Download MendeleyStructure-based design of a fusion glycoprotein vaccine for respiratory syncytial virus.
McLellan, J.S., Chen, M., Joyce, M.G., Sastry, M., Stewart-Jones, G.B., Yang, Y., Zhang, B., Chen, L., Srivatsan, S., Zheng, A., Zhou, T., Graepel, K.W., Kumar, A., Moin, S., Boyington, J.C., Chuang, G.Y., Soto, C., Baxa, U., Bakker, A.Q., Spits, H., Beaumont, T., Zheng, Z., Xia, N., Ko, S.Y., Todd, J.P., Rao, S., Graham, B.S., Kwong, P.D.(2013) Science 342: 592-598
- PubMed: 24179220
- DOI: https://doi.org/10.1126/science.1243283
- Primary Citation of Related Structures:
4MMQ, 4MMR, 4MMS, 4MMT, 4MMU, 4MMV - PubMed 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.
Organizational Affiliation:
Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
