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dc.contributor.author
Zhang, Baoshan
dc.contributor.author
Chen, Lei
dc.contributor.author
Silacci, Chiara
dc.contributor.author
Thom, Michelle
dc.contributor.author
Boyington, Jeffrey C.
dc.contributor.author
Druz, Aliaksandr
dc.contributor.author
Joyce, M. Gordon
dc.contributor.author
Guzman, Efrain
dc.contributor.author
Kong, Wing-Pui
dc.contributor.author
Lai, Yen-Ting
dc.contributor.author
Stewart-Jones, Guillaume B.E.
dc.contributor.author
Tsybovsky, Yaroslav
dc.contributor.author
Yang, Yongping
dc.contributor.author
Zhou, Tongqing
dc.contributor.author
Baxa, Ulrich
dc.contributor.author
Mascola, John R.
dc.contributor.author
Corti, Davide
dc.contributor.author
Lanzavecchia, Antonio
dc.contributor.author
Taylor, Geraldine
dc.contributor.author
Kwong, Peter D.
dc.date.accessioned
2018-02-02T14:38:43Z
dc.date.available
2017-12-12T05:43:08Z
dc.date.available
2018-02-02T14:38:43Z
dc.date.issued
2017
dc.identifier.other
10.1038/s41541-017-0005-9
en_US
dc.identifier.uri
http://hdl.handle.net/20.500.11850/220116
dc.identifier.doi
10.3929/ethz-b-000220116
dc.description.abstract
Bovine respiratory syncytial virus, a major cause of respiratory disease in calves, is closely related to human RSV, a leading cause of respiratory disease in infants. Recently, promising human RSV-vaccine candidates have been engineered that stabilize the metastable fusion (F) glycoprotein in its prefusion state; however, the absence of a relevant animal model for human RSV has complicated assessment of these vaccine candidates. Here, we use a combination of structure-based design, antigenic characterization, and X-ray crystallography to translate human RSV F stabilization into the bovine context. A “DS2” version of bovine respiratory syncytial virus F with subunits covalently fused, fusion peptide removed, and pre-fusion conformation stabilized by cavity-filling mutations and intra- and inter-protomer disulfides was recognized by pre-fusion-specific antibodies, AM14, D25, and MPE8, and elicited bovine respiratory syncytial virus-neutralizing titers in calves >100-fold higher than those elicited by post-fusion F. When challenged with a heterologous bovine respiratory syncytial virus, virus was not detected in nasal secretions nor in respiratory tract samples of DS2-immunized calves; by contrast bovine respiratory syncytial virus was detected in all post-fusion- and placebo-immunized calves. Our results demonstrate proof-of-concept that DS2-stabilized RSV F immunogens can induce highly protective immunity from RSV in a native host with implications for the efficacy of prefusion-stabilized F vaccines in humans and for the prevention of bovine respiratory syncytial virus in calves.
en_US
dc.format
application/pdf
en_US
dc.language.iso
en
en_US
dc.publisher
Nature Publishing Group
en_US
dc.rights.uri
http://creativecommons.org/licenses/by/4.0/
dc.title
Protection of calves by a prefusion-stabilized bovine RSV F vaccine
en_US
dc.type
Journal Article
dc.rights.license
Creative Commons Attribution 4.0 International
dc.date.published
2017-03-08
ethz.journal.title
NPJ VACCINES
ethz.journal.volume
2
en_US
ethz.pages.start
7
en_US
ethz.size
11 p.
en_US
ethz.version.deposit
publishedVersion
en_US
ethz.identifier.wos
ethz.publication.place
London
en_US
ethz.publication.status
published
en_US
ethz.date.deposited
2017-12-12T05:43:11Z
ethz.source
WOS
ethz.eth
yes
en_US
ethz.availability
Open access
en_US
ethz.rosetta.installDate
2018-02-02T14:38:50Z
ethz.rosetta.lastUpdated
2018-08-03T04:31:03Z
ethz.rosetta.versionExported
true
ethz.COinS
ctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.atitle=Protection%20of%20calves%20by%20a%20prefusion-stabilized%20bovine%20RSV%20F%20vaccine&rft.jtitle=NPJ%20VACCINES&rft.date=2017&rft.volume=2&rft.spage=7&rft.au=Zhang,%20Baoshan&Chen,%20Lei&Silacci,%20Chiara&Thom,%20Michelle&Boyington,%20Jeffrey%20C.&rft.genre=article&
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