Rationally designed multimeric nanovaccines using icosahedral DNA origami for display of SARS-CoV-2 receptor binding domain

Qingqing Feng, Keman Cheng, Lizhuo Zhang, Dongshu Wang, Xiaoyu Gao, Jie Liang, Guangna Liu, Nana Ma, Chen Xu, Ming Tang, Liting Chen, Xinwei Wang, Xuehui Ma, Jiajia Zou, Quanwei Shi, Pei Du, Qihui Wang, Hengliang Wang (), Guangjun Nie () and Xiao Zhao ()
Additional contact information
Qingqing Feng: National Center for Nanoscience and Technology of China
Keman Cheng: National Center for Nanoscience and Technology of China
Lizhuo Zhang: National Center for Nanoscience and Technology of China
Dongshu Wang: Beijing Institute of Biotechnology
Xiaoyu Gao: National Center for Nanoscience and Technology of China
Jie Liang: National Center for Nanoscience and Technology of China
Guangna Liu: National Center for Nanoscience and Technology of China
Nana Ma: National Center for Nanoscience and Technology of China
Chen Xu: National Center for Nanoscience and Technology of China
Ming Tang: National Center for Nanoscience and Technology of China
Liting Chen: National Center for Nanoscience and Technology of China
Xinwei Wang: National Center for Nanoscience and Technology of China
Xuehui Ma: Chinese Academy of Sciences
Jiajia Zou: Haidian District
Quanwei Shi: Haidian District
Pei Du: Chinese Academy of Sciences
Qihui Wang: Chinese Academy of Sciences
Hengliang Wang: Beijing Institute of Biotechnology
Guangjun Nie: National Center for Nanoscience and Technology of China
Xiao Zhao: National Center for Nanoscience and Technology of China

Nature Communications, 2024, vol. 15, issue 1, 1-17

Abstract: Abstract Multivalent antigen display on nanoparticles can enhance the immunogenicity of nanovaccines targeting viral moieties, such as the receptor binding domain (RBD) of SARS-CoV-2. However, particle morphology and size of current nanovaccines are significantly different from those of SARS-CoV-2. Additionally, surface antigen patterns are not controllable to enable the optimization of B cell activation. Herein, we employ an icosahedral DNA origami (ICO) as a display particle for RBD nanovaccines, achieving morphology and diameter like the virus (91 ± 11 nm). The surface addressability of DNA origami permits facile modification of the ICO surface with numerous RBD antigen clusters (ICO-RBD) to form various antigen patterns. Using an in vitro screening system, we demonstrate that the antigen spacing, antigen copies within clusters and cluster number parameters of the surface antigen pattern all impact the ability of the nanovaccines to activate B cells. Importantly, the optimized ICO-RBD nanovaccines evoke stronger and more enduring humoral and T cell immune responses in female mouse models compared to soluble RBD antigens, and the multivalent display broaden the protection range of B cell responses to more mutant strains. Our vaccines activate similar humoral immunity, observable stronger cellular immunity and more memory immune cells compared to trimeric mRNA vaccines.

Date: 2024
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DOI: 10.1038/s41467-024-53937-4

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