DNA origami vaccines program antigen-focused germinal centers

Multivalent immunogen display on protein nanoparticles is a well-established method to promote such responses. However, these nanoparticles generate scaffold-specific B cells that could theoretically limit bnAb precursor expansion in GCs.

We rationally designed DNA origami-based virus-like particles (VLPs) displaying a germline-targeting HIV Env immunogen, which elicited no scaffold-specific antibody responses and increased the expansion of epitope-specific GC B cells relative to off-target B cells >10-fold compared with a state-of-the-art clinical protein nanoparticle, which failed to expand bnAb precursors in these conditions. Our results demonstrate that minimizing off-target responses enhances bnAb priming and support DNA-VLPs as a potent vaccine platform.