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Here, we investigated DNA origami as an alternative material for multivalent antigen display in vivo, applied to the receptor binding domain (RBD) of SARS-CoV-2 that is the primary antigenic target of neutralizing antibody responses. Icosahedral DNA-VLPs elicited neutralizing antibodies to SARS-CoV-2 in a valency-dependent manner following sequential immunization in mice, quantified by pseudo-and live-virus neutralization assays. Further, induction of B cell memory against the RBD required T cell help, but the immune sera did not contain boosted, class-switched antibodies against the DNA scaffold. This contrasted with protein-based VLP display of the RBD that elicited B cell memory against both the target antigen and the scaffold. Thus, DNA-based VLPs enhance target antigen immunogenicity without generating off-target, scaffold-directed immune memory, thereby offering a potentially important alternative material for particulate vaccine design.<\/jats:p>","DOI":"10.1101\/2022.08.16.504128","type":"posted-content","created":{"date-parts":[[2022,8,17]],"date-time":"2022-08-17T18:30:10Z","timestamp":1660761010000},"source":"Crossref","is-referenced-by-count":14,"title":["Enhancing antibody responses by multivalent antigen display on thymus-independent DNA origami scaffolds"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8665-5512","authenticated-orcid":false,"given":"Eike-Christian","family":"Wamhoff","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5307-1940","authenticated-orcid":false,"given":"Larance","family":"Ronsard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4387-9954","authenticated-orcid":false,"given":"Jared","family":"Feldman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5041-2383","authenticated-orcid":false,"given":"Grant A.","family":"Knappe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0100-1684","authenticated-orcid":false,"given":"Blake 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