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Open AccessJournal ArticleDOI

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

Jason S. McLellan, +27 more
- 01 Nov 2013 - 
- Vol. 342, Iss: 6158, pp 592-598
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TLDR
A viral antigen is sought 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.
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 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.

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Journal ArticleDOI

Chemotherapy of respiratory syncytial virus infections: the final breakthrough.

Erik De Clercq
- 01 Mar 2015 - 
TL;DR: A new antiviral, GS-5806, which interferes with virus–cell fusion, has proven efficacious in experimental RSV infections in adults.
Journal ArticleDOI

Antibody Epitopes of Pneumovirus Fusion Proteins.

Jiachen Huang, +2 more
- 29 Nov 2019 - 
TL;DR: Overall, this review will cover recent advances in characterizing the antigenic sites on the RSV and hMPV F proteins.
Journal ArticleDOI

Structure-based design of ferritin nanoparticle immunogens displaying antigenic loops of Neisseria gonorrhoeae .

Liqin Wang, +4 more
- 24 Jul 2017 - 
TL;DR: The results confirmed that the ferritin nanoparticle is a robust platform to present antigenic peptides and therefore an ideal system for rational design of immunogens.
Journal ArticleDOI

Increasing Complexity of Vaccine Development.

Stanley A. Plotkin
- 15 Jul 2015 - 
TL;DR: The development of future vaccines requires solution of a number of immunologic problems, including pathogen variability, short effector memory, evoking functional responses, and identification of antigens that generate protective responses.
Journal ArticleDOI

Induction of high titred, non-neutralising antibodies by self-adjuvanting peptide epitopes derived from the respiratory syncytial virus fusion protein

Noushin Jaberolansar, +6 more
- 11 Sep 2017 - 
TL;DR: A vaccine strategy that utilises a lipid core peptide (LCP) delivery system with self-adjuvanting properties in conjunction with either the antigenic site Ø or II (B cell epitopes) along with PADRE as a T helper cell epitope is reported.
References
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Book ChapterDOI

Processing of X-ray diffraction data collected in oscillation mode

Zbyszek Otwinowski, +1 more
- 01 Jan 1997 - 
TL;DR: The methods presented in the chapter have been applied to solve a large variety of problems, from inorganic molecules with 5 A unit cell to rotavirus of 700 A diameters crystallized in 700 × 1000 × 1400 A cell.
Journal ArticleDOI

Features and development of Coot.

Paul Emsley, +3 more
- 01 Apr 2010 - 
TL;DR: Coot is a molecular-graphics program designed to assist in the building of protein and other macromolecular models and the current state of development and available features are presented.
Journal ArticleDOI

PHENIX: a comprehensive Python-based system for macromolecular structure solution

Paul D. Adams, +18 more
- 01 Feb 2010 - 
TL;DR: The PHENIX software for macromolecular structure determination is described and its uses and benefits are described.
Journal ArticleDOI

Phaser crystallographic software

Airlie J. McCoy, +5 more
- 01 Aug 2007 - 
TL;DR: A description is given of Phaser-2.1: software for phasing macromolecular crystal structures by molecular replacement and single-wavelength anomalous dispersion phasing.
Journal ArticleDOI

Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010

Rafael Lozano, +195 more
- 15 Dec 2012 - 
TL;DR: The Global Burden of Diseases, Injuries, and Risk Factors Study 2010 aimed to estimate annual deaths for the world and 21 regions between 1980 and 2010 for 235 causes, with uncertainty intervals (UIs), separately by age and sex, using the Cause of Death Ensemble model.
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