eLife (Aug 2020)
Tailored design of protein nanoparticle scaffolds for multivalent presentation of viral glycoprotein antigens
- George Ueda,
- Aleksandar Antanasijevic,
- Jorge A Fallas,
- William Sheffler,
- Jeffrey Copps,
- Daniel Ellis,
- Geoffrey B Hutchinson,
- Adam Moyer,
- Anila Yasmeen,
- Yaroslav Tsybovsky,
- Young-Jun Park,
- Matthew J Bick,
- Banumathi Sankaran,
- Rebecca A Gillespie,
- Philip JM Brouwer,
- Peter H Zwart,
- David Veesler,
- Masaru Kanekiyo,
- Barney S Graham,
- Rogier W Sanders,
- John P Moore,
- Per Johan Klasse,
- Andrew B Ward,
- Neil P King,
- David Baker
Affiliations
- George Ueda
- ORCiD
- Department of Biochemistry, University of Washington, Seattle, United States; Institute for Protein Design, University of Washington, Seattle, United States
- Aleksandar Antanasijevic
- ORCiD
- 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
- Jorge A Fallas
- Department of Biochemistry, University of Washington, Seattle, United States; Institute for Protein Design, University of Washington, Seattle, United States
- William Sheffler
- Department of Biochemistry, University of Washington, Seattle, United States; Institute for Protein Design, University of Washington, Seattle, United States
- Jeffrey Copps
- 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
- Daniel Ellis
- Department of Biochemistry, University of Washington, Seattle, United States; Institute for Protein Design, University of Washington, Seattle, United States
- Geoffrey B Hutchinson
- Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, United States
- Adam Moyer
- Department of Biochemistry, University of Washington, Seattle, United States; Institute for Protein Design, University of Washington, Seattle, United States
- Anila Yasmeen
- Department of Microbiology and Immunology, Weill Cornell Medicine, Cornell University, New York, United States
- Yaroslav Tsybovsky
- Electron Microscopy Laboratory, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research sponsored by the National Cancer Institute, Frederick, United States
- Young-Jun Park
- Department of Biochemistry, University of Washington, Seattle, United States
- Matthew J Bick
- ORCiD
- Department of Biochemistry, University of Washington, Seattle, United States; Institute for Protein Design, University of Washington, Seattle, United States
- Banumathi Sankaran
- Berkeley Center for Structural Biology, Molecular Biophysics and Integrated Bioimaging, Lawrence Berkeley Laboratory, Berkeley, United States
- Rebecca A Gillespie
- Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, United States
- Philip JM Brouwer
- ORCiD
- Amsterdam UMC, Department of Medical Microbiology, Amsterdam Infection & Immunity Institute, University of Amsterdam, Amsterdam, Netherlands
- Peter H Zwart
- Berkeley Center for Structural Biology, Molecular Biophysics and Integrated Bioimaging, Lawrence Berkeley Laboratory, Berkeley, United States; Center for Advanced Mathematics in Energy Research Applications, Computational Research Division, Lawrence Berkeley Laboratory, Berkeley, United States
- David Veesler
- ORCiD
- Department of Biochemistry, University of Washington, Seattle, United States
- Masaru Kanekiyo
- Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, United States
- Barney S Graham
- ORCiD
- Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, United States
- Rogier W Sanders
- Department of Microbiology and Immunology, Weill Cornell Medicine, Cornell University, New York, United States; Amsterdam UMC, Department of Medical Microbiology, Amsterdam Infection & Immunity Institute, University of Amsterdam, Amsterdam, Netherlands
- John P Moore
- Department of Microbiology and Immunology, Weill Cornell Medicine, Cornell University, New York, United States
- Per Johan Klasse
- ORCiD
- Department of Microbiology and Immunology, Weill Cornell Medicine, Cornell University, New York, United States
- Andrew B Ward
- ORCiD
- 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
- Neil P King
- Department of Biochemistry, University of Washington, Seattle, United States; Institute for Protein Design, University of Washington, Seattle, United States
- David Baker
- ORCiD
- Department of Biochemistry, University of Washington, Seattle, United States; Institute for Protein Design, University of Washington, Seattle, United States; Howard Hughes Medical Institute, University of Washington, Seattle, United States
- DOI
- https://doi.org/10.7554/eLife.57659
- Journal volume & issue
-
Vol. 9
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.
Keywords
