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古菌脂质黏膜疫苗佐剂和传递系统。

Archaeal lipid mucosal vaccine adjuvant and delivery system.

机构信息

Institute for Biological Sciences, National Research Council Canada, 100 Sussex Drive, Ottawa, ON K1A 0R6, Canada.

出版信息

Expert Rev Vaccines. 2010 Apr;9(4):431-40. doi: 10.1586/erv.10.34.

DOI:10.1586/erv.10.34
PMID:20370552
Abstract

Archaeal polar lipids are being evaluated as adjuvants/vaccine delivery systems for mucosal vaccines that can provide protection against pathogens that enter the human host via the mucosal surfaces. Archaeosomes, liposomes made from polar lipids extracted from Archaea, with encapsulated antigens elicit strong antigen-specific systemic immune responses upon systemic or intranasal immunization, but fail to generate mucosal immune responses. However, intranasal immunization of mice with the archaeal lipid mucosal vaccine adjuvant and delivery (AMVAD) system, obtained by the interaction of archaeosomes/antigens with multivalent cations, induces robust, antigen-specific IgA responses in nasal and vaginal mucosa, feces, bile, and serum. In addition, strong antigen-specific systemic antibody (serum IgG, IgG(1) and IgG(2a)) and cell-mediated responses, including CD8(+) cytotoxic T lymphocyte, are generated. The responses are sustained over time and are subject to good memory-boost responses. The AMVAD formulations are stable during storage, have a good safety profile and show protective efficacy in a murine model of infection/challenge.

摘要

古菌极性脂类作为黏膜疫苗的佐剂/疫苗传递系统正在得到评估,这些疫苗可以为通过黏膜表面进入人体宿主的病原体提供保护。由古菌提取的极性脂类制成的类脂体(archaeosomes),与包封的抗原一起,在全身或鼻内免疫后会引发强烈的抗原特异性全身免疫应答,但不能产生黏膜免疫应答。然而,通过类脂体/抗原与多价阳离子的相互作用获得的古菌脂质黏膜疫苗佐剂和传递(AMVAD)系统,经鼻内免疫小鼠,可在鼻和阴道黏膜、粪便、胆汁和血清中诱导出强大的、抗原特异性的 IgA 应答。此外,还会产生强烈的抗原特异性全身抗体(血清 IgG、IgG(1)和 IgG(2a))和细胞介导的应答,包括 CD8+细胞毒性 T 淋巴细胞。这些应答随时间持续,并受到良好的记忆增强应答的影响。AMVAD 制剂在储存过程中稳定,具有良好的安全性,并在感染/挑战的小鼠模型中显示出保护效力。

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