Zhao Feijun, Wu Yimou, Zhang Xiaohong, Yu Jian, Gu Weiming, Liu Shuangquan, Zeng Tiebing, Zhang Yuejun, Wang Shiping
Department of Parasitology, Xiangya School of Medicine, Central South University, Changsha, China.
Hum Vaccin. 2011 Oct;7(10):1083-9. doi: 10.4161/hv.7.10.16541. Epub 2011 Oct 1.
In this study, the immune-modulatory and protective efficacy of using an interleukin-2 (IL-2) expression plasmid as a genetic adjuvant and chitosan (CS) nanoparticles as vectors to enhance a Tp92 DNA vaccine candidate were investigated in a Treponema pallidum (Tp) rabbit challenge model.
CS vectoring of pTp92 or pIL-2 were both demonstrated to augment anti-Tp92 antibody levels induced by pTp92 DNA vaccines. Interestingly, the combination of CS vectored Tp92 and pIL-2 led to the greatest enhancements of anti-Tp92 antibodies and T-cell proliferation (p < 0.05). At week 10 after the first immunization, 15 of the 18 rabbits in each group were challenged with Tp Nichols strain and monitored for skin lesions and ulcer lesions. Ratios of positive skin lesions and ratios of ulcer lesions in groups immunized with pTp92 were significantly lower than those of the empty vector or PBS groups (p < 0.05), demonstrating that pTp92 immunization elicited significant protective efficacy against the Tp Nichols strain challenge. CS vectored and pIL-2 adjuvanted pTp92 immunized animals exhibited the lowest rates of positive skin and ulcer lesions.
Male New Zealand white rabbits were randomly assigned to groups (n = 18/group) and immunized intramuscularly with pTp92 based plasmid DNA constructs (100 μg of DNA/rabbit/immunization). Two weeks before Tp challenge (Week 8), three rabbits from each group were used to determine cytokine measurements and fifteen rabbits from each group were used for Tp challenge studies.
Intramuscular injection of pTp92 induced strong humoral and cellular immune responses and conferred protection from Tp challenge in rabbits. The use of CS as a pTp92 vector or pIL-2 as an adjuvant achieved a superior level of protective efficacy against Tp challenge, however CS vectored, IL-2 adjuvanted pTp92 immunization conferred the highest level of protective efficacy.
在本研究中，在梅毒螺旋体（Tp）兔攻击模型中，研究了使用白细胞介素-2（IL-2）表达质粒作为基因佐剂以及壳聚糖（CS）纳米颗粒作为载体来增强一种Tp92 DNA候选疫苗的免疫调节和保护效果。
pTp92或pIL-2的CS载体均被证明可增强pTp92 DNA疫苗诱导的抗Tp92抗体水平。有趣的是，CS载体化的Tp92与pIL-2的组合导致抗Tp92抗体和T细胞增殖的增强最为显著（p<0.05）。首次免疫后第10周，每组18只兔子中的15只接受Tp Nichols菌株攻击，并监测皮肤病变和溃疡病变。用pTp92免疫的组中阳性皮肤病变比例和溃疡病变比例显著低于空载体组或PBS组（p<0.05），表明pTp92免疫对Tp Nichols菌株攻击引发了显著的保护效果。CS载体化且pIL-2佐剂化的pTp92免疫动物表现出最低的阳性皮肤和溃疡病变率。
将雄性新西兰白兔随机分组（每组n = 18），肌肉注射基于pTp92的质粒DNA构建体（每只兔子每次免疫100μg DNA）。在Tp攻击前两周（第8周），每组三只兔子用于测定细胞因子水平，每组15只兔子用于Tp攻击研究。
肌肉注射pTp92可诱导强烈的体液和细胞免疫反应，并使兔子免受Tp攻击。使用CS作为pTp92载体或pIL-2作为佐剂对Tp攻击具有更高水平的保护效果，然而CS载体化、IL-2佐剂化的pTp92免疫具有最高水平的保护效果。
