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

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.

journal_name

Nat Commun

journal_title

Nature communications

authors

Krarup A,Truan D,Furmanova-Hollenstein P,Bogaert L,Bouchier P,Bisschop IJM,Widjojoatmodjo MN,Zahn R,Schuitemaker H,McLellan JS,Langedijk JPM

doi

10.1038/ncomms9143

subject

Has Abstract

pub_date

2015-09-03 00:00:00

pages

8143

issn

2041-1723

pii

ncomms9143

journal_volume

6

pub_type

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