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Single-component multilayered self-assembling protein nanoparticles presenting glycan-trimmed uncleaved prefusion optimized envelope trimers as HIV-1 vaccine candidates

Author

Listed:
  • Yi-Nan Zhang

    (The Scripps Research Institute)

  • Jennifer Paynter

    (The Scripps Research Institute)

  • Aleksandar Antanasijevic

    (The Scripps Research Institute
    The Scripps Research Institute)

  • Joel D. Allen

    (University of Southampton)

  • Mor Eldad

    (The Scripps Research Institute)

  • Yi-Zong Lee

    (The Scripps Research Institute)

  • Jeffrey Copps

    (The Scripps Research Institute
    The Scripps Research Institute)

  • Maddy L. Newby

    (University of Southampton)

  • Linling He

    (The Scripps Research Institute)

  • Deborah Chavez

    (Texas Biomedical Research Institute)

  • Pat Frost

    (Texas Biomedical Research Institute)

  • Anna Goodroe

    (Texas Biomedical Research Institute)

  • John Dutton

    (Texas Biomedical Research Institute)

  • Robert Lanford

    (Texas Biomedical Research Institute)

  • Christopher Chen

    (Texas Biomedical Research Institute)

  • Ian A. Wilson

    (The Scripps Research Institute
    The Scripps Research Institute
    The Scripps Research Institute)

  • Max Crispin

    (University of Southampton)

  • Andrew B. Ward

    (The Scripps Research Institute
    The Scripps Research Institute)

  • Jiang Zhu

    (The Scripps Research Institute
    The Scripps Research Institute)

Abstract

Uncleaved prefusion-optimized (UFO) design can stabilize diverse HIV-1 envelope glycoproteins (Envs). Single-component, self-assembling protein nanoparticles (1c-SApNP) can display 8 or 20 native-like Env trimers as vaccine candidates. We characterize the biophysical, structural, and antigenic properties of 1c-SApNPs that present the BG505 UFO trimer with wildtype and modified glycans. For 1c-SApNPs, glycan trimming improves recognition of the CD4 binding site without affecting broadly neutralizing antibodies (bNAbs) to major glycan epitopes. In mice, rabbits, and nonhuman primates, glycan trimming increases the frequency of vaccine responders (FVR) and steers antibody responses away from immunodominant glycan holes and glycan patches. The mechanism of vaccine-induced immunity is examined in mice. Compared with the UFO trimer, the multilayered E2p and I3-01v9 1c-SApNPs show 420 times longer retention in lymph node follicles, 20-32 times greater presentation on follicular dendritic cell dendrites, and up-to-4 times stronger germinal center reactions. These findings can inform future HIV-1 vaccine development.

