Details

Autor(en) / Beteiligte

• Krarup, Anders
• Truan, Daphné
• Furmanova-Hollenstein, Polina
• Bogaert, Lies
• Bouchier, Pascale
• Bisschop, Ilona J M
• Widjojoatmodjo, Myra N
• Zahn, Roland
• Schuitemaker, Hanneke
• McLellan, Jason S
• Langedijk, Johannes P M

Titel

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

Ist Teil von

• Nature communications, 2015-09, Vol.6 (1), p.8143-8143, Article 8143

Ort / Verlag

England: Nature Publishing Group

Erscheinungsjahr

2015

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.