Pathogenic Biology Institute, School of Medicine, University of South China, Hengyang 421001, China.
Sci China Life Sci. 2013 Feb;56(2):174-80. doi: 10.1007/s11427-012-4434-4. Epub 2013 Jan 18.
Syphilis is a multistage, sexually transmitted disease caused by the spirochete, Treponema pallidum (Tp). A significantly high incidence of syphilis has been reported in several countries, including China, and there is an urgent need for the development of efficacious vaccines against syphilis. DNA vaccines are a major breakthrough in the field of vaccination with several advantages over traditional vaccines. Animal model studies of Tp DNA vaccines have not been reported elsewhere but our previous reports describe the development of a single-gene Tp DNA vaccine and preclinical immunization study. In this study, chitosan (CS) nanoparticles were used as a vector and an interleukin-2 expression plasmid (pIL-2) as an adjuvant to enhance a TpGpd DNA vaccine candidate (pTpGpd) in a rabbit Tp skin challenge model. At week 8 after the first immunization, three rabbits from each group were used to determine cytokine measurements and spleen lymphocyte proliferation assay. pTpGpd in combination with pIL-2 wrapped with CS led to the greatest enhancement of anti-TpGpd antibodies and T-cell proliferation. During infection, levels of anti-TpGpd antibodies and T-cell proliferation were measured. Both the serum special IgG and IL-2, interferon-γ were significantly increased by the co-injection of the IL-2 plasmid compared with the injection of TpGpd DNA alone (P<0.05). Furthermore, IL-2 plasmid coinjection efficiently enhanced the antigen-specific lymphocyte proliferation response. Additionally, the ratios of positive skin lesions and ulcer lesions in groups immunized with pTpGpd were significantly lower than those of the pIL-2, CS or pIL-2 mixed with CS control groups (P<0.001). CS vectored and pIL-2 adjuvanted pTpGpd immunized animals exhibited the lowest rates of positive skin tests (8.33%) and ulcer lesions (4.17%) and the fastest recovery (42 d). These experiments indicate that co-injection of a pIL-2 plasmid with pTpGpd DNA vaccine wrapped with CS can significantly strengthen the long-term stability of immune response during infection, efficiently improve the protective effect against T. pallidum spirochetes infection and attenuate syphilitic lesion development.
梅毒是一种由梅毒螺旋体（Tp）引起的多阶段性性传播疾病。包括中国在内的多个国家都报告了梅毒的发病率显著升高，因此迫切需要开发有效的梅毒疫苗。DNA 疫苗是疫苗领域的重大突破，与传统疫苗相比具有多项优势。动物模型研究中尚未报道 Tp DNA 疫苗，但我们之前的报告描述了一种单基因 Tp DNA 疫苗的开发和临床前免疫研究。在这项研究中，壳聚糖（CS）纳米粒子被用作载体，白细胞介素-2 表达质粒（pIL-2）作为佐剂，以增强兔 Tp 皮肤挑战模型中的 TpGpd DNA 疫苗候选物（pTpGpd）。在第一次免疫后第 8 周，每组 3 只兔子用于确定细胞因子测量和脾淋巴细胞增殖测定。pTpGpd 与包裹 CS 的 pIL-2 联合使用导致抗 TpGpd 抗体和 T 细胞增殖的最大增强。在感染期间，测量了抗 TpGpd 抗体和 T 细胞增殖的水平。与单独注射 TpGpd DNA 相比，共注射 IL-2 质粒可显著增加血清特异性 IgG 和 IL-2、干扰素-γ（P<0.05）。此外，IL-2 质粒共注射可有效增强抗原特异性淋巴细胞增殖反应。此外，与 pIL-2、CS 或 pIL-2 混合 CS 对照组相比，免疫接种 pTpGpd 的各组的阳性皮肤病变和溃疡病变的比例显著降低（P<0.001）。CS 载体和 pIL-2 佐剂 pTpGpd 免疫的动物表现出最低的阳性皮肤试验（8.33%）和溃疡病变（4.17%）以及最快的恢复（42 天）。这些实验表明，与 pTpGpd DNA 疫苗包裹的 CS 一起共注射 pIL-2 质粒可以显著增强感染期间免疫反应的长期稳定性，有效提高对梅毒螺旋体感染的保护作用，并减轻梅毒病变的发展。
