A nanovaccine for immune activation and prophylactic protection of atherosclerosis in mouse models

Lei Zhang, Abdulrahman AL-Ammari, Danxuan Zhu, Hongsong Zhang, Peng Zhou, Xu Zhi, Weixiao Ding, Xinmeng Li, Qingqing Yu, Yuwen Gai, Xiaoling Ma, Chuntao Chen, Chao Zuo, Jiaan Zhang (), Wanying Zhu () and Dongping Sun ()
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Lei Zhang: Nanjing University of Science and Technology
Abdulrahman AL-Ammari: University of Science and Technology of China
Danxuan Zhu: The First Affiliated Hospital of Nanjing Medical University
Hongsong Zhang: Nanjing Medical University
Peng Zhou: Nanjing University of Science and Technology
Xu Zhi: Nanjing University
Weixiao Ding: Nanjing University of Science and Technology
Xinmeng Li: Nanjing University of Science and Technology
Qingqing Yu: Nanjing University of Science and Technology
Yuwen Gai: Nanjing University of Science and Technology
Xiaoling Ma: The First Affiliated Hospital of Nanjing Medical University
Chuntao Chen: Nanjing University of Science and Technology
Chao Zuo: Nanjing University of Science and Technology
Jiaan Zhang: Chinese Academy of Medical Sciences and Peking Union Medical College
Wanying Zhu: Nanjing Medical University
Dongping Sun: Nanjing University of Science and Technology

Nature Communications, 2025, vol. 16, issue 1, 1-19

Abstract: Abstract Vaccines offer prophylactic treatments against atherosclerosis by eliciting effector T cell and antibody responses, which require effective delivery of antigen and adjuvant to activate dendritic cells (DC). Here we show that individual conjugation of antigen p210 and adjuvant CpG oligodeoxynucleotides onto superparamagnetic iron oxide nanoparticles formulates a nanovaccine cocktail that activates DCs for antigen cross-presentation and induction of co-stimulatory signals, cytokines and CD8+ effector/effector memory T cell responses. This nanovaccine modulates the DCs in the draining lymph nodes, activates both CD4+ and CD8+ T cells, elicits memory responses, and induces both anti-p210 IgM and IgG antibodies to suppress atherosclerosis. Lastly, three intradermal vaccinations of this nanovaccine mitigate the atherosclerosis development in the ApoE−/− mice. Our nanovaccine design and preclinical data thus presents a potential candidate for prophylactic treatment for atherosclerosis.

Date: 2025
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DOI: 10.1038/s41467-025-57467-5

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