tetano
Editor, Senior Moderator
Nature. 2014 Feb 5. doi: 10.1038/nature12966. [Epub ahead of print]
Proof of principle for epitope-focused vaccine design.
Correia BE1, Bates JT2, Loomis RJ3, Baneyx G4, Carrico C5, Jardine JG6, Rupert P5, Correnti C5, Kalyuzhniy O7, Vittal V4, Connell MJ3, Stevens E4, Schroeter A4, Chen M8, Macpherson S6, Serra AM7, Adachi Y7, Holmes MA9, Li Y10, Klevit RE4, Graham BS8, Wyatt RT10, Baker D4, Strong RK5, Crowe JE11, Johnson PR3, Schief WR6.
Author information
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.
PMID:
24499818
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/24499818
Proof of principle for epitope-focused vaccine design.
Correia BE1, Bates JT2, Loomis RJ3, Baneyx G4, Carrico C5, Jardine JG6, Rupert P5, Correnti C5, Kalyuzhniy O7, Vittal V4, Connell MJ3, Stevens E4, Schroeter A4, Chen M8, Macpherson S6, Serra AM7, Adachi Y7, Holmes MA9, Li Y10, Klevit RE4, Graham BS8, Wyatt RT10, Baker D4, Strong RK5, Crowe JE11, Johnson PR3, Schief WR6.
Author information
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.
PMID:
24499818
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/24499818