De novo protein design enables the precise induction of RSV-neutralizing antibodies.
Science
; 368(6492)2020 05 15.
Article
en En
| MEDLINE
| ID: mdl-32409444
ABSTRACT
De novo protein design has been successful in expanding the natural protein repertoire. However, most de novo proteins lack biological function, presenting a major methodological challenge. In vaccinology, the induction of precise antibody responses remains a cornerstone for next-generation vaccines. Here, we present a protein design algorithm called TopoBuilder, with which we engineered epitope-focused immunogens displaying complex structural motifs. In both mice and nonhuman primates, cocktails of three de novo-designed immunogens induced robust neutralizing responses against the respiratory syncytial virus. Furthermore, the immunogens refocused preexisting antibody responses toward defined neutralization epitopes. Overall, our design approach opens the possibility of targeting specific epitopes for the development of vaccines and therapeutic antibodies and, more generally, will be applicable to the design of de novo proteins displaying complex functional motifs.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Proteínas Recombinantes de Fusión
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Ingeniería de Proteínas
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Epítopos Inmunodominantes
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Virus Sincitial Respiratorio Humano
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Biología Computacional
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Vacunas contra Virus Sincitial Respiratorio
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Anticuerpos Neutralizantes
Límite:
Humans
Idioma:
En
Año:
2020
Tipo del documento:
Article