Pre-fusion F is absent on the surface of formalin-inactivated respiratory syncytial virus

The lack of a licensed vaccine for respiratory syncytial virus (RSV) can be partly attributed to regulatory hurdles resulting from vaccine enhanced respiratory disease (ERD) subsequent to natural RSV infection that was observed in clinical trials of formalin-inactivated RSV (FI-RSV) in antigen-naïve...

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Veröffentlicht in:Scientific reports 2016-09, Vol.6 (1), p.34108-34108, Article 34108
Hauptverfasser: Killikelly, April M., Kanekiyo, Masaru, Graham, Barney S.
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Kanekiyo, Masaru
Graham, Barney S.
description The lack of a licensed vaccine for respiratory syncytial virus (RSV) can be partly attributed to regulatory hurdles resulting from vaccine enhanced respiratory disease (ERD) subsequent to natural RSV infection that was observed in clinical trials of formalin-inactivated RSV (FI-RSV) in antigen-naïve infants. To develop an effective vaccine that does not enhance RSV illness, it is important to understand how formalin and heat inactivation affected the antigenicity and immunogenicity of FI-RSV compared to native virus. Informed by atomic structures of RSV fusion (F) glycoprotein in prefusion (pre-F) and postfusion (post-F) conformations, we demonstrate that FI-RSV predominately presents post-F on the virion surface, whereas infectious RSV presents both pre-F and post-F conformations. This significant antigenic distinction has not been previously appreciated. Thus, a stabilized pre-F antigen is more representative of live RSV than F in its post-F conformation, as displayed on the surface of FI-RSV. This finding has major implications for discriminating current pre-F-based immunogens from FI-RSV used in historical vaccine trials.
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subjects 631/250/590
631/250/590/2294
82
82/1
Antigenicity
Antigens
Clinical trials
Conformation
Formaldehyde
Heat inactivation
Humanities and Social Sciences
Immunogenicity
Inactivation
Infants
multidisciplinary
Respiratory diseases
Respiratory syncytial virus
Science
Vaccines
Virions
title Pre-fusion F is absent on the surface of formalin-inactivated respiratory syncytial virus
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