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Proof of principle for epitope-focused vaccine design.
- Source :
-
Nature [Nature] 2014 Mar 13; Vol. 507 (7491), pp. 201-6. Date of Electronic Publication: 2014 Feb 05. - Publication Year :
- 2014
-
Abstract
- Vaccines prevent infectious disease largely by inducing protective neutralizing antibodies against vulnerable epitopes. Several major pathogens have resisted traditional vaccine development, although vulnerable epitopes targeted by neutralizing antibodies have been identified for several such cases. Hence, new vaccine design methods to induce epitope-specific neutralizing antibodies are needed. Here we show, with a neutralization epitope from respiratory syncytial virus, that computational protein design can generate small, thermally and conformationally stable protein scaffolds that accurately mimic the viral epitope structure and induce potent neutralizing antibodies. These scaffolds represent promising leads for the research and development of a human respiratory syncytial virus vaccine needed to protect infants, young children and the elderly. More generally, the results provide proof of principle for epitope-focused and scaffold-based vaccine design, and encourage the evaluation and further development of these strategies for a variety of other vaccine targets, including antigenically highly variable pathogens such as human immunodeficiency virus and influenza.
- Subjects :
- Amino Acid Motifs
Animals
Antibodies, Monoclonal analysis
Antibodies, Monoclonal immunology
Antibodies, Neutralizing analysis
Antibodies, Neutralizing immunology
Antibodies, Viral analysis
Antibodies, Viral immunology
Antigens, Viral chemistry
Antigens, Viral immunology
Crystallography, X-Ray
Enzyme-Linked Immunosorbent Assay
Macaca mulatta immunology
Male
Mice
Mice, Inbred BALB C
Models, Molecular
Neutralization Tests
Protein Conformation
Respiratory Syncytial Viruses chemistry
Respiratory Syncytial Viruses immunology
Drug Design
Epitopes chemistry
Epitopes immunology
Protein Stability
Respiratory Syncytial Virus Vaccines chemistry
Respiratory Syncytial Virus Vaccines immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1476-4687
- Volume :
- 507
- Issue :
- 7491
- Database :
- MEDLINE
- Journal :
- Nature
- Publication Type :
- Academic Journal
- Accession number :
- 24499818
- Full Text :
- https://doi.org/10.1038/nature12966