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 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. Structure-based design yielded stabilized versions of RSV F that maintained antigenic site Ø 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 Ø-stabilized variants of RSV F in mice and macaques elicited levels of RSV-specific neutralizing activity many times the protective threshold.
Submitter: Connie Wang
Submission Date: Nov. 30, 2016, 11:16 a.m.
|Number of data points||516|
|Proteins||RSV fusion (F) glycoprotein|
|Assays/Quantities/Protocols||Experimental Assay: Mota Binding upon expression ; Experimental Assay: D25 Binding after 1 week at 4 C ; Experimental Assay: D25 Binding upon expression ; Experimental Assay: Mota Binding after 1 week at 4 C|
|Libraries||Engineered RSV F glycoprotein|