Rationally designed multimeric nanovaccines using icosahedral DNA origami for display of SARS-CoV-2 receptor binding domain
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....
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Nature Portfolio
2024-11-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-53937-4 |
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| author | 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 Xiao Zhao |
| author_facet | 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 Xiao Zhao |
| author_sort | Qingqing Feng |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-9b40f8e17bd9471d9ab1c78853fbd73c |
| institution | DOAJ |
| issn | 2041-1723 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-9b40f8e17bd9471d9ab1c78853fbd73c2025-08-20T02:49:59ZengNature PortfolioNature Communications2041-17232024-11-0115111710.1038/s41467-024-53937-4Rationally designed multimeric nanovaccines using icosahedral DNA origami for display of SARS-CoV-2 receptor binding domainQingqing Feng0Keman Cheng1Lizhuo Zhang2Dongshu Wang3Xiaoyu Gao4Jie Liang5Guangna Liu6Nana Ma7Chen Xu8Ming Tang9Liting Chen10Xinwei Wang11Xuehui Ma12Jiajia Zou13Quanwei Shi14Pei Du15Qihui Wang16Hengliang Wang17Guangjun Nie18Xiao Zhao19CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety & CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of ChinaCAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety & CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of ChinaCAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety & CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of ChinaState Key Laboratory of Pathogens and Biosecurity, Laboratory of Advanced Biotechnology, Beijing Institute of BiotechnologyCAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety & CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of ChinaCAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety & CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of ChinaCAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety & CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of ChinaCAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety & CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of ChinaCAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety & CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of ChinaCAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety & CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of ChinaCAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety & CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of ChinaCAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety & CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of ChinaCAS Key Laboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Chinese Academy of SciencesBeijing Intell Nanomedicine, No. 9, Chengwan Street, Haidian DistrictBeijing Intell Nanomedicine, No. 9, Chengwan Street, Haidian DistrictCAS Key Laboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Chinese Academy of SciencesCAS Key Laboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Chinese Academy of SciencesState Key Laboratory of Pathogens and Biosecurity, Laboratory of Advanced Biotechnology, Beijing Institute of BiotechnologyCAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety & CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of ChinaCAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety & CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of ChinaAbstract 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.https://doi.org/10.1038/s41467-024-53937-4 |
| spellingShingle | 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 Xiao Zhao Rationally designed multimeric nanovaccines using icosahedral DNA origami for display of SARS-CoV-2 receptor binding domain Nature Communications |
| title | Rationally designed multimeric nanovaccines using icosahedral DNA origami for display of SARS-CoV-2 receptor binding domain |
| title_full | Rationally designed multimeric nanovaccines using icosahedral DNA origami for display of SARS-CoV-2 receptor binding domain |
| title_fullStr | Rationally designed multimeric nanovaccines using icosahedral DNA origami for display of SARS-CoV-2 receptor binding domain |
| title_full_unstemmed | Rationally designed multimeric nanovaccines using icosahedral DNA origami for display of SARS-CoV-2 receptor binding domain |
| title_short | Rationally designed multimeric nanovaccines using icosahedral DNA origami for display of SARS-CoV-2 receptor binding domain |
| title_sort | rationally designed multimeric nanovaccines using icosahedral dna origami for display of sars cov 2 receptor binding domain |
| url | https://doi.org/10.1038/s41467-024-53937-4 |
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