Download MendeleyA highly stable prefusion RSV F vaccine derived from structural analysis of the fusion mechanism.
Krarup, A., Truan, D., Furmanova-Hollenstein, P., Bogaert, L., Bouchier, P., Bisschop, I.J., Widjojoatmodjo, M.N., Zahn, R., Schuitemaker, H., McLellan, J.S., Langedijk, J.P.(2015) Nat Commun 6: 8143-8143
- PubMed: 26333350
- DOI: https://doi.org/10.1038/ncomms9143
- Primary Citation of Related Structures:
5C69, 5C6B - PubMed 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.
Organizational Affiliation:
Janssen Infectious Diseases and Vaccines, Archimedesweg 4-6, Leiden 2333 CN, The Netherlands.
