{"title":"在小鼠模型中用于免疫激活和动脉粥样硬化预防性保护的纳米疫苗","authors":"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, Dongping Sun","doi":"10.1038/s41467-025-57467-5","DOIUrl":null,"url":null,"abstract":"<p>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<sup>+</sup> effector/effector memory T cell responses. This nanovaccine modulates the DCs in the draining lymph nodes, activates both CD4<sup>+</sup> and CD8<sup>+</sup> 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<sup>−/−</sup> mice. Our nanovaccine design and preclinical data thus presents a potential candidate for prophylactic treatment for atherosclerosis.</p>","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"35 1","pages":""},"PeriodicalIF":15.7000,"publicationDate":"2025-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"A nanovaccine for immune activation and prophylactic protection of atherosclerosis in mouse models\",\"authors\":\"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, Dongping Sun\",\"doi\":\"10.1038/s41467-025-57467-5\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p>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<sup>+</sup> effector/effector memory T cell responses. This nanovaccine modulates the DCs in the draining lymph nodes, activates both CD4<sup>+</sup> and CD8<sup>+</sup> 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<sup>−/−</sup> mice. Our nanovaccine design and preclinical data thus presents a potential candidate for prophylactic treatment for atherosclerosis.</p>\",\"PeriodicalId\":19066,\"journal\":{\"name\":\"Nature Communications\",\"volume\":\"35 1\",\"pages\":\"\"},\"PeriodicalIF\":15.7000,\"publicationDate\":\"2025-03-02\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Nature Communications\",\"FirstCategoryId\":\"103\",\"ListUrlMain\":\"https://doi.org/10.1038/s41467-025-57467-5\",\"RegionNum\":1,\"RegionCategory\":\"综合性期刊\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"MULTIDISCIPLINARY SCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nature Communications","FirstCategoryId":"103","ListUrlMain":"https://doi.org/10.1038/s41467-025-57467-5","RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MULTIDISCIPLINARY SCIENCES","Score":null,"Total":0}
引用次数: 0
摘要
疫苗通过激发效应 T 细胞和抗体反应来预防动脉粥样硬化,而这需要有效传递抗原和佐剂以激活树突状细胞(DC)。在这里,我们展示了将抗原 p210 和佐剂 CpG 寡聚脱氧核苷酸单独缀合到超顺磁性氧化铁纳米粒子上形成的纳米疫苗鸡尾酒,它能激活 DCs 进行抗原交叉呈递,诱导共刺激信号、细胞因子和 CD8+效应/效应记忆 T 细胞反应。这种纳米疫苗能调节引流淋巴结中的 DC,激活 CD4+ 和 CD8+ T 细胞,诱导记忆反应,并诱导抗 p210 IgM 和 IgG 抗体,从而抑制动脉粥样硬化。最后,皮内接种三次这种纳米疫苗可减轻载脂蛋白E-/-小鼠动脉粥样硬化的发展。因此,我们的纳米疫苗设计和临床前数据为动脉粥样硬化的预防性治疗提供了一个潜在的候选方案。
A nanovaccine for immune activation and prophylactic protection of atherosclerosis in mouse models
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.
期刊介绍:
Nature Communications, an open-access journal, publishes high-quality research spanning all areas of the natural sciences. Papers featured in the journal showcase significant advances relevant to specialists in each respective field. With a 2-year impact factor of 16.6 (2022) and a median time of 8 days from submission to the first editorial decision, Nature Communications is committed to rapid dissemination of research findings. As a multidisciplinary journal, it welcomes contributions from biological, health, physical, chemical, Earth, social, mathematical, applied, and engineering sciences, aiming to highlight important breakthroughs within each domain.