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Proof of principle for epitope-focused vaccine design.

Authors :
Correia BE
Bates JT
Loomis RJ
Baneyx G
Carrico C
Jardine JG
Rupert P
Correnti C
Kalyuzhniy O
Vittal V
Connell MJ
Stevens E
Schroeter A
Chen M
Macpherson S
Serra AM
Adachi Y
Holmes MA
Li Y
Klevit RE
Graham BS
Wyatt RT
Baker D
Strong RK
Crowe JE Jr
Johnson PR
Schief WR
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.

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