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Nat Commun. 2015 Sep 3;6:8143. doi: 10.1038/ncomms9143.

A highly stable prefusion RSV F vaccine derived from structural analysis of the fusion mechanism.

Author information

1
Janssen Infectious Diseases and Vaccines, Archimedesweg 4-6, Leiden 2333 CN, The Netherlands.
2
Department of Biochemistry, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire 03755-3844, USA.

Abstract

Respiratory syncytial virus (RSV) causes acute lower respiratory tract infections and is the leading cause of infant hospitalizations. Recently, a promising vaccine antigen based on the RSV fusion protein (RSV F) stabilized in the native prefusion conformation has been described. Here we report alternative strategies to arrest RSV F in the prefusion conformation based on the prevention of hinge movements in the first refolding region and the elimination of proteolytic exposure of the fusion peptide. A limited number of unique mutations are identified that stabilize the prefusion conformation of RSV F and dramatically increase expression levels. This highly stable prefusion RSV F elicits neutralizing antibodies in cotton rats and induces complete protection against viral challenge. Moreover, the structural and biochemical analysis of the prefusion variants suggests a function for p27, the excised segment that precedes the fusion peptide in the polypeptide chain.

PMID:
26333350
PMCID:
PMC4569726
DOI:
10.1038/ncomms9143
[Indexed for MEDLINE]
Free PMC Article

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