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 |
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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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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.</description><identifier>ISSN: 2045-2322</identifier><identifier>EISSN: 2045-2322</identifier><identifier>DOI: 10.1038/srep34108</identifier><identifier>PMID: 27682426</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>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</subject><ispartof>Scientific reports, 2016-09, Vol.6 (1), p.34108-34108, Article 34108</ispartof><rights>The Author(s) 2016</rights><rights>Copyright Nature Publishing Group Sep 2016</rights><rights>Copyright © 2016, The Author(s) 2016 The Author(s)</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c504t-86e3be15edde5984fd584e9cbbd65f7830848472a3fb9e1159865acaefa2fb663</citedby><cites>FETCH-LOGICAL-c504t-86e3be15edde5984fd584e9cbbd65f7830848472a3fb9e1159865acaefa2fb663</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5040956/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5040956/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,315,728,781,785,865,886,27929,27930,41125,42194,51581,53796,53798</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27682426$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Killikelly, April M.</creatorcontrib><creatorcontrib>Kanekiyo, Masaru</creatorcontrib><creatorcontrib>Graham, Barney S.</creatorcontrib><title>Pre-fusion F is absent on the surface of formalin-inactivated respiratory syncytial virus</title><title>Scientific reports</title><addtitle>Sci Rep</addtitle><addtitle>Sci Rep</addtitle><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. 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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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