Suggested Citation

  • 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.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-37742-z
    DOI: 10.1038/s41467-023-37742-z
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    as
    1. Ziyang Xu & Susanne Walker & Megan C. Wise & Neethu Chokkalingam & Mansi Purwar & Alan Moore & Edgar Tello-Ruiz & Yuanhan Wu & Sonali Majumdar & Kylie M. Konrath & Abhijeet Kulkarni & Nicholas J. Turs, 2022. "Induction of tier-2 neutralizing antibodies in mice with a DNA-encoded HIV envelope native like trimer," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    2. Yang Hsia & Jacob B. Bale & Shane Gonen & Dan Shi & William Sheffler & Kimberly K. Fong & Una Nattermann & Chunfu Xu & Po-Ssu Huang & Rashmi Ravichandran & Sue Yi & Trisha N. Davis & Tamir Gonen & Nei, 2016. "Design of a hyperstable 60-subunit protein icosahedron," Nature, Nature, vol. 535(7610), pages 136-139, July.
    3. Leopold Kong & Linling He & Natalia de Val & Nemil Vora & Charles D. Morris & Parisa Azadnia & Devin Sok & Bin Zhou & Dennis R. Burton & Andrew B. Ward & Ian A. Wilson & Jiang Zhu, 2016. "Uncleaved prefusion-optimized gp140 trimers derived from analysis of HIV-1 envelope metastability," Nature Communications, Nature, vol. 7(1), pages 1-15, November.
    4. Christopher N. Scanlan & John Offer & Nicole Zitzmann & Raymond A. Dwek, 2007. "Exploiting the defensive sugars of HIV-1 for drug and vaccine design," Nature, Nature, vol. 446(7139), pages 1038-1045, April.
    5. Aleksandar Antanasijevic & Leigh M. Sewall & Christopher A. Cottrell & Diane G. Carnathan & Luis E. Jimenez & Julia T. Ngo & Jennifer B. Silverman & Bettina Groschel & Erik Georgeson & Jinal Bhiman & , 2021. "Polyclonal antibody responses to HIV Env immunogens resolved using cryoEM," Nature Communications, Nature, vol. 12(1), pages 1-17, December.
    6. Liwei Cao & Matthias Pauthner & Raiees Andrabi & Kimmo Rantalainen & Zachary Berndsen & Jolene K. Diedrich & Sergey Menis & Devin Sok & Raiza Bastidas & Sung-Kyu Robin Park & Claire M. Delahunty & Lin, 2018. "Differential processing of HIV envelope glycans on the virus and soluble recombinant trimer," Nature Communications, Nature, vol. 9(1), pages 1-14, December.
    7. 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.
    8. Daniel W. Kulp & Jon M. Steichen & Matthias Pauthner & Xiaozhen Hu & Torben Schiffner & Alessia Liguori & Christopher A. Cottrell & Colin Havenar-Daughton & Gabriel Ozorowski & Erik Georgeson & Oleksa, 2017. "Structure-based design of native-like HIV-1 envelope trimers to silence non-neutralizing epitopes and eliminate CD4 binding," Nature Communications, Nature, vol. 8(1), pages 1-14, December.
    9. Serban L. Ilca & Abhay Kotecha & Xiaoyu Sun & Minna M. Poranen & David I. Stuart & Juha T. Huiskonen, 2015. "Localized reconstruction of subunits from electron cryomicroscopy images of macromolecular complexes," Nature Communications, Nature, vol. 6(1), pages 1-8, December.
    10. Rory Henderson & Maolin Lu & Ye Zhou & Zekun Mu & Robert Parks & Qifeng Han & Allen L. Hsu & Elizabeth Carter & Scott C. Blanchard & R J Edwards & Kevin Wiehe & Kevin O. Saunders & Mario J. Borgnia & , 2020. "Disruption of the HIV-1 Envelope allosteric network blocks CD4-induced rearrangements," Nature Communications, Nature, vol. 11(1), pages 1-14, December.
    11. Kwinten Sliepen & Byung Woo Han & Ilja Bontjer & Petra Mooij & Fernando Garces & Anna-Janina Behrens & Kimmo Rantalainen & Sonu Kumar & Anita Sarkar & Philip J. M. Brouwer & Yuanzi Hua & Monica Tolazz, 2019. "Structure and immunogenicity of a stabilized HIV-1 envelope trimer based on a group-M consensus sequence," Nature Communications, Nature, vol. 10(1), pages 1-16, December.
    12. Jinghe Huang & Byong H. Kang & Marie Pancera & Jeong Hyun Lee & Tommy Tong & Yu Feng & Hiromi Imamichi & Ivelin S. Georgiev & Gwo-Yu Chuang & Aliaksandr Druz & Nicole A. Doria-Rose & Leo Laub & Kwinte, 2014. "Broad and potent HIV-1 neutralization by a human antibody that binds the gp41–gp120 interface," Nature, Nature, vol. 515(7525), pages 138-142, November.
    13. Xiping Wei & Julie M. Decker & Shuyi Wang & Huxiong Hui & John C. Kappes & Xiaoyun Wu & Jesus F. Salazar-Gonzalez & Maria G. Salazar & J. Michael Kilby & Michael S. Saag & Natalia L. Komarova & Martin, 2003. "Antibody neutralization and escape by HIV-1," Nature, Nature, vol. 422(6929), pages 307-312, March.
    14. 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.
    15. Marie Pancera & Tongqing Zhou & Aliaksandr Druz & Ivelin S. Georgiev & Cinque Soto & Jason Gorman & Jinghe Huang & Priyamvada Acharya & Gwo-Yu Chuang & Gilad Ofek & Guillaume B. E. Stewart-Jones & Jon, 2014. "Structure and immune recognition of trimeric pre-fusion HIV-1 Env," Nature, Nature, vol. 514(7523), pages 455-461, October.
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