4mmt
Crystal Structure of Prefusion-stabilized RSV F Variant DS-Cav1 at pH 9.5Crystal Structure of Prefusion-stabilized RSV F Variant DS-Cav1 at pH 9.5
Structural highlights
Publication Abstract from PubMedRespiratory 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. Structure-based design of a fusion glycoprotein vaccine for respiratory syncytial virus.,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 Nov 1;342(6158):592-8. doi: 10.1126/science.1243283. PMID:24179220[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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