Pathogenic Biology Institute, University of South China, Hengyang, People's Republic of China.
Can J Microbiol. 2012 Feb;58(2):117-23. doi: 10.1139/w11-115. Epub 2012 Jan 19.
In the present study, immunomodulatory responses of a DNA vaccine constructed by fusing Treponema pallidum (Tp) glycerophosphodiester phosphodiesterase (Gpd) to interleukin-2 (IL-2) and using chitosan (CS) nanoparticles as vectors were investigated. New Zealand white rabbits were immunized by intramuscular inoculation of control DNAs, Tp Gpd DNA vaccine, or Gpd-IL-2 fusion DNA vaccine, which were vectored by CS nanoparticles. Levels of the anti-Gpd antibodies and levels of IL-2 and interferon-γ in rabbits were increased upon inoculation of Gpd-IL-2 fusion DNA vaccine, when compared with the inoculation with Gpd DNA vaccine, with CS vectoring increasing the effects. The Gpd-IL-2 fusion DNA vaccine efficiently enhanced the antigen-specific lymphocyte proliferative response. When the rabbits were challenged intradermally with 10(5) Tp (Nichols) spirochetes, the Gpd-IL-2 fusion DNA vaccine conferred better protection than the Gpd DNA vaccine (P < 0.05), as characterized by lower detectable amounts of dark field positive lesions (17.5%), lower ulcerative lesion scores (15%), and faster recovery. Individuals treated with the Tp Gpd-IL-2 fusion DNA vaccine vectored by CS nanoparticles had the lowest amounts of dark field positive lesions (10%) and ulcerations (5%) observed and the fastest recovery (42 days). These results indicate that the Gpd-IL-2 fusion DNA vaccine vectored by CS nanoparticles can efficiently induce Th1-dominant immune responses, improve protective efficacy against Tp spirochete infection, and effectively attenuate development of syphilitic lesions.
在本研究中，我们研究了将梅毒螺旋体（Tp）甘油磷酸二酯磷酸二酯酶（Gpd）与白细胞介素-2（IL-2）融合构建的 DNA 疫苗的免疫调节反应，并使用壳聚糖（CS）纳米粒子作为载体。通过肌肉内接种对照 DNA、Tp Gpd DNA 疫苗或 Gpd-IL-2 融合 DNA 疫苗，用 CS 纳米粒子作为载体对新西兰白兔进行免疫接种。与接种 Gpd DNA 疫苗相比，接种 Gpd-IL-2 融合 DNA 疫苗可增加抗 Gpd 抗体水平和兔体内 IL-2 和干扰素-γ水平，CS 载体可增强这些效果。Gpd-IL-2 融合 DNA 疫苗可有效增强抗原特异性淋巴细胞增殖反应。当用 10(5)Tp（Nichols）螺旋体对兔子进行皮内攻击时，Gpd-IL-2 融合 DNA 疫苗比 Gpd DNA 疫苗提供更好的保护作用（P < 0.05），表现为可检测到的暗视野阳性病变数量更少（17.5%），溃疡性病变评分更低（15%），恢复更快。用 CS 纳米粒子载体的 Tp Gpd-IL-2 融合 DNA 疫苗治疗的个体观察到的暗视野阳性病变（10%）和溃疡（5%）数量最低，恢复最快（42 天）。这些结果表明，用 CS 纳米粒子载体的 Gpd-IL-2 融合 DNA 疫苗可有效诱导 Th1 优势免疫反应，提高对 Tp 螺旋体感染的保护效果，并有效减轻梅毒病变的发展。
