De novo protein design enables the precise induction of RSV-neutralizing antibodies

• DOI: 10.1126/science.aay5051
• Publication Date: 2020-05-14T23:09:47Z
• Authors: Fabian Sesterhenn; Che Yang; Jaume Bonet; Johannes T. Cramer; Xiaolin Wen; Yimeng Wang; Chi-I Chiang; Luciano A. Abriata; Iga Kucharska; Giacomo Castoro; Sabrina S. Vollers; Marie Galloux; Elie Dheilly; Stéphane Rosset; Patricia Corthésy; Sandrine Georgeon; Mélanie Villard; Charles-Adrien Ri...; Delphyne Descamps; Teresa Delgado; Elisa Oricchio; Marie-Anne Rameix...; Vicente Más; Sean Ervin; Jean-François Elé...; Sabine Riffault; John T. Bates; Jean-Philippe Julien; Yuxing Li; Theodore Jardetzky; Thomas Krey; Bruno E. Correia
• Keywords: Protein design

De novo protein design has been successful in expanding the natural repertoire. However, most de proteins lack biological function, presenting a major methodological challenge. In vaccinology, induction of precise antibody responses remains cornerstone for next-generation vaccines. Here, we present algorithm called TopoBuilder, with which engineered epitope-focused immunogens displaying complex structural motifs. both mice and nonhuman primates, cocktails three novo-designed induced robust neutralizing against respiratory syncytial virus. Furthermore, refocused preexisting toward defined neutralization epitopes. Overall, our approach opens possibility targeting specific epitopes development vaccines therapeutic antibodies and, more generally, will be applicable to functional