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oai:repisalud.isciii.es:20.500.12105/141072024-09-27T19:59:14Zcom_20.500.12105_2052com_20.500.12105_2051col_20.500.12105_19609

00925njm 22002777a 4500 dc Sesterhenn, Fabian author Yang, Che author Bonet, Jaume author Cramer, Johannes T author Wen, Xiaolin author Wang, Yimeng author Chiang, Chi-I author Abriata, Luciano A author Kucharska, Iga author Castoro, Giacomo author Vollers, Sabrina S author Galloux, Marie author Dheilly, Elie author Rosset, Stéphane author Corthésy, Patricia author Georgeon, Sandrine author Villard, Mélanie author Richard, Charles-Adrien author Descamps, Delphyne author Delgado-Romero, Teresa author Oricchio, Elisa author Rameix-Welti, Marie-Anne author Mas-Lloret, Vicente author Ervin, Sean author Eléouët, Jean-François author Riffault, Sabine author Bates, John T author Julien, Jean-Philippe author Li, Yuxing author Jardetzky, Theodore author Krey, Thomas author Correia, Bruno E author 2020 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. Science. 2020 May 15;368(6492):eaay5051. 10.1126/science.aay5051 1095-9203 Science (New York, N.Y.) 32409444 http://hdl.handle.net/20.500.12105/14107 De novo protein design enables the precise induction of RSV-neutralizing antibodies