Archaeal lipid mucosal vaccine adjuvant and delivery system

Archaeal lipid mucosal vaccine adjuvant and delivery system
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古菌脂质粘膜疫苗佐剂和递送系统

DOI:
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发表时间:
2010
影响因子:
6.2
通讯作者:
Wangxue Chen
Wangxue Chen
中科院分区:
医学2区
文献类型:
--
作者:
G. B. Patel;Wangxue Chen

文献摘要

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正在评价粘膜极性脂质作为粘膜疫苗的佐剂/疫苗递送系统,其可以提供针对通过粘膜表面进入人类宿主的病原体的保护。古生物体是由从大肠杆菌中提取的极性脂质制成的脂质体,具有包封的抗原,在全身或鼻内免疫后引起强烈的抗原特异性全身免疫应答,但不能产生粘膜免疫应答。然而,通过古细菌体/抗原与多价阳离子的相互作用获得的古细菌脂质粘膜疫苗佐剂和递送(AMVAD)系统对小鼠进行鼻内免疫,在鼻和阴道粘膜、粪便、胆汁和血清中诱导稳健的抗原特异性伊加应答。此外,产生强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CD 8+细胞毒性T淋巴细胞。这些反应会随着时间的推移而持续,并且会受到良好的记忆增强反应的影响。AMVAD制剂在储存期间稳定,具有良好的安全性特征,并在感染/攻毒的鼠模型中显示出保护功效。
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, IgG1 and IgG2a) 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.