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一种新型多糖平台构建自佐剂纳米疫苗以增强免疫应答。

A new polysaccharide platform constructs self-adjuvant nanovaccines to enhance immune responses.

机构信息

Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, 650000, Yunnan, China.

State Key Laboratory of Phytochemistry and Plant Resources in West China, and Yunnan Key Laboratory of Natural Medicinal Chemistry, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650201, Yunnan, China.

出版信息

J Nanobiotechnology. 2022 Jul 14;20(1):320. doi: 10.1186/s12951-022-01533-3.

Abstract

BACKGROUND

Nanovaccines have shown the promising potential in controlling and eradicating the threat of infectious diseases worldwide. There has been a great need in developing a versatile strategy to conveniently construct diverse types of nanovaccines and induce potent immune responses. To that end, it is critical for obtaining a potent self-adjuvant platform to assemble with different types of antigens into nanovaccines.

RESULTS

In this study, we identified a new natural polysaccharide from the rhizomes of Bletilla striata (PRBS), and used this polysaccharide as a platform to construct diverse types of nanovaccines with potent self-adjuvant property. In the construction process of SARS-CoV-2 nanovaccine, PRBS molecules and RBD protein antigens were assembled into ~ 300 nm nanoparticles by hydrogen bond. For HIV nanovaccine, hydrophobic effect dominantly drove the co-assembly between PRBS molecules and Env expression plasmid into ~ 350 nm nanospheres. Importantly, PRBS can potently activate the behaviors and functions of multiple immune cells such as macrophages, B cells and dendritic cells. Depending on PRBS-mediated immune activation, these self-adjuvant nanovaccines can elicit significantly stronger antigen-specific antibody and cellular responses in vivo, in comparison with their corresponding traditional vaccine forms. Moreover, we also revealed the construction models of PRBS-based nanovaccines by analyzing multiple assembly parameters such as bond energy, bond length and interaction sites.

CONCLUSIONS

PRBS, a newly-identified natural polysaccharide which can co-assemble with different types of antigens and activate multiple critical immune cells, has presented a great potential as a versatile platform to develop potent self-adjuvant nanovaccines.

摘要

背景

纳米疫苗在控制和消除全球传染病威胁方面显示出了巨大的潜力。开发一种通用策略来方便地构建不同类型的纳米疫苗并诱导有效的免疫反应非常重要。为此,获得一种有效的自佐剂平台,将不同类型的抗原组装成纳米疫苗至关重要。

结果

在这项研究中,我们从白芨根茎中鉴定出一种新型天然多糖(PRBS),并将该多糖用作平台,构建具有强大自佐剂特性的多种类型的纳米疫苗。在 SARS-CoV-2 纳米疫苗的构建过程中,PRBS 分子和 RBD 蛋白抗原通过氢键组装成300nm 的纳米颗粒。对于 HIV 纳米疫苗,疏水力主要驱动 PRBS 分子和 Env 表达质粒共组装成350nm 的纳米球。重要的是,PRBS 可以强烈激活多种免疫细胞(如巨噬细胞、B 细胞和树突状细胞)的行为和功能。依赖于 PRBS 介导的免疫激活,这些自佐剂纳米疫苗在体内可引起明显更强的抗原特异性抗体和细胞反应,与它们相应的传统疫苗形式相比。此外,我们还通过分析键能、键长和相互作用位点等多个组装参数,揭示了基于 PRBS 的纳米疫苗的构建模型。

结论

PRBS 是一种新鉴定的天然多糖,可与不同类型的抗原共组装并激活多种关键免疫细胞,它作为一种通用平台,具有很大的潜力用于开发有效的自佐剂纳米疫苗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/80c9/9281129/ca0cce0e4ca0/12951_2022_1533_Fig1_HTML.jpg

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