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

First Author  Wamhoff EC Year  2024
Journal  Nat Commun Volume  15
Issue  1 Pages  795
PubMed ID  38291019 Mgi Jnum  J:349967
Mgi Id  MGI:7580039 Doi  10.1038/s41467-024-44869-0
Citation  Wamhoff EC, et al. (2024) Enhancing antibody responses by multivalent antigen display on thymus-independent DNA origami scaffolds. Nat Commun 15(1):795
abstractText  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.
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