Fabian Sesterhenn; Che Yang; Jaume Bonet; Johannes 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 Richard; Delphyne Descamps; Teresa Delgado; Elisa Oricchio; Marie‐Anne Rameix‐Welti; Vicente Más; Sean Ervin; Jean‐François Eléouët; Sabine Riffault; John T. Bates; Jean‐Philippe Julien; Yuxing Li; Theodore S. Jardetzky; Thomas Krey; Bruno E. Correia · 2020 · Science
Paper
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.
Analysis
A novel protein design algorithm, TopoBuilder, was used to engineer epitope-focused immunogens that successfully induced robust neutralizing antibody responses against Respiratory Syncytial Virus (RSV) in mice and nonhuman primates.
Discovery
Anastassia A. Vorobieva; Rituparna Samanta; Toon Van Thillo
Laxmikant Gadhe; Katerina Konstantoulea; Aneesh Mazumder; Jie Chen; Lukasz A. Joachimiak; Nikolas Louros
Shaotong Luo; Bo Zhou
Maximilian Brackmann; Sophie Reiners; Masja Hoogendoorn; Michel Moser
Hoda M. Hammad; Anna M. Duraj‐Thatte
Jakob Agamia; Martin Zacharias
Source record