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Presenting native-like trimeric HIV-1 antigens with self-assembling nanoparticles

Author

Listed:
  • Linling He

    (The Scripps Research Institute)

  • Natalia de Val

    (The Scripps Research Institute
    International AIDS Vaccine Initiative Neutralizing Antibody Center and the Collaboration for AIDS Vaccine Discovery, The Scripps Research Institute
    Scripps Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute)

  • Charles D. Morris

    (The Scripps Research Institute)

  • Nemil Vora

    (The Scripps Research Institute)

  • Therese C. Thinnes

    (The Scripps Research Institute)

  • Leopold Kong

    (The Scripps Research Institute
    International AIDS Vaccine Initiative Neutralizing Antibody Center and the Collaboration for AIDS Vaccine Discovery, The Scripps Research Institute
    Scripps Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute)

  • Parisa Azadnia

    (The Scripps Research Institute)

  • Devin Sok

    (The Scripps Research Institute
    International AIDS Vaccine Initiative Neutralizing Antibody Center and the Collaboration for AIDS Vaccine Discovery, The Scripps Research Institute
    Scripps Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute)

  • Bin Zhou

    (The Scripps Research Institute)

  • Dennis R. Burton

    (The Scripps Research Institute
    International AIDS Vaccine Initiative Neutralizing Antibody Center and the Collaboration for AIDS Vaccine Discovery, The Scripps Research Institute
    Scripps Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute
    Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard)

  • Ian A Wilson

    (The Scripps Research Institute
    International AIDS Vaccine Initiative Neutralizing Antibody Center and the Collaboration for AIDS Vaccine Discovery, The Scripps Research Institute
    Scripps Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute
    The Joint Center for Structural Genomics, The Scripps Research Institute)

  • David Nemazee

    (The Scripps Research Institute)

  • Andrew B. Ward

    (The Scripps Research Institute
    International AIDS Vaccine Initiative Neutralizing Antibody Center and the Collaboration for AIDS Vaccine Discovery, The Scripps Research Institute
    Scripps Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute)

  • Jiang Zhu

    (The Scripps Research Institute
    The Scripps Research Institute
    Scripps Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute)

Abstract

Structures of BG505 SOSIP.664 trimer in complex with broadly neutralizing antibodies (bNAbs) have revealed the critical role of trimeric context for immune recognition of HIV-1. Presentation of trimeric HIV-1 antigens on nanoparticles may thus provide promising vaccine candidates. Here we report the rational design, structural analysis and antigenic evaluation of HIV-1 trimer-presenting nanoparticles. We first demonstrate that both V1V2 and gp120 can be presented in native-like trimeric conformations on nanoparticles. We then design nanoparticles presenting various forms of stabilized gp140 trimer based on ferritin and a large, 60-meric E2p that displays 20 spikes mimicking virus-like particles (VLPs). Particle assembly is confirmed by electron microscopy (EM), while antigenic profiles are generated using representative bNAbs and non-NAbs. Lastly, we demonstrate high-yield gp140 nanoparticle production and robust stimulation of B cells carrying cognate VRC01 receptors by gp120 and gp140 nanoparticles. Together, our study provides an arsenal of multivalent immunogens for HIV-1 vaccine development.

Suggested Citation

  • Linling He & Natalia de Val & Charles D. Morris & Nemil Vora & Therese C. Thinnes & Leopold Kong & Parisa Azadnia & Devin Sok & Bin Zhou & Dennis R. Burton & Ian A Wilson & David Nemazee & Andrew B. W, 2016. "Presenting native-like trimeric HIV-1 antigens with self-assembling nanoparticles," Nature Communications, Nature, vol. 7(1), pages 1-15, November.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms12041
    DOI: 10.1038/ncomms12041
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    Cited by:

    1. Dan Fu & Wenming Wang & Yan Zhang & Fan Zhang & Pinyi Yang & Chun Yang & Yufei Tian & Renqi Yao & Jingwu Jian & Zixian Sun & Nan Zhang & Zhiyu Ni & Zihe Rao & Lei Zhao & Yu Guo, 2024. "Self-assembling nanoparticle engineered from the ferritinophagy complex as a rabies virus vaccine candidate," Nature Communications, Nature, vol. 15(1), pages 1-21, December.
    2. Mallory L. Myers & John R. Gallagher & Alexander J. Kim & Walker H. Payne & Samantha Maldonado-Puga & Haralabos Assimakopoulos & Kevin W. Bock & Udana Torian & Ian N. Moore & Audray K. Harris, 2023. "Commercial influenza vaccines vary in HA-complex structure and in induction of cross-reactive HA antibodies," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    3. 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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