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

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

Journal Article · Wed Mar 08 00:00:00 EST 2017 · npj Vaccines

DOI:https://doi.org/10.1038/s41541-017-0005-9· OSTI ID:1352244

Zhang, Baoshan ^[1]; Chen, Lei ^[1]; Silacci, Chiara ^[2]; Thom, Michelle ^[3]; Boyington, Jeffrey C. ^[1]; Druz, Aliaksandr ^[1]; Joyce, M. Gordon ^[1]; Guzman, Efrain ^[3]; Kong, Wing- Pui ^[1]; Lai, Yen-Ting ^[1]; Stewart-Jones, Guillaume B. E. ^[1]; Tsybovsky, Yaroslav ^[4]; Yang, Yongping ^[1]; Zhou, Tongqing ^[1]; Baxa, Ulrich ^[4]; Mascola, John R. ^[1]; Corti, Davide ^[5]; Lanzavecchia, Antonio ^[6]; Taylor, Geraldine ^[3]; Kwong, Peter D. ^[1]

National Inst. of Health (NIH), Bethesda, MD (United States)
Univ. della Svizzera Italiana, Bellinzona (Switzerland)
The Pirbright Inst., Surrey (United Kingdom)
Frederick National Lab. for Cancer Research, MD (United States)
Univ. della Svizzera Italiana, Bellinzona (Switzerland); Humabs BioMed SA, Bellinzona (Switzerland)
Univ. della Svizzera Italiana, Bellinzona (Switzerland); ETH Zurich (Switzerland)

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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Research Organization:: Argonne National Laboratory (ANL), Argonne, IL (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Basic Energy Sciences (BES); National Inst. of Health; National Inst. of Allergy and Infectious Diseases

Grant/Contract Number:: W-31-109-Eng-38

OSTI ID:: 1352244

Journal Information:: npj Vaccines, Vol. 2, Issue 1; ISSN 2059-0105

Country of Publication:: United States

Language:: ENGLISH

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Cited by: 34 works

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