Enhancing antibody responses by multivalent antigen display on thymus-independent DNA origami scaffolds
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s41467-024-44869-0.pdf
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1.77 MB
Format
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Checksum (MD5)
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Author(s)
Wamhoff, Eike-Christian
Ronsard, Larance
Feldman, Jared
Knappe, Grant A.
Hauser, Blake M.
Romanov, Anna
Case, James Brett
Sanapala, Shilpa
Lam, Evan C.
Denis, Kerri J. St.
Date Issued
January 30, 2024
Journal
Nature Communications
Publisher
Springer Science and Business Media LLC
Citation
Wamhoff, EC., Ronsard, L., Feldman, J. et al. Enhancing antibody responses by multivalent antigen display on thymus-independent DNA origami scaffolds. Nat Commun 15, 795 (2024).
Version
Final published version
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.
Subjects
General Physics and Astronomy
General Biochemistry, Genetics and Molecular Biology
General Chemistry
Multidisciplinary
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
Ragon Institute of MGH, MIT and Harvard
Massachusetts Institute of Technology. Department of Chemical Engineering
Koch Institute for Integrative Cancer Research at MIT
Terms of Use
Creative Commons Attribution
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DOI of Published Version
https://doi.org/10.1038/s41467-024-44869-0
