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Open AccessJournal ArticleDOI

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

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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

Fusing safety and efficacy: A maternal bivalent RSV prefusion F vaccine

TL;DR: Kampmann et al. as discussed by the authors demonstrated safety and efficacy of a maternal bivalent RSV prefusion F vaccine in reducing severe RSV-associated lower respiratory tract infections in infants at 90 and 180 days following birth.

Pöördvaktsinoloogia ja struktuuribioloogia: uued võtted vaktsiiniarenduses

Rein Sikut
TL;DR: Klassikalised pohimotted vaktsinoloogias formuleeris 19. sajandi lopul L. Pasteur as mentioned in this paper, see on andnud meile vaktiniine 27 haigustekitaja vastu ning viinud paljude nakkushaiguste leviku olulise vahenemiseni.
Journal ArticleDOI

Promising New Approach to Vaccine for Respiratory Syncytial Virus

TL;DR: Respiratory syncytial virus (RSV) is an important cause of death in neonates and elders and more than 3 million young children are hospitalized globally.
Journal ArticleDOI

Systematic conformation-to-phenotype mapping via limited deep sequencing of proteins.

TL;DR: In this paper , the authors carried out double-Cys mutational scanning of E. coli periplasmic chaperone HdeA to identify disordered hydrophobic conformers with variable cytotoxicity.
References
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Book ChapterDOI

Processing of X-ray diffraction data collected in oscillation mode

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.

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

Phaser crystallographic software

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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