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Single-component multilayered self-assembling nanoparticles presenting rationally designed glycoprotein trimers as Ebola virus vaccines

Author

Listed:
  • Linling He

    (The Scripps Research Institute)

  • Anshul Chaudhary

    (The Scripps Research Institute)

  • Xiaohe Lin

    (The Scripps Research Institute)

  • Cindy Sou

    (The Scripps Research Institute)

  • Tanwee Alkutkar

    (The Scripps Research Institute)

  • Sonu Kumar

    (The Scripps Research Institute)

  • Timothy Ngo

    (The Scripps Research Institute)

  • Ezra Kosviner

    (The Scripps Research Institute)

  • Gabriel Ozorowski

    (The Scripps Research Institute)

  • Robyn L. Stanfield

    (The Scripps Research Institute)

  • Andrew B. Ward

    (The Scripps Research Institute)

  • Ian A. Wilson

    (The Scripps Research Institute
    The Scripps Research Institute)

  • Jiang Zhu

    (The Scripps Research Institute
    The Scripps Research Institute)

Abstract

Ebola virus (EBOV) glycoprotein (GP) can be recognized by neutralizing antibodies (NAbs) and is the main target for vaccine design. Here, we first investigate the contribution of the stalk and heptad repeat 1-C (HR1C) regions to GP metastability. Specific stalk and HR1C modifications in a mucin-deleted form (GPΔmuc) increase trimer yield, whereas alterations of HR1C exert a more complex effect on thermostability. Crystal structures are determined to validate two rationally designed GPΔmuc trimers in their unliganded state. We then display a modified GPΔmuc trimer on reengineered protein nanoparticles that encapsulate a layer of locking domains (LD) and a cluster of helper T-cell epitopes. In mice and rabbits, GP trimers and nanoparticles elicit cross-ebolavirus NAbs, as well as non-NAbs that enhance pseudovirus infection. Repertoire sequencing reveals quantitative profiles of vaccine-induced B-cell responses. This study demonstrates a promising vaccine strategy for filoviruses, such as EBOV, based on GP stabilization and nanoparticle display.

Suggested Citation

  • Linling He & Anshul Chaudhary & Xiaohe Lin & Cindy Sou & Tanwee Alkutkar & Sonu Kumar & Timothy Ngo & Ezra Kosviner & Gabriel Ozorowski & Robyn L. Stanfield & Andrew B. Ward & Ian A. Wilson & Jiang Zh, 2021. "Single-component multilayered self-assembling nanoparticles presenting rationally designed glycoprotein trimers as Ebola virus vaccines," Nature Communications, Nature, vol. 12(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-22867-w
    DOI: 10.1038/s41467-021-22867-w
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    Cited by:

    1. Yi-Nan Zhang & Jennifer Paynter & Aleksandar Antanasijevic & Joel D. Allen & Mor Eldad & Yi-Zong Lee & Jeffrey Copps & Maddy L. Newby & Linling He & Deborah Chavez & Pat Frost & Anna Goodroe & John Du, 2023. "Single-component multilayered self-assembling protein nanoparticles presenting glycan-trimmed uncleaved prefusion optimized envelope trimers as HIV-1 vaccine candidates," Nature Communications, Nature, vol. 14(1), pages 1-29, December.

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