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Tailored design of protein nanoparticle scaffolds for multivalent presentation of viral glycoprotein antigens

  1. Author:
    Ueda, George [ORCID]
    Antanasijevic, Aleksandar [ORCID]
    Fallas, Jorge A
    Sheffler, William
    Copps, Jeffrey
    Ellis, Daniel
    Hutchinson, Geoffrey B
    Moyer, Adam
    Yasmeen, Anila
    Tsybovsky,Yaroslav
    Park, Young-Jun
    Bick, Matthew J [ORCID]
    Sankaran, Banumathi
    Gillespie, Rebecca A
    Brouwer, Philip Jm [ORCID]
    Zwart, Peter H
    Veesler, David [ORCID]
    Kanekiyo, Masaru
    Graham, Barney S [ORCID]
    Sanders, Rogier W
    Moore, John P
    Klasse, Per Johan [ORCID]
    Ward, Andrew B [ORCID]
    King, Neil P
    Baker, David [ORCID]

  2. Author Address

    Department of Biochemistry, University of Washington, Seattle, United States., Institute for Protein Design, University of Washington, Seattle, United States., Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, United States., International AIDS Vaccine Initiative Neutralizing Antibody Center, the Collaboration for AIDS Vaccine Discovery (CAVD) and Scripps Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, United States., Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, United States., Department of Microbiology and Immunology, Weill Cornell Medicine, Cornell University, New York, United States., Electron Microscopy Laboratory, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research sponsored by the National Cancer Institute, Frederick, United States., Berkeley Center for Structural Biology, Molecular Biophysics and Integrated Bioimaging, Lawrence Berkeley Laboratory, Berkeley, United States., Amsterdam UMC, Department of Medical Microbiology, Amsterdam Infection & Immunity Institute, University of Amsterdam, Amsterdam, Netherlands., Center for Advanced Mathematics in Energy Research Applications, Computational Research Division, Lawrence Berkeley Laboratory, Berkeley, United States., Howard Hughes Medical Institute, University of Washington, Seattle, United States.,
    1. Year: 2020
    2. Date: Aug 04
    3. Epub Date: 2020 08 04
  2. Journal: eLife
    1. 9
    2. Pages: pii: 9:e57659
  4. Type of Article: Article
  5. Article Number: e57659
  1. Abstract:

    Multivalent presentation of viral glycoproteins can substantially increase the elicitation of antigen-specific antibodies. To enable a new generation of anti-viral vaccines, we designed self-assembling protein nanoparticles with geometries tailored to present the ectodomains of influenza, HIV, and RSV viral glycoprotein trimers. We first de novo designed trimers tailored for antigen fusion, featuring N-terminal helices positioned to match the C termini of the viral glycoproteins. Trimers that experimentally adopted their designed configurations were incorporated as components of tetrahedral, octahedral, and icosahedral nanoparticles, which were characterized by cryo-electron microscopy and assessed for their ability to present viral glycoproteins. Electron microscopy and antibody binding experiments demonstrated that the designed nanoparticles presented antigenically intact prefusion HIV-1 Env, influenza hemagglutinin, and RSV F trimers in the predicted geometries. This work demonstrates that antigen-displaying protein nanoparticles can be designed from scratch, and provides a systematic way to investigate the influence of antigen presentation geometry on the immune response to vaccination.

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External Sources

  1. View Full Text
  2. DOI: 10.7554/eLife.57659
  3. PMID: 32748788
  4. View record in Web of Science®
  5. WOS: 000558731200001
  6. PII : 57659

Library Notes

  1. Fiscal Year: FY2019-2020
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