A highly stable prefusion RSV F vaccine derived from structural analysis of the fusion mechanism
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Open Access
- 3 September 2015
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Communications
- Vol. 6 (1), 8143
- https://doi.org/10.1038/ncomms9143
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.This publication has 36 references indexed in Scilit:
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