Proof of principle for epitope-focused vaccine design.

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, Johnson PR, Schief WR
Nature. 2014 507 (7491): 201-6

PMID: 24499818 · PMCID: PMC4260937 · DOI:10.1038/nature12966

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.

MeSH Terms (20)

Amino 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 Viruses Respiratory Syncytial Virus Vaccines

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