DNA origami vaccines program antigen-focused germinal centers.

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Tác giả: Mark Bathe, Josue Canales, Asheley P Chapman, Christopher A Cottrell, Darrell J Irvine, Grant A Knappe, Vanessa R Lewis, Daniel Lingwood, Marjan Omer, Boris Reizis, Anna Romanov, Larance Ronsard, Torben Schiffner, Katie Spivakovsky, Heikyung Suh, Ryan D Tingle

Ngôn ngữ: eng

Ký hiệu phân loại: 621.384196 Electrical, magnetic, optical, communications, computer engineering; electronics, lighting

Thông tin xuất bản: United States : bioRxiv : the preprint server for biology , 2025

Mô tả vật lý:

Bộ sưu tập: NCBI

ID: 682777

Recruitment and expansion of rare precursor B cells in germinal centers (GCs) is a central goal of vaccination to generate broadly neutralizing antibodies (bnAbs) against challenging pathogens such as HIV. Multivalent immunogen display is a well-established method to enhance vaccine-induced B cell responses, typically accomplished by using natural or engineered protein scaffolds. However, these scaffolds themselves are targets of antibody responses, with the potential to generate competitor scaffold-specific B cells that could theoretically limit expansion and maturation of "on-target" B cells in the GC response. Here, we rationally designed T-independent, DNA-origami based virus-like particles (VLPs) with optimal antigenic display of the germline targeting HIV Env immunogen, eOD-GT8, and appropriate T cell help to achieve a potent GC response. In preclinical mouse models, these DNA-VLPs expanded significantly higher frequencies of epitope-specific GC B cells compared with a state-of-the-art clinical protein nanoparticle. Optimized DNA-VLPs primed germinal centers focused on the target antigen and rapidly expanded subdominant broadly neutralizing antibody precursor B cells for HIV with a single immunization. Thus, avoiding scaffold-specific responses augments priming of bnAb precursor B cells, and DNA-VLPs are a promising platform for promoting B cell responses towards challenging subdominant epitopes.
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