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通过鼻内给予牙龈卟啉单胞菌菌毛和重组霍乱毒素B亚基的小鼠诱导免疫反应并预防牙槽骨丧失

Induction of immune responses and prevention of alveolar bone loss by intranasal administration of mice with Porphyromonas gingivalis fimbriae and recombinant cholera toxin B subunit.

作者信息

Takahashi Y, Kumada H, Hamada N, Haishima Y, Ozono S, Isaka M, Yasuda Y, Tochikubo K, Umemoto T

机构信息

Department of Oral Microbiology, Kanagawa Dental College, Yokosuka, Kanagawa, Japan.

出版信息

Oral Microbiol Immunol. 2007 Dec;22(6):374-80. doi: 10.1111/j.1399-302X.2007.00373.x.

Abstract

INTRODUCTION

Adult periodontitis is initiated by specific periodontal pathogens represented by Porphyromonas gingivalis; however, an effective measure for preventing the disease has not yet been established. In this study, the effectiveness of a vaccine composed of fimbriae of P. gingivalis and recombinant cholera toxin B subunit (rCTB) was evaluated using BALB/c mice.

METHODS

Fimbriae and rCTB were co-administered intranasally to BALB/c mice on days 0, 14, 21, and 28. On day 35, mice were sacrificed to determine immunoglobulin levels in serum, saliva, and nasal and lung extracts by enzyme-linked immunosorbent assay. The prevention effect of the vaccine on P. gingivalis-induced periodontitis in mice was evaluated by measuring alveolar bone loss.

RESULTS

The rCTB significantly increased serum immunoglobulin (Ig)A levels when mice were administered with a minimal amount (0.5 microg) of the fimbrial antigen. The adjuvant effect on serum IgG production was indistinct because the minimal amount of the antigen still induced a large amount of IgG. In contrast to systemic responses, a fimbria-specific secretory IgA response was strongly induced by co-administration of rCTB and 0.5 microg fimbriae; the same amount of the antigen alone scarcely induced a response. Histopathological examination revealed IgA-positive plasma cells in the nasal mucosal tissue but no observable mast cells in the area. In addition, nasal administration of the fimbrial vaccine significantly protected the mice from P. gingivalis-mediated alveolar bone loss.

CONCLUSION

Nasal vaccination with a combination of fimbriae and rCTB can be an effective means of preventing P. gingivalis-mediated periodontitis.

摘要

引言

成人牙周炎由牙龈卟啉单胞菌等特定牙周病原体引发;然而,尚未确立预防该疾病的有效措施。在本研究中,使用BALB/c小鼠评估了由牙龈卟啉单胞菌菌毛和重组霍乱毒素B亚单位(rCTB)组成的疫苗的有效性。

方法

在第0、14、21和28天经鼻向BALB/c小鼠联合给予菌毛和rCTB。在第35天,处死小鼠,通过酶联免疫吸附测定法测定血清、唾液、鼻腔和肺提取物中的免疫球蛋白水平。通过测量牙槽骨丧失来评估该疫苗对小鼠牙龈卟啉单胞菌诱导的牙周炎的预防效果。

结果

当给小鼠施用微量(0.5微克)菌毛抗原时,rCTB显著提高了血清免疫球蛋白(Ig)A水平。对血清IgG产生的佐剂作用不明显,因为微量抗原仍诱导产生大量IgG。与全身反应相反,rCTB与0.5微克菌毛联合施用强烈诱导了菌毛特异性分泌型IgA反应;单独相同量的抗原几乎不诱导反应。组织病理学检查显示鼻黏膜组织中有IgA阳性浆细胞,但该区域未观察到肥大细胞。此外,经鼻施用菌毛疫苗可显著保护小鼠免受牙龈卟啉单胞菌介导的牙槽骨丧失。

结论

经鼻接种菌毛和rCTB的组合可能是预防牙龈卟啉单胞菌介导的牙周炎的有效手段。

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