De novo protein design enables the precise induction of RSV-neutralizing antibodies-Reference-Cited by-同舟云学术

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

Published:2020-05-15 Issue:6492 Volume:368 Page:
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Sesterhenn Fabian¹²^ORCID,Yang Che¹²^ORCID,Bonet Jaume¹²^ORCID,Cramer Johannes T.³^ORCID,Wen Xiaolin⁴^ORCID,Wang Yimeng⁵^ORCID,Chiang Chi-I⁵,Abriata Luciano A.¹²^ORCID,Kucharska Iga⁶⁷,Castoro Giacomo³,Vollers Sabrina S.¹²^ORCID,Galloux Marie⁸,Dheilly Elie⁹,Rosset Stéphane¹²^ORCID,Corthésy Patricia¹²,Georgeon Sandrine¹²^ORCID,Villard Mélanie¹²^ORCID,Richard Charles-Adrien⁸,Descamps Delphyne⁸^ORCID,Delgado Teresa¹⁰,Oricchio Elisa⁹^ORCID,Rameix-Welti Marie-Anne¹¹^ORCID,Más Vicente¹⁰,Ervin Sean¹²^ORCID,Eléouët Jean-François⁸^ORCID,Riffault Sabine⁸,Bates John T.¹³^ORCID,Julien Jean-Philippe⁶⁷^ORCID,Li Yuxing⁵¹⁴,Jardetzky Theodore⁴^ORCID,Krey Thomas³¹⁵¹⁶¹⁷¹⁸^ORCID,Correia Bruno E.¹²^ORCID

Affiliation:

1. Institute of Bioengineering, École Polytechnique Fédérale de Lausanne, Lausanne CH-1015, Switzerland.

2. Swiss Institute of Bioinformatics (SIB), Lausanne CH-1015, Switzerland.

3. Institute of Virology, Hannover Medical School, Hannover 30625, Germany.

4. Department of Structural Biology, Stanford University School of Medicine, Stanford, CA 94305, USA.

5. Institute for Bioscience and Biotechnology Research, University of Maryland, Rockville, MD 20850, USA.

6. Program in Molecular Medicine, Hospital for Sick Children Research Institute, Toronto, Ontario M5G 0A4, Canada.

7. Departments of Biochemistry and Immunology, University of Toronto, Toronto, Ontario M5S 1A8, Canada.

8. Université Paris-Saclay, INRAE, UVSQ, VIM, 78350 Jouy-en-Josas, France.

9. Swiss Institute for Experimental Cancer Research, School of Life Sciences, École Polytechnique Fédérale de Lausanne, Lausanne CH-1015, Switzerland.

10. Centro Nacional de Microbiología, Instituto de Salud Carlos III, 28220 Madrid, Spain.

11. UMR1173, INSERM, Université de Versailles St. Quentin, 78180 Montigny le Bretonneux, France.

12. Wake Forest Baptist Medical Center, Winston Salem, NC 27157, USA.

13. University of Mississippi Medical Center, Jackson, MS 39216, USA.

14. Department of Microbiology and Immunology & Center of Biomolecular Therapeutics, University of Maryland School of Medicine, Baltimore, MD 21201, USA.

15. German Center for Infection Research (DZIF), 38124 Braunschweig, Germany.

16. Institute of Biochemistry, Center of Structural and Cell Biology in Medicine, University of Luebeck, D-23538 Luebeck, Germany.

17. Excellence Cluster 2155 RESIST, Hannover Medical School, 30625 Hannover, Germany.

18. Centre for Structural Systems Biology (CSSB), 22607 Hamburg, Germany.

Abstract

TopoBuilding precision vaccines To induce strong and targeted neutralizing antibody (nAb) responses against vaccine targets, one strategy has been to use computationally designed immunogens. However, the structural complexity of many known neutralization epitopes has posed a major challenge for the design of accurate epitope mimetics. Sesterhenn et al. created a protein design algorithm called TopoBuilder to design scaffolds for irregular and discontinuous neutralization epitopes. As a proof of principle, the authors generated epitope-focused immunogens based on the prefusion conformation of the respiratory syncytial virus (RSV) fusion protein. When these immunogens were used to vaccinate mice and nonhuman primates in RSV infection models, they generated targeted nAb responses to RSV and boosted site-specific nAb responses in heterologous prime-boost vaccination schemes. Science , this issue p. eaay5051

Funder

European Research Council

Swiss National Science Foundation

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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