工程治療性納米疫苗可抵抗慢性乙型肝炎病毒感染

StephenW

Engineered therapeutic nanovaccine against chronic hepatitis B virus infection
Dongdong Qiao  1 , Yongming Chen  2 , Lixin Liu  3
Affiliations
Affiliations

    1
    School of Materials Science and Engineering, Key Laboratory for Polymer Composite and Functional Materials of Ministry of Education, GD Research Center for Functional Biomaterials Engineering and Technology, Sun Yat-sen University, Guangzhou, 510275, China.
    2
    School of Materials Science and Engineering, Key Laboratory for Polymer Composite and Functional Materials of Ministry of Education, GD Research Center for Functional Biomaterials Engineering and Technology, Sun Yat-sen University, Guangzhou, 510275, China. Electronic address: [email protected].
    3
    School of Materials Science and Engineering, Key Laboratory for Polymer Composite and Functional Materials of Ministry of Education, GD Research Center for Functional Biomaterials Engineering and Technology, Sun Yat-sen University, Guangzhou, 510275, China. Electronic address: [email protected].

    PMID: 33486345 DOI: 10.1016/j.biomaterials.2021.120674

Abstract

Chronic hepatitis B (CHB), caused by persistent hepatitis B virus (HBV) infection, significantly increases the risk of leading to liver diseases. Despite the successful development and implementation of HBV prophylactic vaccines for several decades, the development of therapeutic vaccine, a substantially potential strategy to eradicate HBV and achieve CHB cure, remains a great challenge. Herein, we applied flash nanocomplexation (FNC) technology to prepare nanovaccines with narrow size distribution and high encapsulation via the charge complexation between chitosan and heparin to encapsulate recombinant hepatitis B virus surface antigen (rHBsAg) or core antigen (rHBcAg), with CpG as adjuvant. The two nanovaccines enhanced the uptake of antigen and adjuvant into Raw264.7 cells and their co-administration further promoted maturation and activation of bone marrow-derived dendritic cells (BMDCs). Meanwhile, they exhibited excellent lymph nodes (LNs) targeting ability, draining to proximal and distal LNs with prolonged retention time, following subcutaneous injection. Co-administered nanovaccines could break immune tolerance and restore HBV-specific immune responses. In a mouse model of CHB, 90% and 80% of mice achieved hepatitis B virus surface antigen (HBsAg) seroclearance and hepatitis B virus surface antibody (HBsAb) seroconversion, respectively. Moreover, the vaccines induced long-term immune memory in HBV-cured mice to protect them from HBV reinfection. Thus, this work offers a promising and translational alternative for therapeutic CHB vaccine.

Keywords: Chronic hepatitis B; Co-administration; Flash nanocomplexation; Lymph node targeting; Therapeutic nanovaccine.

Copyright © 2021 Elsevier Ltd. All rights reserved.

StephenW

工程治療性納米疫苗可抵抗慢性乙型肝炎病毒感染
喬東東1，陳永明2，劉立新3
隸屬關係
隸屬關係

    1個
    中山大學材料科學與工程學院，高分子復合材料與功能材料教育部重點實驗室，中山大學GD功能生物材料工程與技術研究中心，廣州510275
    2
    中山大學材料科學與工程學院，高分子復合材料與功能材料教育部重點實驗室，中山大學GD功能生物材料工程與技術研究中心，廣州510275電子地址：[email protected]。
    3
    中山大學材料科學與工程學院，高分子復合材料與功能材料教育部重點實驗室，中山大學GD功能生物材料工程與技術研究中心，廣州510275電子地址：[email protected]。

    PMID：33486345 DOI：10.1016 / j.biomaterials.2021.120674

抽象

由持續性乙型肝炎病毒（HBV）感染引起的慢性乙型肝炎（CHB）大大增加了導致肝臟疾病的風險。儘管數十年來成功開發和實施了HBV預防性疫苗，但治療性疫苗的開發仍然是一項巨大的挑戰，而治療性疫苗是根除HBV並實現CHB治癒的基本潛在策略。在本文中，我們應用快速納米複合（FNC）技術通過殼聚醣和肝素之間的電荷絡合製備具有窄尺寸分佈和高包封率的納米疫苗，從而以CpG為佐劑包封重組乙型肝炎病毒表面抗原（rHBsAg）或核心抗原（rHBcAg） 。這兩種納米疫苗增強了Raw264.7細胞對抗原和佐劑的吸收，它們的共同給藥進一步促進了骨髓源性樹突狀細胞（BMDC）的成熟和激活。同時，他們表現出出色的淋巴結（LNs）靶向能力，皮下注射後排泄到近端和遠端的LNs，保留時間延長。並用納米疫苗可以破壞免疫耐受並恢復HBV特異性免疫反應。在CHB小鼠模型中，分別有90％和80％的小鼠實現了乙型肝炎病毒表面抗原（HBsAg）血清清除和B型肝炎病毒表面抗體（HBsAb）血清轉化。此外，這些疫苗在HBV治癒的小鼠中誘導了長期的免疫記憶，以保護它們免受HBV再感染。因此，這項工作為治療性CHB疫苗提供了有希望的翻譯替代方案。

關鍵字：慢性乙型肝炎；共同管理；閃光納米複合；淋巴結靶向；治療性納米疫苗。

版權所有©2021 ElsevierLtd。保留所有權利。