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Rationally designed multimeric nanovaccines using icosahedral DNA origami for display of SARS-CoV-2 receptor binding domain

Author

Listed:
  • Qingqing Feng

    (National Center for Nanoscience and Technology of China
    University of Chinese Academy of Sciences
    Chinese Academy of Sciences)

  • Keman Cheng

    (National Center for Nanoscience and Technology of China
    University of Chinese Academy of Sciences
    Chinese Academy of Sciences)

  • Lizhuo Zhang

    (National Center for Nanoscience and Technology of China
    University of Chinese Academy of Sciences
    Chinese Academy of Sciences)

  • Dongshu Wang

    (Beijing Institute of Biotechnology)

  • Xiaoyu Gao

    (National Center for Nanoscience and Technology of China
    University of Chinese Academy of Sciences
    Chinese Academy of Sciences)

  • Jie Liang

    (National Center for Nanoscience and Technology of China
    University of Chinese Academy of Sciences
    Chinese Academy of Sciences)

  • Guangna Liu

    (National Center for Nanoscience and Technology of China
    University of Chinese Academy of Sciences
    Chinese Academy of Sciences)

  • Nana Ma

    (National Center for Nanoscience and Technology of China
    University of Chinese Academy of Sciences
    Chinese Academy of Sciences)

  • Chen Xu

    (National Center for Nanoscience and Technology of China
    University of Chinese Academy of Sciences
    Chinese Academy of Sciences)

  • Ming Tang

    (National Center for Nanoscience and Technology of China
    University of Chinese Academy of Sciences
    Chinese Academy of Sciences)

  • Liting Chen

    (National Center for Nanoscience and Technology of China
    University of Chinese Academy of Sciences
    Chinese Academy of Sciences)

  • Xinwei Wang

    (National Center for Nanoscience and Technology of China
    University of Chinese Academy of Sciences
    Chinese Academy of Sciences)

  • Xuehui Ma

    (Chinese Academy of Sciences)

  • Jiajia Zou

    (Haidian District)

  • Quanwei Shi

    (Haidian District)

  • Pei Du

    (Chinese Academy of Sciences)

  • Qihui Wang

    (Chinese Academy of Sciences)

  • Hengliang Wang

    (Beijing Institute of Biotechnology)

  • Guangjun Nie

    (National Center for Nanoscience and Technology of China
    University of Chinese Academy of Sciences)

  • Xiao Zhao

    (National Center for Nanoscience and Technology of China
    University of Chinese Academy of Sciences
    Chinese Academy of Sciences)

Abstract

Multivalent antigen display on nanoparticles can enhance the immunogenicity of nanovaccines targeting viral moieties, such as the receptor binding domain (RBD) of SARS-CoV-2. However, particle morphology and size of current nanovaccines are significantly different from those of SARS-CoV-2. Additionally, surface antigen patterns are not controllable to enable the optimization of B cell activation. Herein, we employ an icosahedral DNA origami (ICO) as a display particle for RBD nanovaccines, achieving morphology and diameter like the virus (91 ± 11 nm). The surface addressability of DNA origami permits facile modification of the ICO surface with numerous RBD antigen clusters (ICO-RBD) to form various antigen patterns. Using an in vitro screening system, we demonstrate that the antigen spacing, antigen copies within clusters and cluster number parameters of the surface antigen pattern all impact the ability of the nanovaccines to activate B cells. Importantly, the optimized ICO-RBD nanovaccines evoke stronger and more enduring humoral and T cell immune responses in female mouse models compared to soluble RBD antigens, and the multivalent display broaden the protection range of B cell responses to more mutant strains. Our vaccines activate similar humoral immunity, observable stronger cellular immunity and more memory immune cells compared to trimeric mRNA vaccines.

Suggested Citation

  • Qingqing Feng & Keman Cheng & Lizhuo Zhang & Dongshu Wang & Xiaoyu Gao & Jie Liang & Guangna Liu & Nana Ma & Chen Xu & Ming Tang & Liting Chen & Xinwei Wang & Xuehui Ma & Jiajia Zou & Quanwei Shi & Pe, 2024. "Rationally designed multimeric nanovaccines using icosahedral DNA origami for display of SARS-CoV-2 receptor binding domain," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-53937-4
    DOI: 10.1038/s41467-024-53937-4
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