DNA origami vaccines program antigen-focused germinal centers.
| Authors | |
| 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. |
| Year of Publication | 2026
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| Journal | Science (New York, N.Y.)
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| Volume | 391
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| Issue | 6785
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| Pages | eadx6291
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| Date Published | 02/2026
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| ISSN | 1095-9203
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| DOI | 10.1126/science.adx6291
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| PubMed ID | 41643005
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