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基于酵母β-葡聚糖颗粒的新型佐剂诱导乙型肝炎疫苗产生的稳健免疫应答。

Robust Immune Responses Elicited by a Hybrid Adjuvant Based on β-Glucan Particles from Yeast for the Hepatitis B Vaccine.

机构信息

Henan Key Laboratory of Immunology and Targeted Drug, Henan Collaborative Innovation Center of Molecular Diagnosis and Laboratory Medicine, School of Laboratory Medicine, Xinxiang Medical University, Xinxiang, Henan 453003, China.

State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin 300071, China.

出版信息

ACS Appl Bio Mater. 2021 Apr 19;4(4):3614-3622. doi: 10.1021/acsabm.1c00111. Epub 2021 Apr 6.

Abstract

The use of particulate adjuvants offers an interesting method for enhancing and modulating the immune responses elicited by vaccines. Aluminum salt (Alum) is one of the most important immune adjuvants approved by the Food and Drug Administration for use in humans because of its safety and efficacy, but it lacks the capacity to induce strong cellular and mucosal immune responses. In this study, we designed an antigen delivery system that combines aluminum salts with β-glucan particles. The β-glucan-aluminum particles (GP-Al) exhibited a highly uniform size of 2-4 μm and could highly specifically target antigen-presenting cells (APCs) and strongly induce dendritic cell (DC) maturation and cytokine secretion. studies showed that both WT mice and HBV-Tg mice immunized with hepatitis B surface antigen (HBsAg)-containing GP-Al displayed high anti-HBsAg IgG titers in the serum. Furthermore, in contrast to mice receiving the antigen alone, mice immunized with the particulate adjuvant exhibited IgG2a antibody titers and higher antigen-specific IFN-γ levels in splenocytes. In conclusion, we developed GP-Al microspheres to serve as a hepatitis B vaccine to enhance both humoral and cellular immune responses, representing a safe and promising system for antigen delivery.

摘要

颗粒佐剂的使用为增强和调节疫苗引起的免疫反应提供了一种有趣的方法。铝盐(明矾)是食品和药物管理局批准用于人类的最重要的免疫佐剂之一,因为它的安全性和有效性,但它缺乏诱导强烈的细胞和粘膜免疫反应的能力。在这项研究中,我们设计了一种将铝盐与β-葡聚糖颗粒结合的抗原递送系统。β-葡聚糖-铝颗粒(GP-Al)表现出高度均匀的 2-4μm 大小,能够高度特异性地靶向抗原呈递细胞(APC),并强烈诱导树突状细胞(DC)成熟和细胞因子分泌。研究表明,用含有乙型肝炎表面抗原(HBsAg)的 GP-Al 免疫的 WT 小鼠和 HBV-Tg 小鼠在血清中均显示出高抗-HBsAg IgG 滴度。此外,与仅接受抗原的小鼠相比,用颗粒佐剂免疫的小鼠在脾细胞中显示出 IgG2a 抗体滴度和更高的抗原特异性 IFN-γ 水平。总之,我们开发了 GP-Al 微球作为乙型肝炎疫苗,以增强体液和细胞免疫反应,代表了一种安全有前途的抗原递送系统。

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