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利用脑膜炎奈瑟菌 B 群的类脂体和空斑结构进行黏膜免疫接种可诱导黏膜和全身应答。

Mucosal immunization using proteoliposome and cochleate structures from Neisseria meningitidis serogroup B induce mucosal and systemic responses.

机构信息

Immunology Department, Finlay Institute, PO Box 16017, Havana, Cuba.

出版信息

Methods. 2009 Dec;49(4):301-8. doi: 10.1016/j.ymeth.2009.03.025. Epub 2009 May 4.

DOI:10.1016/j.ymeth.2009.03.025
PMID:19410000
Abstract

Most pathogens either invade the body or establish infection in mucosal tissues and represent an enormous challenge for vaccine development by the absence of good mucosal adjuvants. A proteoliposome-derived adjuvant from Neisseria meningitidis serogroup B (AFPL1, Adjuvant Finlay Proteoliposome 1) and its derived cochleate form (Co, AFCo1) contain multiple pathogen-associated molecular patterns as immunopotentiators, and can also serve as delivery systems to elicit a Th1-type immune response. The present studies demonstrate the ability of AFPL1and AFCo1 to induce mucosal and systemic immune responses by different mucosal immunizations routes and significant adjuvant activity for antibody responses of both structures: a microparticle and a nanoparticle with a heterologous antigen. Therefore, we used female mice immunized by intragastric, intravaginal, intranasal or intramuscular routes with both structures alone or incorporated with ovalbumin (OVA). High levels of specific IgG antibody were detected in all sera and in vaginal washes, but specific IgA antibody in external secretions was only detected in mucosally immunized mice. Furthermore, antigen specific IgG1 and IgG2a isotypes were all induced. AFPL1 and AFCo1 are capable of inducing IFN-gamma responses, and chemokine secretions, like MIP-1alpha and MIP-1beta. However, AFCo1 is a better alternative to induce immune responses at mucosal level. Even when we use a heterologous antigen, the AFCo1 response was better than with AFPL1 in inducing mucosal and systemic immune responses. These results support the use of AFCo1 as a potent Th1 inducing adjuvant particularly suitable for mucosal immunization.

摘要

大多数病原体要么入侵身体,要么在黏膜组织中建立感染,由于缺乏良好的黏膜佐剂,这对疫苗的开发构成了巨大挑战。脑膜炎奈瑟菌 B 群(AFPL1,Neisseria meningitidis serogroup B)的一种蛋白脂质体衍生佐剂及其衍生的卷曲形式(Co,AFCo1)含有多种病原体相关分子模式作为免疫增强剂,也可以作为递呈系统来引发 Th1 型免疫反应。本研究通过不同的黏膜免疫途径证明了 AFPL1 和 AFCo1 诱导黏膜和全身免疫反应的能力,以及这两种结构(一种微粒和一种纳米颗粒,具有异源抗原)的抗体反应的显著佐剂活性。因此,我们使用雌性小鼠通过口服、阴道、鼻内或肌肉途径单独或与卵清蛋白(OVA)一起免疫这两种结构。在所有血清和阴道洗液中都检测到高水平的特异性 IgG 抗体,但只有在黏膜免疫的小鼠中才检测到外分泌液中的特异性 IgA 抗体。此外,还诱导了抗原特异性 IgG1 和 IgG2a 同型。AFPL1 和 AFCo1 能够诱导 IFN-γ反应和趋化因子分泌,如 MIP-1alpha 和 MIP-1beta。然而,AFCo1 是诱导黏膜水平免疫反应的更好选择。即使我们使用异源抗原,AFCo1 的反应也优于 AFPL1,能够诱导黏膜和全身免疫反应。这些结果支持使用 AFCo1 作为一种有效的 Th1 诱导佐剂,特别适合黏膜免疫。

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