测试聚糖辅助剂的结构元素,以增强呼吸道粘膜反应:从克服多个障碍物到引起级联免疫力
Zhixiang Cui1, Hezhi Wang1, Lu Qin1
1School of Pharmacy, Shenyang Key Laboratory of Intelligent Mucosal Drug Delivery Systems, Shenyang Pharmaceutical University, Shenyang 110016, China.
ACS nano
|March 10, 2025
概括
聚糖中的硫酸盐群显著增强免疫激活,使它们成为有希望的肺疫苗辅助剂. 用硫酸 (SH) 修饰的纳米疫苗显示出优异的免疫反应和免疫记忆的潜力.
科学领域:
- 免疫学 免疫学 免疫学
- 材料科学 材料科学 材料科学
- 生物化学 生物化学
背景情况:
- 多糖是理想的肺疫苗辅助剂,因为它们的免疫调节作用和耐受性.
- 多糖结构与免疫刺激活性之间的确切关系尚未完全理解.
- 开发有效的肺部疫苗输送系统需要了解多糖结构如何影响免疫反应.
研究的目的:
- 研究不同多糖类作为纳米疫苗辅助剂的结构-免疫刺激活性关系.
- 评估多糖化物装饰的纳米疫苗在增强肺免疫反应方面的有效性.
- 阐明聚糖介导免疫激活的基础分子机制.
主要方法:
- 纳米疫苗的开发装饰着四种不同的多糖:氨酸 (HA),pectin (PC),chondroitin硫酸盐 (SC) 和heparan硫酸盐 (SH).
- 评估纳米疫苗的特性,包括粒子大小和泽塔潜力.
- 在实验室测试树突细胞 (DC) 招募和刺激,包括细胞因子分泌 (IL-6) 和共刺激分子表达.
- 在体内研究评估DC迁移,免疫细胞激活和幽默/细胞免疫反应.
- 分子对接和西部斑分析以确定涉及的信号通路 (TLR-MyD88-TRAF6-NF-κB/MAPK/IRF-7).
主要成果:
- 具有硫酸盐群的多糖类 (SC,SH) 显示出克服吸入障碍和招募DC的增强能力.
- 肝硫酸 (SH) 和氨酸 (HA) 显著上调了直流共刺激信号和IL-6分泌.
- SH修饰的纳米疫苗在体内表现出优异的免疫反应,包括CCR7上调,淋巴结迁移和具有免疫记忆的强大的细胞/幽默免疫力.
- 信号通路分析证实了TLR-MyD88-TRAF6-NF-κB/MAPK/IRF-7参与SH介导的免疫激活.
- 硫酸盐组被确定为增强免疫激活的关键贡献者.
结论:
- 聚糖中的硫酸盐群对于增强免疫激活和改善肺疫苗辅助剂疗效至关重要.
- 肝硫酸盐 (SH) 成为一种强大的辅助剂,显著增强细胞和幽默免疫力.
- 将硫酸盐和乙烯基组结合到多糖体中,为开发先进的粘膜和全身疫苗辅助剂提供了一个有希望的策略.
更多相关视频
11:26Harvesting Murine Alveolar Macrophages and Evaluating Cellular Activation Induced by Polyanhydride Nanoparticles
Published on: June 8, 2012
19.8K
07:32Evaluating the Immune Response of a Nanoemulsion Adjuvant Vaccine Against Methicillin-Resistant Staphylococcus aureus MRSA Infection
Published on: September 1, 2023
1.7K
相关概念视频
Antigens Involved in Adaptive Immunity
434
An antigen is any substance the immune system identifies as foreign and potentially harmful to the body, prompting an immune response. Antigens have two functional properties: immunogenicity and reactivity. Immunogenicity is the ability of an antigen to stimulate a specific immune response. At the same time, reactivity describes the antigen's ability to react with the cells and antibodies produced in response to it.
Complete Antigens
Complete antigens possess both immunogenicity and...
Complete Antigens
Complete antigens possess both immunogenicity and...
434
Glycosaminoglycans
4.7K
Glycosaminoglycans (GAGs), also known as mucopolysaccharides, are long and linear polymers comprising of specific repeating disaccharides - the amino sugar that can be N-acetylglucosamine or N-acetylgalactosamine, and a uronic acid that is usually glucuronic acid or iduronic acid.
GAGS are found in the extracellular matrix of vertebrates, invertebrates, and bacteria. Due to their polar nature they attract water, and serve as excellent lubricants or shock absorbers in an animal body.
Hyaluronic...
GAGS are found in the extracellular matrix of vertebrates, invertebrates, and bacteria. Due to their polar nature they attract water, and serve as excellent lubricants or shock absorbers in an animal body.
Hyaluronic...
4.7K
Oligosaccharide Assembly
2.7K
Protein glycosylation starts in the ER lumen and continues in the Golgi apparatus. Glycosyltransferases catalyze the addition of sugar molecules or glycosylation of proteins. Usually, these enzymes add sugars to the hydroxyl groups of selected serine or threonine residues to form O-linked glycans or the amino groups of asparagine residues to form N-linked glycans. Different positions on the same polypeptide chain can contain differently linked glycans.
Multiple sugar molecules that may or may...
Multiple sugar molecules that may or may...
2.7K
Proteoglycans
3.8K
Glycans, a class of complex heterogeneous molecules, can be covalently attached to proteins to form glycosylated proteins that regulate various physiological and pathological processes. Glycosylated proteins or glycoproteins comprise N-linked and O-linked oligosaccharides. O-glycosylation is the most common type of protein glycosylation. Here, glycans attach to the oxygen atom of the hydroxyl groups of Serine or Threonine residues. O-linked glycosylation occurs later in protein processing,...
3.8K
Upper Respiratory Drugs: Antitussives, Expectorants, and Mucolytics
213
Respiratory symptoms, such as congestion and cough, commonly accompany respiratory tract conditions. Various medications, such as antitussives, expectorants, and mucolytics, play crucial roles in providing relief.
Antitussives include codeine, dextromethorphan (Robitussin), and benzonatate (Tessalon). Codeine and dextromethorphan exert their effects centrally by suppressing the cough reflex center in the medulla. Benzonatate operates peripherally within the respiratory tract by...
Antitussives include codeine, dextromethorphan (Robitussin), and benzonatate (Tessalon). Codeine and dextromethorphan exert their effects centrally by suppressing the cough reflex center in the medulla. Benzonatate operates peripherally within the respiratory tract by...
213
