Protection of calves by a prefusion-stabilized bovine RSV F vaccine

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.

doi:10.1038/s41541-017-0005-9

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Journal article

Protection of calves by a prefusion-stabilized bovine RSV F vaccine

Zhang, Baoshan Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA
Chen, Lei Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA
Silacci, Chiara Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
Thom, Michelle The Pirbright Institute, Ash Road, Pirbright, Woking, Surrey GU24 0NF, UK
Boyington, Jeffrey C. Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA
Druz, Aliaksandr Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA
Joyce, M. Gordon Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA
Guzman, Efrain The Pirbright Institute, Ash Road, Pirbright, Woking, Surrey GU24 0NF, UK
Kong, Wing-Pui Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA
Lai, Yen-Ting Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA
Stewart-Jones, Guillaume B. E. Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA
Tsybovsky, Yaroslav Electron Microscopy Laboratory, Cancer Research Technology Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD, USA
Yang, Yongping Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA
Zhou, Tongqing Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA
Baxa, Ulrich Electron Microscopy Laboratory, Cancer Research Technology Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD, USA
Mascola, John R. Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA
Corti, Davide Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland - Humabs BioMed SA, Via Mirasole 1, 6500 Bellinzona, Switzerland
Lanzavecchia, Antonio Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland - Institute for Microbiology, ETH Zurich, Wolfgang-Pauli-Strasse 10, 8093 Zurich, Switzerland
Taylor, Geraldine The Pirbright Institute, Ash Road, Pirbright, Woking, Surrey GU24 0NF, UK
Kwong, Peter D. Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA

08.03.2017

Published in:

Npj vaccines. - 2017, vol. 2, p. 7

English 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.

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