基于来自酵母的 β-葡聚糖颗粒的混合佐剂对乙型肝炎疫苗的

StephenW

基于来自酵母的 β-葡聚糖颗粒的混合佐剂对乙型肝炎疫苗的强烈免疫反应
刘慧 1 2 , 孟子玉 2 3 , 王何穗源 2 , 张硕 1 , 黄震 1 , 耿晓芳 1 , 郭睿 4 , 吴振洲 2 , 张永红 2
隶属关系
隶属关系

    1
    新乡医科大学检验医学学院, 河南省分子诊断与检验医学协同创新中心, 河南省免疫学与靶向药物重点实验室, 河南新乡 453003
    2
    南开大学生命科学学院, 药物化学生物学国家重点实验室, 天津 300071
    3
    天津医科大学朱显一纪念医院、天津市内分泌研究所，国家卫生健康委员会激素与发育重点实验室，天津市代谢疾病重点实验室，天津医科大学，天津 300134
    4
    新乡医科大学生物医学工程学院，河南新乡 453003

    PMID：35014447 DOI：10.1021/acsabm.1c00111

抽象的

颗粒佐剂的使用为增强和调节疫苗引发的免疫反应提供了一种有趣的方法。铝盐 (Alum) 是美国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) 具有高度均匀的 2-4 μm 尺寸，可以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。体内研究表明，用含有乙型肝炎表面抗原 (HBsAg) 的 GP-A1 免疫的 WT 小鼠和 HBV-Tg 小鼠在血清中都显示出高抗 HBsAg IgG 滴度。此外，与单独接受抗原的小鼠相比，用颗粒佐剂免疫的小鼠在脾细胞中表现出 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，代表了一种安全且有前景的抗原递送系统。

关键词：铝助剂；细胞免疫反应；树突状细胞；葡聚糖；乙肝疫苗。

StephenW

Robust Immune Responses Elicited by a Hybrid Adjuvant Based on β-Glucan Particles from Yeast for the Hepatitis B Vaccine
Hui Liu  1   2 , Ziyu Meng  2   3 , Hesuiyuan Wang  2 , Shuo Zhang  1 , Zhen Huang  1 , Xiaofang Geng  1 , Rui Guo  4 , Zhenzhou Wu  2 , Zhangyong Hong  2
Affiliations
Affiliations

    1
    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.
    2
    State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin 300071, China.
    3
    NHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Tianjin Medical University Chu Hsien-I Memorial Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin 300134, China.
    4
    College of Biomedical Engineering, Xinxiang Medical University, Xinxiang, Henan 453003, China.

    PMID: 35014447 DOI: 10.1021/acsabm.1c00111

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. In vivo 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.

Keywords: aluminum adjuvant; cellular immune response; dendritic cell; glucan; hepatitis B vaccine.