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新型 ATR-AP205-001 结合型抗高血压疫苗的免疫反应。

Immune Response of A Novel ATR-AP205-001 Conjugate Anti-hypertensive Vaccine.

机构信息

Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.

Institute of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.

出版信息

Sci Rep. 2017 Oct 3;7(1):12580. doi: 10.1038/s41598-017-12996-y.

DOI:10.1038/s41598-017-12996-y
PMID:28974760
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5626684/
Abstract

We developed a virus-like particle (VLP)-based therapeutic vaccine against angiotensin II receptor type 1, ATR-AP205-001, which could significantly reduce the blood pressure and protect target organs of hypertensive animals. In this study, we focused on the immunological effect and safety of the VLP-based vaccine. By comparing to the depolymerized dimeric vaccine ATR-Dimer-001, we found that ATR-AP205-001 reached subcapsular sinus of lymph node shortly after administration, followed by accumulation on follicle dendritic cells via follicle B cell transportation, while ATR-Dimer-001 vaccine showed no association with FDCs. ATR-AP205-001 vaccine strongly activated dendritic cells, which promoted T cells differentiation to follicular helper T cells. ATR-AP205-001 vaccine induced powerful germinal center reaction, which was translated to a boost of specific antibody production and long-lasting B cell memory, far superior to ATR-Dimer-001 vaccine. Moreover, neither cytotoxic T cells, nor Th1/Th17 cell-mediated inflammation was observed in ATR-AP205-001 vaccine, similar to ATR-Dimer-001 vaccine. We concluded that ATR-AP205-001 vaccine quickly induced potent humoral immunity through collaboration of B cells, follicular dendritic cells and follicular helper T cells, providing an effective and safe intervention for hypertension in the future clinical application.

摘要

我们开发了一种基于病毒样颗粒（VLP）的血管紧张素 II 受体 1 型（ATR-AP205-001）治疗性疫苗，该疫苗可显著降低高血压动物的血压并保护靶器官。在这项研究中，我们专注于 VLP 疫苗的免疫效果和安全性。通过与解聚二聚体疫苗 ATR-Dimer-001 进行比较，我们发现 ATR-AP205-001 在给药后很快就到达淋巴结的被膜下窦，随后通过滤泡 B 细胞转运在滤泡树突状细胞上积累，而 ATR-Dimer-001 疫苗与 FDC 没有关联。ATR-AP205-001 疫苗强烈激活树突状细胞，促进 T 细胞分化为滤泡辅助 T 细胞。ATR-AP205-001 疫苗诱导了强烈的生发中心反应，这转化为特异性抗体产生的增强和持久的 B 细胞记忆，远远优于 ATR-Dimer-001 疫苗。此外，在 ATR-AP205-001 疫苗中未观察到细胞毒性 T 细胞或 Th1/Th17 细胞介导的炎症，与 ATR-Dimer-001 疫苗相似。我们得出结论，ATR-AP205-001 疫苗通过 B 细胞、滤泡树突状细胞和滤泡辅助 T 细胞的协作，迅速诱导强烈的体液免疫，为未来的高血压临床应用提供了一种有效和安全的干预措施。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/246f/5626684/72f7ce9b9a37/41598_2017_12996_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/246f/5626684/a95c16482bb4/41598_2017_12996_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/246f/5626684/c2035d541f4e/41598_2017_12996_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/246f/5626684/7514da9ed405/41598_2017_12996_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/246f/5626684/9bd8add2a18f/41598_2017_12996_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/246f/5626684/7e8de93d9d72/41598_2017_12996_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/246f/5626684/8d602eb3d60f/41598_2017_12996_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/246f/5626684/72f7ce9b9a37/41598_2017_12996_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/246f/5626684/a95c16482bb4/41598_2017_12996_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/246f/5626684/c2035d541f4e/41598_2017_12996_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/246f/5626684/7514da9ed405/41598_2017_12996_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/246f/5626684/9bd8add2a18f/41598_2017_12996_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/246f/5626684/7e8de93d9d72/41598_2017_12996_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/246f/5626684/8d602eb3d60f/41598_2017_12996_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/246f/5626684/72f7ce9b9a37/41598_2017_12996_Fig7_HTML.jpg

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Immune Response of A Novel ATR-AP205-001 Conjugate Anti-hypertensive Vaccine.

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本文引用的文献

[1]
Human CD8 T Cells Damage Noninfected Epithelial Cells during Influenza Virus Infection In Vitro.

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Nanoparticle conjugation enhances the immunomodulatory effects of intranasally delivered CpG in house dust mite-allergic mice.

Sci Rep. 2015-9-21

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Virology. 2014-1-10

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A systems approach to designing next generation vaccines: combining α-galactose modified antigens with nanoparticle platforms.

Sci Rep. 2014-1-20

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