DNA origami vaccines program antigen-focused germinal centers
- Anna Romanov
- Grant A. Knappe
- Larance Ronsard
- Christopher A. Cottrell
- Yiming J. Zhang
- Heikyung Suh
- Lauren Duhamel
- Marjan Omer
- Asheley P. Chapman
- Katie Spivakovsky
- Patrick Skog
- Claudia T. Flynn
- Jeong Hyun Lee
- Oleksandr Kalyuzhniy
- Alessia Liguori
- Molly F. Parsons
- Vanessa R. Lewis
- Josue Canales
- Boris Reizis
- Ryan D. Tingle
- Torben Schiffner
- William R. Schief
- Daniel Lingwood
- Mark Bathe
- Darrell J. Irvine
2026-02-05
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.