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布鲁氏菌属的鲁马嗪合酶:一种有效诱导口服免疫的新型佐剂和抗原递送系统。

Brucella spp. lumazine synthase: a novel adjuvant and antigen delivery system to effectively induce oral immunity.

作者信息

Rosas Gabriela, Fragoso Gladis, Ainciart Natalia, Esquivel-Guadarrama Fernando, Santana Angélica, Bobes Raúl J, Ramírez-Pliego Oscar, Toledo Andrea, Cruz-Revilla Carmen, Meneses Gabriela, Berguer Paula, Goldbaum Fernando A, Sciutto Edda

机构信息

Facultad de Medicina, Universidad Autónoma del Estado de Morelos, 62210 Cuernavaca, Morelos, México.

出版信息

Microbes Infect. 2006 Apr;8(5):1277-86. doi: 10.1016/j.micinf.2005.12.006. Epub 2006 Feb 7.

Abstract

Brucella lumazine synthase (BLS) has been previously used with success as a delivery system for systemic immunization against murine cysticercosis. We herein determined the usefulness of BLS as a new antigen-delivery system and mucosal-adjuvant using KETc1, one of the peptides of the anti-cysticercosis vaccine. A protection of up to 98% was induced when KETc1 was used as a chimera fused to BLS. Used as adjuvant of KETc1, BLS also induced a high level of protection (79%), which did not significantly differ from that induced by the cholera toxin (74%). KETc1 and BLS administered separately also reduced the parasite load. KETc1 administered orally as a chimera, and to a lesser extent with BLS as adjuvant, elicited IgG and IgA specific antibodies, which were detectable both in fecal extracts and in sera, and increased B and CD4 activated cells. BLS-KETc1 also increased the levels of transcription of TNF-alpha, IL-2 and IFNgamma in Peyer's patches, and in spleen, only increased TNF-alpha was observed. Overall, these results showed that BLS can be used as both an antigen-carrier and as an adjuvant in the design of new oral subunit vaccines.

摘要

布鲁氏菌核黄素合酶(BLS)此前已成功用作全身性免疫接种抗小鼠囊尾蚴病的递送系统。我们在此使用抗囊尾蚴病疫苗的一种肽KETc1,确定了BLS作为一种新型抗原递送系统和黏膜佐剂的效用。当KETc1作为与BLS融合的嵌合体使用时,可诱导高达98%的保护率。用作KETc1的佐剂时,BLS也诱导了高水平的保护(79%),这与霍乱毒素诱导的保护率(74%)无显著差异。单独给予KETc1和BLS也降低了寄生虫负荷。作为嵌合体口服给予KETc1,以及在较小程度上与作为佐剂的BLS一起给予时,可引发IgG和IgA特异性抗体,这些抗体在粪便提取物和血清中均可检测到,并增加了B细胞和CD4活化细胞。BLS-KETc1还增加了派尔集合淋巴结中TNF-α、IL-2和IFNγ的转录水平,而在脾脏中,仅观察到TNF-α水平升高。总体而言,这些结果表明,BLS可在新型口服亚单位疫苗的设计中用作抗原载体和佐剂。

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