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Induction of tier-2 neutralizing antibodies in mice with a DNA-encoded HIV envelope native like trimer

Author

Listed:
  • Ziyang Xu

    (The Wistar Institute
    University of Pennsylvania)

  • Susanne Walker

    (The Wistar Institute)

  • Megan C. Wise

    (Inovio Pharmaceuticals)

  • Neethu Chokkalingam

    (The Wistar Institute)

  • Mansi Purwar

    (The Wistar Institute)

  • Alan Moore

    (Indiana University)

  • Edgar Tello-Ruiz

    (The Wistar Institute)

  • Yuanhan Wu

    (The Wistar Institute)

  • Sonali Majumdar

    (The Wistar Institute)

  • Kylie M. Konrath

    (The Wistar Institute
    University of Pennsylvania)

  • Abhijeet Kulkarni

    (The Wistar Institute)

  • Nicholas J. Tursi

    (The Wistar Institute
    University of Pennsylvania)

  • Faraz I. Zaidi

    (The Wistar Institute)

  • Emma L. Reuschel

    (The Wistar Institute)

  • Ishaan Patel

    (The Wistar Institute)

  • April Obeirne

    (The Wistar Institute)

  • Jianqiu Du

    (Indiana University)

  • Katherine Schultheis

    (Inovio Pharmaceuticals)

  • Lauren Gites

    (Inovio Pharmaceuticals)

  • Trevor Smith

    (Inovio Pharmaceuticals)

  • Janess Mendoza

    (Inovio Pharmaceuticals)

  • Kate E. Broderick

    (Inovio Pharmaceuticals)

  • Laurent Humeau

    (Inovio Pharmaceuticals)

  • Jesper Pallesen

    (Indiana University)

  • David B. Weiner

    (The Wistar Institute)

  • Daniel W. Kulp

    (The Wistar Institute)

Abstract

HIV Envelope (Env) is the main vaccine target for induction of neutralizing antibodies. Stabilizing Env into native-like trimer (NLT) conformations is required for recombinant protein immunogens to induce autologous neutralizing antibodies(nAbs) against difficult to neutralize HIV strains (tier-2) in rabbits and non-human primates. Immunizations of mice with NLTs have generally failed to induce tier-2 nAbs. Here, we show that DNA-encoded NLTs fold properly in vivo and induce autologous tier-2 nAbs in mice. DNA-encoded NLTs also uniquely induce both CD4 + and CD8 + T-cell responses as compared to corresponding protein immunizations. Murine neutralizing antibodies are identified with an advanced sequencing technology. The structure of an Env-Ab (C05) complex, as determined by cryo-EM, identifies a previously undescribed neutralizing Env C3/V5 epitope. Beyond potential functional immunity gains, DNA vaccines permit in vivo folding of structured antigens and provide significant cost and speed advantages for enabling rapid evaluation of new HIV vaccines.

Suggested Citation

  • 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.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-28363-z
    DOI: 10.1038/s41467-022-28363-z
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    References listed on IDEAS

    as
    1. Dan H. Barouch, 2008. "Challenges in the development of an HIV-1 vaccine," Nature, Nature, vol. 455(7213), pages 613-619, October.
    2. Catarina E Hioe & Terri Wrin & Michael S Seaman & Xuesong Yu & Blake Wood & Steve Self & Constance Williams & Miroslaw K Gorny & Susan Zolla-Pazner, 2010. "Anti-V3 Monoclonal Antibodies Display Broad Neutralizing Activities against Multiple HIV-1 Subtypes," PLOS ONE, Public Library of Science, vol. 5(4), pages 1-14, April.
    3. 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.
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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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