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

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  • 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

    (University of Maryland [Baltimore])

  • Chi I. Chiang

    (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] - ISC - 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] - ISC - 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

    (University of Maryland [Baltimore], University of Maryland School of Medicine - University of Maryland System)

  • 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)

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

Suggested Citation

  • 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 Gall, 2020. "De novo protein design enables the precise induction of RSV-neutralizing antibodies," Post-Print hal-02677103, HAL.
  • Handle: RePEc:hal:journl:hal-02677103
    DOI: 10.1126/science.aay5051
    Note: View the original document on HAL open archive server: https://hal.science/hal-02677103
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    1. Betz, Ulrich A.K. & Arora, Loukik & Assal, Reem A. & Azevedo, Hatylas & Baldwin, Jeremy & Becker, Michael S. & Bostock, Stefan & Cheng, Vinton & Egle, Tobias & Ferrari, Nicola & Schneider-Futschik, El, 2023. "Game changers in science and technology - now and beyond," Technological Forecasting and Social Change, Elsevier, vol. 193(C).
    2. Robert J. Ragotte & David Pulido & Amelia M. Lias & Doris Quinkert & Daniel G. W. Alanine & Abhishek Jamwal & Hannah Davies & Adéla Nacer & Edward D. Lowe & Geoffrey W. Grime & Joseph J. Illingworth &, 2022. "Heterotypic interactions drive antibody synergy against a malaria vaccine candidate," Nature Communications, Nature, vol. 13(1), pages 1-12, December.

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