5tdg
Crystal structure of prefusion-stabilized bovine RSV F (DS-Cav1 variant: strain ATue51908)
Structural highlights
FunctionPublication Abstract from PubMedBovine 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. Protection of calves by a prefusion-stabilized bovine RSV F vaccine.,Zhang B, Chen L, Silacci C, Thom M, Boyington JC, Druz A, Joyce MG, Guzman E, Kong WP, Lai YT, Stewart-Jones GBE, Tsybovsky Y, Yang Y, Zhou T, Baxa U, Mascola JR, Corti D, Lanzavecchia A, Taylor G, Kwong PD NPJ Vaccines. 2017 Mar 8;2:7. doi: 10.1038/s41541-017-0005-9. PMID:29021918[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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