A highly stable prefusion RSV F vaccine derived from structural analysis of the fusion mechanism.
Nat Commun
; 6: 8143, 2015 Sep 03.
Article
em En
| MEDLINE
| ID: mdl-26333350
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Vírus Sinciciais Respiratórios
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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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Anticorpos Neutralizantes
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Antígenos Virais
Limite:
Animals
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article