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Science. 2013 Nov 1;342(6158):592-8. doi: 10.1126/science.1243283.

Structure-based design of a fusion glycoprotein vaccine for respiratory syncytial virus.

Author information

1
Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.

Erratum in

  • Science. 2013 Nov 22;342(6161):931.

Abstract

Respiratory syncytial virus (RSV) is the leading cause of hospitalization for children under 5 years of age. We sought to engineer a viral antigen that provides greater protection than currently available vaccines and focused on antigenic site Ø, a metastable site specific to the prefusion state of the RSV fusion (F) glycoprotein, as this site is targeted by extremely potent RSV-neutralizing antibodies. Structure-based design yielded stabilized versions of RSV F that maintained antigenic site Ø when exposed to extremes of pH, osmolality, and temperature. Six RSV F crystal structures provided atomic-level data on how introduced cysteine residues and filled hydrophobic cavities improved stability. Immunization with site Ø-stabilized variants of RSV F in mice and macaques elicited levels of RSV-specific neutralizing activity many times the protective threshold.

PMID:
24179220
PMCID:
PMC4461862
DOI:
10.1126/science.1243283
[Indexed for MEDLINE]
Free PMC Article

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