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Open AccessJournal ArticleDOI

Structure-Based Design of a Fusion Glycoprotein Vaccine for Respiratory Syncytial Virus

Jason S. McLellan, +27 more
- 01 Nov 2013 - 
- Vol. 342, Iss: 6158, pp 592-598
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TLDR
A viral antigen is sought that provides greater protection than currently available vaccines and focused on antigenic site Ø, a metastable site specific to the prefusion state of the RSV fusion (F) glycoprotein, as this site is targeted by extremely potent RSV-neutralizing antibodies.
Abstract: 
Respiratory syncytial virus (RSV) is the leading cause of hospitalization for children under 5 years of age. We sought to engineer a viral antigen that provides greater protection than currently available vaccines and focused on antigenic site O, a metastable site specific to the prefusion state of the RSV fusion (F) glycoprotein, as this site is targeted by extremely potent RSV-neutralizing antibodies. Structure-based design yielded stabilized versions of RSV F that maintained antigenic site O when exposed to extremes of pH, osmolality, and temperature. Six RSV F crystal structures provided atomic-level data on how introduced cysteine residues and filled hydrophobic cavities improved stability. Immunization with site O–stabilized variants of RSV F in mice and macaques elicited levels of RSV-specific neutralizing activity many times the protective threshold.

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Book ChapterDOI

122 – Host Defense Mechanisms Against Viruses

James E. Crowe
References
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