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用牙龈卟啉单胞菌外膜蛋白和Flt3配体进行舌下接种可在口腔中引发保护性免疫。

Sublingual vaccination with outer membrane protein of Porphyromonas gingivalis and Flt3 ligand elicits protective immunity in the oral cavity.

作者信息

Zhang Tao, Hashizume Tomomi, Kurita-Ochiai Tomoko, Yamamoto Masafumi

机构信息

Department of Microbiology and Immunology, Nihon University School of Dentistry at Matsudo, Chiba 271-8587, Japan.

出版信息

Biochem Biophys Res Commun. 2009 Dec 18;390(3):937-41. doi: 10.1016/j.bbrc.2009.10.081. Epub 2009 Oct 21.

Abstract

In this study, we demonstrated that the 40-kDa outer membrane protein of Porphyromonas gingivalis (40k-OMP) sublingually administered with a cDNA vector plasmid encoding Flt3 ligand (pFL) elicited a protective immune response. Sublingual immunization of mice with 40k-OMP plus pFL induced significant serum IgG and IgA, as well as salivary IgA, antibody responses that were comparable to those induced by 40k-OMP plus cholera toxin as adjuvant. When the subclasses of 40k-OMP-specific IgG were evaluated, sublingual immunization with 40k-OMP plus pFL induced both IgG1 and IgG2a antibody responses. Sublingual delivery of pFL resulted in FL expression in submandibular glands, but not in other oral tissues. Furthermore, marked increases in FL protein occurred in saliva and serum, and the frequencies of both CD11c(+)CD11b(+) and CD11c(+)CD8alpha(+) dendritic cells with up-regulated expression of CD80, CD86 and CD40 molecules significantly increased in submandibular lymph nodes and spleen. Importantly, the mice given sublingual 40k-OMP plus pFL showed a significant reduction of alveolar bone loss caused by oral infection with P. gingivalis. These findings suggest that sublingual administration of 40k-OMP with pFL acts as an effective and safe mucosal vaccine against oral P. gingivalis infection, and may be a useful tool in the prevention of chronic periodontitis.

摘要

在本研究中,我们证明了牙龈卟啉单胞菌40 kDa外膜蛋白(40k-OMP)与编码Flt3配体的cDNA载体质粒(pFL)舌下给药可引发保护性免疫反应。用40k-OMP加pFL对小鼠进行舌下免疫诱导了显著的血清IgG和IgA以及唾液IgA抗体反应,这些反应与用40k-OMP加霍乱毒素作为佐剂诱导的反应相当。当评估40k-OMP特异性IgG的亚类时,用40k-OMP加pFL进行舌下免疫诱导了IgG1和IgG2a抗体反应。pFL的舌下递送导致下颌下腺中FL表达,但在其他口腔组织中未表达。此外,唾液和血清中FL蛋白显著增加,下颌下淋巴结和脾脏中CD11c(+)CD11b(+)和CD11c(+)CD8α(+)树突状细胞的频率显著增加,且CD80、CD86和CD40分子的表达上调。重要的是,给予舌下40k-OMP加pFL的小鼠因牙龈卟啉单胞菌口腔感染引起的牙槽骨丧失显著减少。这些发现表明,40k-OMP与pFL舌下给药作为一种针对口腔牙龈卟啉单胞菌感染的有效且安全的黏膜疫苗,可能是预防慢性牙周炎的有用工具。

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