DNA‐Engineered Modular Nanovaccines Featuring Precise Topology for Enhanced Immunogenicity
Abstract
AbstractMultivalent display of antigens can boost subunit vaccine immunogenicity. However, owing to the inherent difficulty in programmatically controlling the topology of multivalent antigens, its impact on antigen immunogenicity remains elusive. In this study, DNA‐mediated modular precision assembly is employed to organize SARS‐CoV‐2 receptor‐binding domains (RBDs) with different topological connections while preserving their epitopes. It is found that branching‐connected RBDs induced significantly higher IgG titers than linear‐connected RBDs at higher antigen valency (≥4). This increase in IgG response is associated with stronger B cell proliferation, likely due to enhanced antigen‐receptor synergistic interactions leading to enhanced B cell receptor signaling. Branching‐connected RBDs also provided superior humoral immunity in mice and stronger protection in SARS‐CoV‐2‐infected hamsters compared to adjuvanted RBD. This work highlights the role of antigen topology in vaccine design and offers a universal modular platform for producing more effective subunit vaccines.
Article Details
Authors (14)
Yanfei Qu
Institute of Materiobiology Department of Chemistry College of Science Shanghai University Shanghai 200444 China
Dawei Wang
Lehn Institute of Functional Materials, GBRCE for Functional Molecular Engineering, IGCME, School of Chemistry
Yunlong Zhang
State Key Laboratory of Catalysis, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Zhongshan Road 457, Dalian 116023, China
Fengyun Shen
Institute of Materiobiology Department of Chemistry College of Science Shanghai University Shanghai 200444 China
Binghui Xia
Department of Microbiology Faculty of Naval Medicine Naval Medical University Shanghai 200433 China
Qin Xu
Qisheng Wang
Shanghai Advanced Research Institute, Chinese Academy of Sciences
Huating Kong
Shanghai Synchrotron Radiation Facility (SSRF) Shanghai Advanced Research Institute Chinese Academy of Sciences Shanghai 201204 China
Ying Zhu
Lihua Wang
Itamar Willner
Institute of Chemistry
Xiurong Yang
State Key Laboratory of Electroanalytical Chemistry Changchun Institute of Applied Chemistry Chinese Academy of Sciences Changchun Jilin China
Chunhai Fan
State Key Laboratory of Synergistic Chem-Bio Synthesis, School of Chemistry and Chemical Engineering, New Cornerstone Science Laboratory, Frontiers Science Center for Transformative Molecules, Zhang Jiang Institute for Advanced Study and National Center for Translational Medicine
Lele Sun
Institute of Materiobiology Department of Chemistry College of Science Shanghai University Shanghai 200444 China