Boosting subdominant neutralizing antibody responses with a computationally designed epitope-focused immunogen.
PLoS Biol
; 17(2): e3000164, 2019 02.
Article
em En
| MEDLINE
| ID: mdl-30789898
ABSTRACT
Throughout the last several decades, vaccination has been key to prevent and eradicate infectious diseases. However, many pathogens (e.g., respiratory syncytial virus [RSV], influenza, dengue, and others) have resisted vaccine development efforts, largely because of the failure to induce potent antibody responses targeting conserved epitopes. Deep profiling of human B cells often reveals potent neutralizing antibodies that emerge from natural infection, but these specificities are generally subdominant (i.e., are present in low titers). A major challenge for next-generation vaccines is to overcome established immunodominance hierarchies and focus antibody responses on crucial neutralization epitopes. Here, we show that a computationally designed epitope-focused immunogen presenting a single RSV neutralization epitope elicits superior epitope-specific responses compared to the viral fusion protein. In addition, the epitope-focused immunogen efficiently boosts antibodies targeting the palivizumab epitope, resulting in enhanced neutralization. Overall, we show that epitope-focused immunogens can boost subdominant neutralizing antibody responses in vivo and reshape established antibody hierarchies.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Vírus Sinciciais Respiratórios
/
Proteínas Recombinantes de Fusão
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Receptores de Antígenos de Linfócitos B
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Proteínas Virais de Fusão
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Anticorpos Neutralizantes
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Anticorpos Antivirais
/
Epitopos
Idioma:
En
Revista:
PLoS Biol
Assunto da revista:
BIOLOGIA
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Suíça