Structure-Based Design of a Fusion Glycoprotein Vaccine for Respiratory Syncytial Virus
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 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.
Submission Details
ID: XKNFF3UT3
Submitter: Connie Wang
Submission Date: July 31, 2017, 11:46 a.m.
Version: 1
Publication Details
McLellan JS;Chen M;Joyce MG;Sastry M;Stewart-Jones GB;Yang Y;Zhang B;Chen L;Srivatsan S;Zheng A;Zhou T;Graepel KW;Kumar A;Moin S;Boyington JC;Chuang GY;Soto C;Baxa U;Bakker AQ;Spits H;Beaumont T;Zheng Z;Xia N;Ko SY;Todd JP;Rao S;Graham BS;Kwong PD,Science (2013) Structure-based design of a fusion glycoprotein vaccine for respiratory syncytial virus. PMID:24179220Additional Information
Study Summary
| Number of data points | 516 |
| Proteins | RSV fusion (F) glycoprotein |
| Unique complexes | 124 |
| 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 |
Structure view and single mutant data analysis
Study data
| Colors: | D | E | R | H | K | S | T | N | Q | A | V | I | L | M | F | Y | W | C | G | P |
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Data Distribution
Studies with similar sequences (approximate matches)