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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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