Proof of principle for epitope-focused vaccine design

Bruno E. Correia, John T. Bates, Rebecca J. Loomis, Gretchen Baneyx, Chris Carrico, Joseph G. Jardine, Peter Rupert, Colin Correnti, Oleksandr Kalyuzhniy, Vinayak Vittal, Mary J. Connell, Eric Stevens, Alexandria Schroeter, Man Chen, Skye MacPherson, Andreia M. Serra, Yumiko Adachi, Margaret A. Holmes, Yuxing Li, Rachel E. Klevit, Barney S. Graham, Richard T. Wyatt, David Baker, Roland K. Strong, James E. Crowe, Philip R. Johnson and William R. Schief ()
Additional contact information
Bruno E. Correia: University of Washington
John T. Bates: The Vanderbilt Vaccine Center, Vanderbilt University Medical Center
Rebecca J. Loomis: The Children’s Hospital of Philadelphia Research Institute
Gretchen Baneyx: University of Washington
Chris Carrico: Fred Hutchinson Cancer Research Center
Joseph G. Jardine: University of Washington
Peter Rupert: Fred Hutchinson Cancer Research Center
Colin Correnti: Fred Hutchinson Cancer Research Center
Oleksandr Kalyuzhniy: University of Washington
Vinayak Vittal: University of Washington
Mary J. Connell: The Children’s Hospital of Philadelphia Research Institute
Eric Stevens: University of Washington
Alexandria Schroeter: University of Washington
Man Chen: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health
Skye MacPherson: University of Washington
Andreia M. Serra: University of Washington
Yumiko Adachi: University of Washington
Margaret A. Holmes: Fred Hutchinson Cancer Research Center
Yuxing Li: The Scripps Research Institute
Rachel E. Klevit: University of Washington
Barney S. Graham: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health
Richard T. Wyatt: The Scripps Research Institute
David Baker: University of Washington
Roland K. Strong: Fred Hutchinson Cancer Research Center
James E. Crowe: The Vanderbilt Vaccine Center, Vanderbilt University Medical Center
Philip R. Johnson: The Children’s Hospital of Philadelphia Research Institute
William R. Schief: University of Washington

Nature, 2014, vol. 507, issue 7491, 201-206

Abstract: 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.

Date: 2014
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DOI: 10.1038/nature12966

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