Proof of principle for epitope-focused vaccine design.

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TitleProof of principle for epitope-focused vaccine design.
Publication TypeJournal Article
Year of Publication2014
AuthorsCorreia, 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, Johnson, PR, Schief, WR
JournalNature
Volume507
Issue7491
Pagination201-6
Date Published2014 Mar 13
ISSN1476-4687
KeywordsAmino Acid Motifs, Animals, Antibodies, Monoclonal, Antibodies, Neutralizing, Antibodies, Viral, Antigens, Viral, Crystallography, X-Ray, Drug Design, Enzyme-Linked Immunosorbent Assay, Epitopes, Macaca mulatta, Male, Mice, Mice, Inbred BALB C, Models, Molecular, Neutralization Tests, Protein Conformation, Protein Stability, Respiratory Syncytial Virus Vaccines, Respiratory Syncytial Viruses
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.

DOI10.1038/nature12966
Alternate JournalNature
PubMed ID24499818
Grant List1R01AI102766-01A1 / AI / NIAID NIH HHS / United States
1UM1AI100663 / AI / NIAID NIH HHS / United States
2T32GM007270 / GM / NIGMS NIH HHS / United States
5R21AI088554 / AI / NIAID NIH HHS / United States
P01 AI094419 / AI / NIAID NIH HHS / United States
P01AI094419 / AI / NIAID NIH HHS / United States
P30 AI036214 / AI / NIAID NIH HHS / United States
P30AI36214 / AI / NIAID NIH HHS / United States
R21 AI088554 / AI / NIAID NIH HHS / United States
T32 CA080416 / CA / NCI NIH HHS / United States
T32 GM007270 / GM / NIGMS NIH HHS / United States
T32CA080416 / CA / NCI NIH HHS / United States
U54 AI 005714 / AI / NIAID NIH HHS / United States
U54 AI057141 / AI / NIAID NIH HHS / United States
UM1 AI100663 / AI / NIAID NIH HHS / United States