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开发并免疫生物学评价含有单纯疱疹病毒免疫优势表位的纳米颗粒。

Development and immunobiological evaluation of nanoparticles containing an immunodominant epitope of herpes simplex virus.

机构信息

Laboratorio de Imunovirologia, Universidade Federal de Ciências da Saúde de Porto Alegre, Brazil.

Laboratório de Nanotecnologia, Universidade Franciscana, Brazil.

出版信息

IET Nanobiotechnol. 2021 Aug;15(6):532-544. doi: 10.1049/nbt2.12043. Epub 2021 Mar 30.

DOI:10.1049/nbt2.12043
PMID:34694744
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8675790/
Abstract

Herpes simplex virus (HSV) 1 and 2 are viruses that infect individuals worldwide and for which there is no cure or vaccine available. The protective response against herpes is mostly mediated by CD8 T lymphocytes that respond to the immunodominant SSIEFARL epitope. However, there are some obstacles concerning the use of free SSIEFARL for vaccine or immunotherapy. The aim of this study was to evaluate the feasibility of nanoencapsulation of SSIEFARL and its immunostimulatory properties. Nano/SSIEFARL was produced by interfacial polymerization in methylmetacrylate, and the physico-chemical properties, morphology and immunobiological parameters were evaluated. To evaluate the ex vivo capacity of Nano/SSIEFARL, we used splenocytes from HSV-1-infected mice to enhance the frequency of SSIEFARL-specific CD8 T lymphocytes. The results indicate that Nano/SSIEFARL has a spherical shape, an average diameter of 352 ± 22 nm, the PDI was 0.361 ± 0.009 and is negatively charged (-26.30 ± 35). The stability at 4°C was 28 days. Also, Nano/SSIEFARL is not toxic for cells at low concentrations in vitro and it is taken up by JAWS II dendritic cells. No histopathological changes were observed in kidneys, liver and lymph nodes of animals treated with Nano/SSIEFARL. Nan/SSIEFARL increased the production of IL-1β, TNF-α and IL-12 by the dendritic cells. Finally, Nano/SSIEFARL expanded the frequency of SSIEFARL-specific CD8+T lymphocytes at the same rate as free SSIEFARL. In conclusion all data together indicate that SSIEFARL is suitable for nanoencapsulation, and the system produced presents some immunoadjuvant properties that can be used to improve the immune response against herpes.

摘要

单纯疱疹病毒 (HSV) 1 和 2 是感染全球人群的病毒，目前尚无治愈或疫苗可用。针对疱疹的保护反应主要由 CD8 T 淋巴细胞介导，这些细胞对免疫显性 SSIEFARL 表位作出反应。然而，在使用游离 SSIEFARL 作为疫苗或免疫疗法方面存在一些障碍。本研究旨在评估 SSIEFARL 纳米包封及其免疫刺激特性的可行性。通过甲基丙烯酸甲酯的界面聚合生产 Nano/SSIEFARL，并对其物理化学性质、形态和免疫生物学参数进行评估。为了评估 Nano/SSIEFARL 的体外能力，我们使用 HSV-1 感染小鼠的脾细胞来增强 SSIEFARL 特异性 CD8 T 淋巴细胞的频率。结果表明，Nano/SSIEFARL 呈球形，平均直径为 352±22nm，PDI 为 0.361±0.009，带负电荷 (-26.30±35)。在 4°C 下的稳定性为 28 天。此外，Nano/SSIEFARL 在体外低浓度下对细胞无毒，并且被 JAWS II 树突状细胞摄取。用 Nano/SSIEFARL 处理的动物的肾脏、肝脏和淋巴结未观察到组织病理学变化。Nano/SSIEFARL 增加了树突状细胞产生的 IL-1β、TNF-α 和 IL-12。最后，Nano/SSIEFARL 以与游离 SSIEFARL 相同的速率扩展了 SSIEFARL 特异性 CD8+T 淋巴细胞的频率。总之，所有数据表明 SSIEFARL 适合纳米包封，所产生的系统具有一些免疫佐剂特性，可用于改善针对疱疹的免疫反应。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8cee/8675790/22f30dc5e4aa/NBT2-15-532-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8cee/8675790/a1e40aac3f5c/NBT2-15-532-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8cee/8675790/6e21a26b0808/NBT2-15-532-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8cee/8675790/6dae6ca7582b/NBT2-15-532-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8cee/8675790/1af3426a6148/NBT2-15-532-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8cee/8675790/628511bb8f7d/NBT2-15-532-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8cee/8675790/9b7e52557f63/NBT2-15-532-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8cee/8675790/22f30dc5e4aa/NBT2-15-532-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8cee/8675790/a1e40aac3f5c/NBT2-15-532-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8cee/8675790/6e21a26b0808/NBT2-15-532-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8cee/8675790/6dae6ca7582b/NBT2-15-532-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8cee/8675790/1af3426a6148/NBT2-15-532-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8cee/8675790/628511bb8f7d/NBT2-15-532-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8cee/8675790/9b7e52557f63/NBT2-15-532-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8cee/8675790/22f30dc5e4aa/NBT2-15-532-g004.jpg

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