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


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


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:24179220
Additional Information

Structure view and single mutant data analysis

Study data

No weblogo for data of varying length.
Colors: D E R H K S T N Q A V I L M F Y W C G P

Data Distribution

Studies with similar sequences (approximate matches)

Correlation with other assays (exact sequence matches)

Relevant UniProtKB Entries

Percent Identity Matching Chains Protein Accession Entry Name
100.0 RSV fusion (F) glycoprotein P03420 FUS_HRSVA
97.6 RSV fusion (F) glycoprotein P12568 FUS_HRSVL
97.2 RSV fusion (F) glycoprotein P11209 FUS_HRSVR