气候变化领域集成服务门户(CCPortal): De novo protein design enables the precise induction of RSV-neutralizing antibodies

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DOI	10.1126/science.aay5051
	De novo protein design enables the precise induction of RSV-neutralizing antibodies
	Sesterhenn F.; Yang C.; Bonet J.; Cramer J.T.; Wen X.; Wang Y.; Chiang C.-I.; Abriata L.A.; Kucharska I.; Castoro G.; Vollers S.S.; Galloux M.; Dheilly E.; Rosset S.; Corthésy P.; Georgeon S.; Villard M.; Richard C.-A.; Descamps D.; Delgado T.; Oricchio E.; Rameix-Welti M.-A.; Más V.; Ervin S.; Eléouët J.-F.; Riffault S.; Bates J.T.; Julien J.-P.; Li Y.; Jardetzky T.; Krey T.; Correia B.E.
发表日期	2020
ISSN	0036-8075
卷号	368 期号:6492
英文摘要	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. Copyright © 2020 The Authors,
关键词	algorithm antibody design neutralization protein vaccine Mus Primates Respiratory syncytial virus Rice stripe virus epitope fusion protein nanobody neutralizing antibody respiratory syncytial virus vaccine biology biosynthesis chemistry human Human respiratory syncytial virus immunology procedures protein conformation protein engineering protein motif Amino Acid Motifs Antibodies, Neutralizing Computational Biology Humans Immunodominant Epitopes Protein Conformation Protein Engineering Recombinant Fusion Proteins Respiratory Syncytial Virus Vaccines Respiratory Syncytial Virus, Human Single-Domain Antibodies
语种	英语
来源机构	Science
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/133497
推荐引用方式 GB/T 7714	Sesterhenn F.,Yang C.,Bonet J.,et al. De novo protein design enables the precise induction of RSV-neutralizing antibodies[J]. Science,2020,368(6492).
APA	Sesterhenn F..,Yang C..,Bonet J..,Cramer J.T..,Wen X..,...&Correia B.E..(2020).De novo protein design enables the precise induction of RSV-neutralizing antibodies.,368(6492).
MLA	Sesterhenn F.,et al."De novo protein design enables the precise induction of RSV-neutralizing antibodies".368.6492(2020).