Title |
Structure-Based Design of a Fusion Glycoprotein Vaccine for Respiratory Syncytial Virus
|
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Published in |
Science, November 2013
|
DOI | 10.1126/science.1243283 |
Pubmed ID | |
Authors |
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 Spits, Tim Beaumont, Zizheng Zheng, Ningshao Xia, Sung-Youl Ko, John-Paul Todd, Srinivas Rao, Barney S. Graham, Peter D. Kwong |
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. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
Japan | 12 | 16% |
United States | 10 | 14% |
United Kingdom | 5 | 7% |
Comoros | 2 | 3% |
Portugal | 1 | 1% |
Malaysia | 1 | 1% |
Austria | 1 | 1% |
Curaçao | 1 | 1% |
Turkey | 1 | 1% |
Other | 1 | 1% |
Unknown | 39 | 53% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 63 | 85% |
Scientists | 8 | 11% |
Science communicators (journalists, bloggers, editors) | 2 | 3% |
Practitioners (doctors, other healthcare professionals) | 1 | 1% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 6 | 1% |
United Kingdom | 4 | <1% |
Japan | 3 | <1% |
Ireland | 1 | <1% |
Israel | 1 | <1% |
Netherlands | 1 | <1% |
Taiwan | 1 | <1% |
Colombia | 1 | <1% |
Germany | 1 | <1% |
Other | 1 | <1% |
Unknown | 523 | 96% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 137 | 25% |
Researcher | 115 | 21% |
Student > Master | 48 | 9% |
Student > Bachelor | 39 | 7% |
Student > Doctoral Student | 25 | 5% |
Other | 74 | 14% |
Unknown | 105 | 19% |
Readers by discipline | Count | As % |
---|---|---|
Agricultural and Biological Sciences | 140 | 26% |
Biochemistry, Genetics and Molecular Biology | 107 | 20% |
Immunology and Microbiology | 63 | 12% |
Medicine and Dentistry | 46 | 8% |
Chemistry | 21 | 4% |
Other | 51 | 9% |
Unknown | 115 | 21% |