In:
Science, American Association for the Advancement of Science (AAAS), Vol. 368, No. 6492 ( 2020-05-15)
Kurzfassung:
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.
Materialart:
Online-Ressource
ISSN:
0036-8075
,
1095-9203
DOI:
10.1126/science.aay5051
Sprache:
Englisch
Verlag:
American Association for the Advancement of Science (AAAS)
Publikationsdatum:
2020
ZDB Id:
128410-1
ZDB Id:
2066996-3
ZDB Id:
2060783-0
SSG:
11
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