Structure-based design of a fusion glycoprotein vaccine for respiratory syncytial virus

Jason S. McLellan, Man Chen, M. Gordon Joyce, Mallika Sastry, Guillaume B.E. Stewart-Jones, Yongping Yang, Baoshan Zhang, Lei Chen, Sanjay Srivatsan, Anqi Zheng, Tongqing Zhou, Kevin W. Graepel, Azad Kumar, Syed Moin, Jeffrey C. Boyington, Gwo Yu Chuang, Cinque Soto, Ulrich Baxa, Arjen Q. Bakker, Hergen SpitsTim Beaumont, Zizheng Zheng, Ningshao Xia, Sung Youl Ko, John Paul Todd, Srinivas Rao, Barney S. Graham, Peter D. Kwong

Research output: Contribution to journalArticlepeer-review

445 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)592-598
Number of pages7
Issue number6158
StatePublished - 2013
Externally publishedYes

ASJC Scopus subject areas

  • General


Dive into the research topics of 'Structure-based design of a fusion glycoprotein vaccine for respiratory syncytial virus'. Together they form a unique fingerprint.

Cite this