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. 2017-03-08 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. application/pdf https://susi.usi.ch/global/documents/319064 https://localhost:5000/ark:/12658/srd1319064 https://susi.usi.ch/documents/319064/files/Zhang_NPJV_2017.pdf eng info:eu-repo/semantics/altIdentifier/doi/10.1038/s41541-017-0005-9 info:eu-repo/semantics/altIdentifier/ark/12658/srd1319064 info:eu-repo/semantics/openAccess CC BY Npj vaccines. - 2017, vol. 2, p. 7 info:eu-repo/classification/udc/61 Protection of calves by a prefusion-stabilized bovine RSV F vaccine http://purl.org/coar/resource_type/c_6501