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Mucosal and systemic immune responses by intranasal immunization using archaeal lipid-adjuvanted vaccines

机译:使用古生脂质佐剂的鼻内免疫进行粘膜和全身免疫反应

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摘要

The utility of archaeal polar lipids as an adjuvant/delivery system for elicitation of antigen-specific mucosal immune responses in intranasally administered vaccines was investigated. Although unilamellar archaeosomes (liposomes made from archaeal polar lipids) with encapsulated ovalbumin (OVA/archaeosomes) induced anti-OVA IgG antibody responses in sera, they failed to induce anti-OVA IgA antibody responses at mucosal sites. However, the addition of CaCl2 to convert OVA/archaeosomes into an archaeal lipid mucosal vaccine adjuvant and delivery (AMVAD) vaccine (OVA/AMVAD) consisting of larger, particulate, aggregated structures resulted in an efficacious intranasal (i.n.) vaccine. Intranasal immunization of mice with OVA/AMVAD vaccines prepared from various archaeal polar lipid compositions elicited anti-OVA IgA antibody responses in sera, feces, bile, vaginal and nasal wash samples. The i.n. immunization also induced anti-OVA IgG, IgG1 and IgG2a antibody responses in sera, as well as cytotoxic T lymphocyte responses. The mucosal and systemic immune responses induced by OVA/AMVAD immunization were generally sustained over several months, and were subject to memory boost responses. Thus, polar archaeal lipids appear to be promising for developing a non-replicating mucosal adjuvant and vaccine delivery system.
机译:研究了古细菌极性脂质作为佐剂/递送系统在鼻内接种疫苗中引发抗原特异性粘膜免疫反应的效用。尽管单层古生物体(由古细菌极性脂质制成的脂质体)与包囊的卵清蛋白(OVA /古生物体)在血清中诱导抗OVA IgG抗体反应,但它们未能在粘膜部位诱导抗OVA IgA抗体反应。但是,添加CaCl2将OVA /古菌体转化为古脂类脂质粘膜疫苗佐剂和转运(AMVAD)疫苗(OVA / AMVAD),后者由较大的颗粒状聚集结构组成,形成了有效的鼻内(i.n.)疫苗。用从各种古细菌极性脂质组合物制备的OVA / AMVAD疫苗对小鼠进行鼻内免疫,可在血清,粪便,胆汁,阴道和鼻腔清洗样品中引起抗OVA IgA抗体反应。 i.n.免疫还诱导了血清中抗OVA IgG,IgG1和IgG2a抗体反应,以及细胞毒性T淋巴细胞反应。由OVA / AMVAD免疫诱导的粘膜和全身免疫反应通常持续数月,并经历记忆增强反应。因此,极地古细菌脂质似乎有望用于开发非复制性粘膜佐剂和疫苗递送系统。

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