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Natural Sciences›Chemistry›molecular-biology, cell-biology

DNA origami vaccines program antigen-focused germinal centers

Anna RomanovMassachusetts Institute of Technology

Grant A. KnappeMassachusetts Institute of Technology

Larance RonsardRagon Institute of MGH, MIT and Harvard

Christopher A. CottrellScripps Research Institute

Yiming J. ZhangMassachusetts Institute of Technology

Heikyung SuhScripps Research Institute

Lauren DuhamelMassachusetts Institute of Technology

Marjan OmerAarhus University

Asheley P. ChapmanScripps Research Institute

Katie SpivakovskyMassachusetts Institute of Technology

Science·February 5, 2026·1 citations

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Abstract

Priming rare subdominant precursor B cells in germinal centers (GCs) is a central goal of vaccination to generate broadly neutralizing antibodies (bnAbs) against HIV. Multivalent immunogen display on protein nanoparticle scaffolds can promote such responses, but it also generates scaffold-specific B cells that could theoretically limit bnAb precursor expansion in GCs. We rationally designed DNA origami–based virus-like particles (DNA-VLPs) displaying a germline-targeting HIV envelope protein immunogen, which elicited no scaffold-specific antibody responses. Compared with a state-of-the-art clinical protein nanoparticle, these DNA-VLPs increased the expansion of epitope-specific GC B cells relative to off-target B cells and enhanced expansion of bnAb-lineage B cells in a humanized mouse model of CD4 binding site priming. Thus, minimizing off-target responses enhances bnAb priming and indicates that DNA-VLPs are a promising vaccine platform.

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