Back to Search
Start Over
Characterization of a Prefusion-Specific Antibody That Recognizes a Quaternary, Cleavage-Dependent Epitope on the RSV Fusion Glycoprotein.
- Source :
-
PLoS pathogens [PLoS Pathog] 2015 Jul 10; Vol. 11 (7), pp. e1005035. Date of Electronic Publication: 2015 Jul 10 (Print Publication: 2015). - Publication Year :
- 2015
-
Abstract
- Prevention efforts for respiratory syncytial virus (RSV) have been advanced due to the recent isolation and characterization of antibodies that specifically recognize the prefusion conformation of the RSV fusion (F) glycoprotein. These potently neutralizing antibodies are in clinical development for passive prophylaxis and have also aided the design of vaccine antigens that display prefusion-specific epitopes. To date, prefusion-specific antibodies have been shown to target two antigenic sites on RSV F, but both of these sites are also present on monomeric forms of F. Here we present a structural and functional characterization of human antibody AM14, which potently neutralized laboratory strains and clinical isolates of RSV from both A and B subtypes. The crystal structure and location of escape mutations revealed that AM14 recognizes a quaternary epitope that spans two protomers and includes a region that undergoes extensive conformational changes in the pre- to postfusion F transition. Binding assays demonstrated that AM14 is unique in its specific recognition of trimeric furin-cleaved prefusion F, which is the mature form of F on infectious virions. These results demonstrate that the prefusion F trimer contains potent neutralizing epitopes not present on monomers and that AM14 should be particularly useful for characterizing the conformational state of RSV F-based vaccine antigens.
- Subjects :
- Antibodies, Neutralizing chemistry
Antibodies, Neutralizing immunology
Antibodies, Viral chemistry
Antibodies, Viral immunology
Antigens, Viral immunology
Cell Line
Chromatography, Gel
Crystallography, X-Ray
Enzyme-Linked Immunosorbent Assay
Epitope Mapping
Epitopes, B-Lymphocyte chemistry
Epitopes, B-Lymphocyte immunology
Flow Cytometry
Glycoproteins chemistry
Glycoproteins immunology
Glycoproteins ultrastructure
Humans
Protein Structure, Quaternary
Surface Plasmon Resonance
Antibodies, Neutralizing ultrastructure
Antibodies, Viral ultrastructure
Epitopes, B-Lymphocyte ultrastructure
Respiratory Syncytial Viruses immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1553-7374
- Volume :
- 11
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- PLoS pathogens
- Publication Type :
- Academic Journal
- Accession number :
- 26161532
- Full Text :
- https://doi.org/10.1371/journal.ppat.1005035