DNA origami vaccines program antigen-focused germinal centers

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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Publication Details

Journal
Science
Published
2026-02-05
DOI
https://doi.org/10.1126/science.adx6291
Citations
3
Primary Topic
Immunotherapy and Immune Responses
Type
article
Field-Weighted Citation Impact
73.30
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article

DNA origami vaccines program antigen-focused germinal centers

Boris Reizis, Anna Romanov, Molly F. Parsons, Jeong Hyun Lee et al.
3 citations
Science
Immunotherapy and Immune Responses
73.30
article

DNA origami vaccines program antigen-focused germinal centers

Boris Reizis, Anna Romanov, Molly F. Parsons, Jeong Hyun Lee, Ryan Tingle, DJ Irvine, Mark Bathe, Josue Canales, Heikyung Suh, Patrick Skog, Alessia Liguori, Marjan Omer, William R. Schief, Lauren Duhamel, Grant A. Knappe, Kalyuzhniy Oleksandr, Vanessa Lewis, Asheley P. Chapman, Katie Spivakovsky, Larance Ronsard, Claudia T. Flynn, Torben Schiffner, Christopher A. Cottrell, Yiming J. Zhang, Daniel Lingwood
article en
3 citations

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.

ScienceVol. 391(6785)
Broad Institute (US), Scripps Research Institute (US), International AIDS Vaccine Initiative (US), Howard Hughes Medical Institute (US), Harvard University (US), Aarhus University (DK), Ragon Institute of MGH, MIT and Harvard (US), Harvard Affiliated Emergency Medicine Residency (US), Moderna Therapeutics (United States) (US), New York University (US), Massachusetts Institute of Technology (US)
Good health and well-being
Openalex Percentile: Top 0%
Immunotherapy and Immune Responses
73.30
DOISourceOpenAlex
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