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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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Citations
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Journal ArticleDOI

Implications of the SARS-CoV-2 pandemic on the epidemiology of pediatric Respiratory Syncytial Virus (RSV) infection.

Oludare A. Odumade, +2 more
- 17 May 2022 - 
TL;DR: The implications of COVID-19 on RSV seasonality patterns and mitigation efforts, as well as the urgent need for vaccination as a preventative tool are discussed.

Structural characterization of the human immune response to the meningococcal vaccine antigen NHBA

Martina Maritan
TL;DR: A structural characterization of the first high-resolution crystal structures of three free human anti-NHBA Fabs ofNHBA reveal features compatible with the binding of NHBA regions as previously determined by other low-resolution methods.
Journal ArticleDOI

Murine Pneumonia Virus Expressing the Fusion Glycoprotein of Human Respiratory Syncytial Virus from an Added Gene Is Highly Attenuated and Immunogenic in Rhesus Macaques.

Linda G. Brock, +10 more
- 16 Aug 2018 - 
TL;DR: This study demonstrated that rMPV provides a highly attenuated yet immunogenic vector for the expression of RSV F protein, with potential application in RSV-naive andRSV-experienced populations.
Posted ContentDOI

Structure-based design of hepatitis C virus E2 glycoprotein improves serum binding and cross-neutralization

Brian G. Pierce, +18 more
- 17 Apr 2020 - 
TL;DR: Results indicate that antigen optimization through structure-based design of the envelope glycoproteins is a promising route to an effective vaccine for HCV.
Journal ArticleDOI

Chimeric single α-helical domains as rigid fusion protein connections for protein nanotechnology and structural biology

Gabriella Collu, +12 more
- 24 Sep 2021 - 
TL;DR: In this paper, a single α-helical domain (SAH) is fused to terminal helices of proteins, forming an extended, partially free-standing rigid helix, which enables the connection of two domains at a defined distance and orientation.
References
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Book ChapterDOI

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Zbyszek Otwinowski, +1 more
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Journal ArticleDOI

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Rafael Lozano, +195 more
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