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Enhancing antibody responses by multivalent antigen display on thymus-independent DNA origami scaffolds

Author

Listed:
  • Eike-Christian Wamhoff

    (Massachusetts Institute of Technology)

  • Larance Ronsard

    (Massachusetts Institute of Technology and Harvard University)

  • Jared Feldman

    (Massachusetts Institute of Technology and Harvard University)

  • Grant A. Knappe

    (Massachusetts Institute of Technology
    Massachusetts Institute of Technology)

  • Blake M. Hauser

    (Massachusetts Institute of Technology and Harvard University)

  • Anna Romanov

    (Massachusetts Institute of Technology
    Massachusetts Institute of Technology)

  • James Brett Case

    (Washington University School of Medicine)

  • Shilpa Sanapala

    (Washington University School of Medicine)

  • Evan C. Lam

    (Massachusetts Institute of Technology and Harvard University)

  • Kerri J. St. Denis

    (Massachusetts Institute of Technology and Harvard University)

  • Julie Boucau

    (Massachusetts Institute of Technology and Harvard University)

  • Amy K. Barczak

    (Massachusetts Institute of Technology and Harvard University)

  • Alejandro B. Balazs

    (Massachusetts Institute of Technology and Harvard University)

  • Michael S. Diamond

    (Washington University School of Medicine
    Washington University School of Medicine
    Washington University School of Medicine)

  • Aaron G. Schmidt

    (Massachusetts Institute of Technology and Harvard University
    Harvard Medical School)

  • Daniel Lingwood

    (Massachusetts Institute of Technology and Harvard University)

  • Mark Bathe

    (Massachusetts Institute of Technology
    Broad Institute of MIT and Harvard
    Harvard Medical School)

Abstract

Protein-based virus-like particles (P-VLPs) are commonly used to spatially organize antigens and enhance humoral immunity through multivalent antigen display. However, P-VLPs are thymus-dependent antigens that are themselves immunogenic and can induce B cell responses that may neutralize the platform. Here, we investigate thymus-independent DNA origami as an alternative material for multivalent antigen display using the receptor binding domain (RBD) of the SARS-CoV-2 spike protein, the primary target of neutralizing antibody responses. Sequential immunization of mice with DNA-based VLPs (DNA-VLPs) elicits protective neutralizing antibodies to SARS-CoV-2 in a manner that depends on the valency of the antigen displayed and on T cell help. Importantly, the immune sera do not contain boosted, class-switched antibodies against the DNA scaffold, in contrast to P-VLPs that elicit strong B cell memory against both the target antigen and the scaffold. Thus, DNA-VLPs enhance target antigen immunogenicity without generating scaffold-directed immunity and thereby offer an important alternative material for particulate vaccine design.

Suggested Citation

  • Eike-Christian Wamhoff & Larance Ronsard & Jared Feldman & Grant A. Knappe & Blake M. Hauser & Anna Romanov & James Brett Case & Shilpa Sanapala & Evan C. Lam & Kerri J. St. Denis & Julie Boucau & Amy, 2024. "Enhancing antibody responses by multivalent antigen display on thymus-independent DNA origami scaffolds," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-44869-0
    DOI: 10.1038/s41467-024-44869-0
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    References listed on IDEAS

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    1. 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.

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