该研究组合理设计了基于DNA折纸的病毒样颗粒（DNA-VLPs），显示了一种针对生殖系的HIV包膜蛋白免疫原，该颗粒没有引起支架特异性抗体反应。与最新的临床蛋白纳米颗粒相比，这些DNA-VLPs增加了表位特异性GC B细胞相对于脱靶B细胞的扩增，并且在CD4结合位点启动的人源化小鼠模型中增强了bnAb-系B细胞的扩增。它们最大限度地减少脱靶反应，增强了bnAb的启动，表明DNA-VLPs是一个有前途的疫苗平台。
据悉，在生发中心（GCs）中启动罕见的亚显性前体B细胞是疫苗接种产生广泛中和抗体（bnAbs）的中心目标。在蛋白质纳米颗粒支架上展示多价免疫原可以促进这种反应，但它也会产生支架特异性B细胞，理论上可以限制bnAb前体在GCs中的扩增。
附：英文原文
Title: DNA origami vaccines program antigen-focused germinal centers
Author: 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
Issue&Volume: 2026-02-05
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.
DOI: adx6291
Source: https://www.science.org/doi/10.1126/science.adx6291