
Open access
Author
Zhang, Baoshan
Chen, Lei
Silacci, Chiara
Thom, Michelle
Boyington, Jeffrey C.
Druz, Aliaksandr
Joyce, M. Gordon
Guzman, Efrain
Kong, Wing-Pui
Lai, Yen-Ting
Stewart-Jones, Guillaume B.E.
Tsybovsky, Yaroslav
Yang, Yongping
Zhou, Tongqing
Baxa, Ulrich
Mascola, John R.
Corti, Davide
Lanzavecchia, Antonio
Taylor, Geraldine
Kwong, Peter D.
Date
2017Type
- Journal Article
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. Show more
Permanent link
https://doi.org/10.3929/ethz-b-000220116Publication status
publishedJournal / series
NPJ VACCINESVolume
Pages / Article No.
Publisher
Nature Publishing GroupMore
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