Structure-based design of a fusion glycoprotein vaccine for respiratory syncytial virus.
basic_science · Level V
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- Record sourced from PubMed, PMID 24179220.
- Also identified by DOI 10.1126/science.1243283 and PMC identifier 4461862.
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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.
Medical subject headings
- Antigens, Viral
- Glycoproteins
- Respiratory Syncytial Virus Infections
- Respiratory Syncytial Virus Vaccines
- Viral Fusion Proteins