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

Fabian Sesterhenn, Che Yang, Jaume Bonet, Johannes T. Cramer, Xiaolin Wen, Yimeng Wang, Chi I. Chiang, Luciano Andres 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 Francois Eleouet (), Sabine Riffault (), John T. Bates, Jean Philippe Julien, Yuxing Li, Theodore S. Jardetzky, Thomas Krey and Bruno Correia
Additional contact information
Fabian Sesterhenn: EPFL - Ecole Polytechnique Fédérale de Lausanne, SIB - Swiss Institute of Bioinformatics [Lausanne] - UNIL - Université de Lausanne = University of Lausanne
Che Yang: EPFL - Ecole Polytechnique Fédérale de Lausanne, SIB - Swiss Institute of Bioinformatics [Lausanne] - UNIL - Université de Lausanne = University of Lausanne
Jaume Bonet: EPFL - Ecole Polytechnique Fédérale de Lausanne, SIB - Swiss Institute of Bioinformatics [Lausanne] - UNIL - Université de Lausanne = University of Lausanne
Johannes T. Cramer: MHH - Medizinische Hochschule Hannover = Hannover Medical School
Xiaolin Wen: Stanford School of Medicine [Stanford] - Stanford Medicine - Stanford University
Yimeng Wang: UMB - University of Maryland [Baltimore]
Chi I. Chiang: UMB - University of Maryland [Baltimore]
Luciano Andres Abriata: EPFL - Ecole Polytechnique Fédérale de Lausanne, SIB - Swiss Institute of Bioinformatics [Lausanne] - UNIL - Université de Lausanne = University of Lausanne
Iga Kucharska: SickKids - The Hospital for sick children [Toronto], Department of Biochemistry [University of Toronto] - University of Toronto
Giacomo Castoro: MHH - Medizinische Hochschule Hannover = Hannover Medical School
Sabrina S. Vollers: EPFL - Ecole Polytechnique Fédérale de Lausanne, SIB - Swiss Institute of Bioinformatics [Lausanne] - UNIL - Université de Lausanne = University of Lausanne
Marie Galloux: VIM (UR 0892) - Virologie et Immunologie Moléculaires - UVSQ - Université de Versailles Saint-Quentin-en-Yvelines - Université Paris-Saclay - INRAE - Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement
Elie Dheilly: ISREC - Swiss Institute for Experimental Cancer Research - Lausanne - Swiss Institute for Experimental Cancer Research
Stéphane Rosset: EPFL - Ecole Polytechnique Fédérale de Lausanne, SIB - Swiss Institute of Bioinformatics [Lausanne] - UNIL - Université de Lausanne = University of Lausanne
Patricia Corthésy: EPFL - Ecole Polytechnique Fédérale de Lausanne, SIB - Swiss Institute of Bioinformatics [Lausanne] - UNIL - Université de Lausanne = University of Lausanne
Sandrine Georgeon: EPFL - Ecole Polytechnique Fédérale de Lausanne, SIB - Swiss Institute of Bioinformatics [Lausanne] - UNIL - Université de Lausanne = University of Lausanne
Mélanie Villard: EPFL - Ecole Polytechnique Fédérale de Lausanne, SIB - Swiss Institute of Bioinformatics [Lausanne] - UNIL - Université de Lausanne = University of Lausanne
Charles-Adrien Richard: VIM (UR 0892) - Virologie et Immunologie Moléculaires - UVSQ - Université de Versailles Saint-Quentin-en-Yvelines - Université Paris-Saclay - INRAE - Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement
Delphyne Descamps: VIM (UR 0892) - Virologie et Immunologie Moléculaires - UVSQ - Université de Versailles Saint-Quentin-en-Yvelines - Université Paris-Saclay - INRAE - Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement
Teresa Delgado: CNM - Centro Nacional de Microbiología [ISCIII, Madrid, Spain] - ISCIII - Instituto de Salud Carlos III [Madrid]
Elisa Oricchio: ISREC - Swiss Institute for Experimental Cancer Research - Lausanne - Swiss Institute for Experimental Cancer Research
Marie Anne Rameix-Welti: 2I - Infection et inflammation - UVSQ - Université de Versailles Saint-Quentin-en-Yvelines - INSERM - Institut National de la Santé et de la Recherche Médicale
Vicente Más: CNM - Centro Nacional de Microbiología [ISCIII, Madrid, Spain] - ISCIII - Instituto de Salud Carlos III [Madrid]
Sean Ervin: Wake Forest Baptist Medical Center
Jean Francois Eleouet: VIM (UR 0892) - Virologie et Immunologie Moléculaires - UVSQ - Université de Versailles Saint-Quentin-en-Yvelines - Université Paris-Saclay - INRAE - Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement
Sabine Riffault: VIM (UR 0892) - Virologie et Immunologie Moléculaires - UVSQ - Université de Versailles Saint-Quentin-en-Yvelines - Université Paris-Saclay - INRAE - Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement
John T. Bates: UMMC - University of Mississippi Medical Center
Jean Philippe Julien: SickKids - The Hospital for sick children [Toronto], Department of Biochemistry [University of Toronto] - University of Toronto
Yuxing Li: UMB - University of Maryland [Baltimore], University of Maryland School of Medicine - University System of Maryland
Theodore S. Jardetzky: Stanford School of Medicine [Stanford] - Stanford Medicine - Stanford University
Thomas Krey: MHH - Medizinische Hochschule Hannover = Hannover Medical School, DZIF - German Center for Infection Research - partner site Hannover-Braunschweig, University of Luebeck - University of Luebeck, INSTITUT FUR ANGEWANDTE BODENBIOLOGIE GMBH HAMBURG DEU - Partenaires IRSTEA - IRSTEA - Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture
Bruno Correia: EPFL - Ecole Polytechnique Fédérale de Lausanne, SIB - Swiss Institute of Bioinformatics [Lausanne] - UNIL - Université de Lausanne = University of Lausanne

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Abstract: 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

Date: 2020
Note: View the original document on HAL open archive server: https://hal.science/hal-02677103v1
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Citations: View citations in EconPapers (2)

Published in Science, 2020, 368 (6492), ⟨10.1126/science.aay5051⟩

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Persistent link: https://EconPapers.repec.org/RePEc:hal:journl:hal-02677103

DOI: 10.1126/science.aay5051

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