用来自RgpA-Kgp蛋白酶-黏附素复合物的重组黏附素进行疫苗接种可预防牙龈卟啉单胞菌感染。
Vaccination with recombinant adhesins from the RgpA-Kgp proteinase-adhesin complex protects against Porphyromonas gingivalis infection.
作者信息
Frazer Leanne T, O'Brien-Simpson Neil M, Slakeski Nada, Walsh Katrina A, Veith Paul D, Chen Chao Guang, Barr Ian G, Reynolds Eric C
机构信息
Cooperative Research Centre for Oral Health Science, School of Dental Science, The University of Melbourne, 720 Swanston Street, Victoria 3010, Australia.
出版信息
Vaccine. 2006 Oct 30;24(42-43):6542-54. doi: 10.1016/j.vaccine.2006.06.013. Epub 2006 Jun 23.
Porphyromonas gingivalis is a pathogen associated with chronic periodontitis, an inflammatory disease of the supporting tissues of the teeth. A major virulence factor for P. gingivalis is the RgpA-Kgp proteinase-adhesin complex. We have prepared the following recombinant proteins corresponding to domains/regions of the RgpA-Kgp complex; rRgpA(cat), rRgpA(A1), rRgpA(A2), rRgpA(A4), rRgpA(A1)(784-1009), rRgpA(A1)(911-1009), rKgp(A1) and rKgp(A1)(759-989). The ability of each recombinant protein to attenuate P. gingivalis infection, when used as a vaccine, in the murine lesion model was determined. All of the recombinant adhesin domains were found to significantly attenuate P. gingivalis infection with the most effective being rKgp(A1) and rKgp(A1)(759-989) followed by rRgpA(A1), rRgpA(A1)(784-1009) and rRgpA(A1)(911-1009). The predominant antibody isotype was IgG1. The A1 adhesins, which gave the best protection, contain specific motifs implicated in binding to host tissue. Immunisation with rRgpA(cat) had no effect on P. gingivalis infection. As well as detecting the Kgp(A1) adhesin in a Western blot, the rKgp(A1) and rKgp(A1)(759-989) antisera were also immunoreactive with the A1 and A3 adhesins of RgpA and HagA. Flow cytometric analysis indicated that rKgp(A1) and rRgpA(A1) antisera recognised native antigen on P. gingivalis whole cells. Furthermore, the rKgp(A1) and rKgp(A1)(759-989) antisera exhibited a similar immunoreactive profile with outer membrane preparations of all P. gingivalis serotypes and clinical isolates tested. The recombinant A1 adhesin therefore has potential in the development of a P. gingivalis vaccine.
牙龈卟啉单胞菌是一种与慢性牙周炎相关的病原体,慢性牙周炎是一种牙齿支持组织的炎症性疾病。牙龈卟啉单胞菌的一个主要毒力因子是RgpA-Kgp蛋白酶-粘附素复合物。我们制备了以下与RgpA-Kgp复合物的结构域/区域相对应的重组蛋白;rRgpA(cat)、rRgpA(A1)、rRgpA(A2)、rRgpA(A4)、rRgpA(A1)(784-1009)、rRgpA(A1)(911-1009)、rKgp(A1)和rKgp(A1)(759-989)。测定了每种重组蛋白作为疫苗在小鼠损伤模型中减轻牙龈卟啉单胞菌感染的能力。发现所有重组粘附素结构域均能显著减轻牙龈卟啉单胞菌感染,其中最有效的是rKgp(A1)和rKgp(A1)(759-989),其次是rRgpA(A1)、rRgpA(A1)(784-1009)和rRgpA(A1)(911-1009)。主要的抗体亚型是IgG1。提供最佳保护的A1粘附素含有与宿主组织结合相关的特定基序。用rRgpA(cat)免疫对牙龈卟啉单胞菌感染没有影响。除了在蛋白质印迹中检测Kgp(A1)粘附素外,rKgp(A1)和rKgp(A1)(759-989)抗血清还与RgpA的A1和A3粘附素以及HagA发生免疫反应。流式细胞术分析表明,rKgp(A1)和rRgpA(A1)抗血清可识别牙龈卟啉单胞菌全细胞上的天然抗原。此外,rKgp(A1)和rKgp(A1)(759-989)抗血清对所有测试的牙龈卟啉单胞菌血清型和临床分离株的外膜制剂表现出相似的免疫反应谱。因此,重组A1粘附素在牙龈卟啉单胞菌疫苗的开发中具有潜力。