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用牙龈卟啉单胞菌40 kDa外膜蛋白加霍乱毒素进行鼻腔免疫可诱导老年小鼠产生保护性免疫。

Nasal immunization with the 40-kDa outer membrane protein of Porphyromonas gingivalis plus cholera toxin induces protective immunity in aged mice.

作者信息

Cai Yu, Kurita-Ochiai Tomoko, Kobayashi Ryoki, Hashizume Tomomi, Yamamoto Masafumi

机构信息

Department of Microbiology and Immunology, Nihon University School of Dentistry at Matsudo, Matsudo, Japan.

出版信息

J Oral Sci. 2013;55(2):107-14. doi: 10.2334/josnusd.55.107.

DOI:10.2334/josnusd.55.107
PMID:23748449
Abstract

Previous studies have demonstrated that nasal administration of the outer membrane protein of Porphyromonas gingivalis (40k-OMP) with cholera toxin (CT) as an adjuvant elicits protective immune responses against P. gingivalis in young mice. In the present study, we investigated whether administration of 40k-OMP plus CT would also induce 40k-OMP-specific antibody (Ab) responses to provide protective immunity against P. gingivalis infection in aged mice. Nasal immunization with 40k-OMP plus CT elicited 40k-OMP-specific IgG and IgA Ab responses in serum and a significant anti-40k-OMP IgA Ab response in nasal washes and saliva in 1- and 2-year-old mice. Furthermore, both Th1- and Th2-type cytokine responses were induced by the immunization, and cytokine-associated IgG1, IgG2a, and IgG2b Ab responses were observed in the spleens of aged mice. Although the aged mice showed lower 40k-OMP-specific Ab responses than young mice, their mucosal IgA Ab titers as well as serum IgG Ab responses indicated a retained ability to mediate protective immunity; the only exception was saliva in 2-year-old mice. These findings suggest that nasal immunization with 40k-OMP plus CT can be a potential vaccination strategy for eliciting levels of Abs sufficient to provide protective immunity against P. gingivalis infection in aged mice.

摘要

先前的研究表明,以霍乱毒素(CT)作为佐剂经鼻腔给予牙龈卟啉单胞菌外膜蛋白(40k-OMP)可在幼龄小鼠中引发针对牙龈卟啉单胞菌的保护性免疫反应。在本研究中,我们调查了给予40k-OMP加CT是否也会诱导40k-OMP特异性抗体(Ab)反应,从而为老年小鼠提供针对牙龈卟啉单胞菌感染的保护性免疫。用40k-OMP加CT进行鼻腔免疫在1岁和2岁小鼠的血清中引发了40k-OMP特异性IgG和IgA Ab反应,在鼻腔灌洗液和唾液中引发了显著的抗40k-OMP IgA Ab反应。此外,免疫诱导了Th1型和Th2型细胞因子反应,并且在老年小鼠的脾脏中观察到了与细胞因子相关的IgG1、IgG2a和IgG2b Ab反应。尽管老年小鼠显示出比幼龄小鼠更低的40k-OMP特异性Ab反应,但其黏膜IgA Ab滴度以及血清IgG Ab反应表明其仍保留介导保护性免疫的能力;唯一的例外是2岁小鼠的唾液。这些发现表明,用40k-OMP加CT进行鼻腔免疫可能是一种潜在的疫苗接种策略,可引发足以在老年小鼠中提供针对牙龈卟啉单胞菌感染的保护性免疫的抗体水平。

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