Structure-based design of a fusion glycoprotein vaccine for respiratory syncytial virus.
Science
; 342(6158): 592-8, 2013 Nov 01.
Article
em En
| MEDLINE
| ID: mdl-24179220
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Glicoproteínas
/
Proteínas Virais de Fusão
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Infecções por Vírus Respiratório Sincicial
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Vacinas contra Vírus Sincicial Respiratório
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Antígenos Virais
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article