently elicit neutralizing antibodies. We have generated a homogeneous, stable, and reproducible postfusion RSV F immunogen that elicits high titers of neutralizing antibodies in immunized animals. The 3.2-Å X-ray crystal structure of this substantially complete RSV F reveals important differences from homology-based structural models. Specifically, the RSV F crystal structure demonstrates the exposure of key neutralizing antibody binding sites on the surface of the postfusion RSV F trimer. This unanticipated structural feature explains the engineered RSV F antigen's efficiency as an immunogen. This work illustrates how structural-based antigen design can guide the rational optimization of candidate vaccine antigens. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 23 |
| Volume Number | 108 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2011-06-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Antibodies, Viral Immunology Respiratory Syncytial Virus Infections Respiratory Syncytial Viruses Viral Fusion Proteins Amino Acid Sequence Animals Antibodies, Monoclonal Metabolism Antibodies, Monoclonal, Humanized Antibodies, Neutralizing Binding Sites, Antibody Circular Dichroism Crystallography, X-Ray Immunization Infant Mice Mice, Inbred BALB C Microscopy, Electron Models, Molecular Molecular Sequence Data Palivizumab Protein Multimerization Protein Structure, Secondary Protein Structure, Tertiary Virology Genetics Sequence Homology, Amino Acid Sigmodontinae Chemistry Ultrastructure Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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