Maue Alexander C, Waters W Ray, Palmer Mitchell V, Nonnecke Brian J, Minion F Chris, Brown Wendy C, Norimine Junzo, Foote Monica R, Scherer Charles F C, Estes D Mark
Department of Molecular Microbiology and Immunology, University of Missouri, Columbia, MO 65211, USA.
Vaccine. 2007 Jun 11;25(24):4735-46. doi: 10.1016/j.vaccine.2007.03.052. Epub 2007 Apr 24.
The potency of genetic immunization observed in the mouse has demonstrated the utility of DNA vaccines to induce cell-mediated and humoral immune responses. However, it has been relatively difficult to generate comparable responses in non-rodent species. The use of molecular adjuvants may increase the magnitude of these suboptimal responses. In this study, we demonstrate that the co-administration of plasmid-encoded GM-CSF and CD80/CD86 with a novel ESAT-6:CFP10 DNA vaccine against bovine tuberculosis enhances antigen-specific cell-mediated immune responses. ESAT-6:CFP10+GM-CSF+CD80/CD86 DNA vaccinated animals exhibited significant (p<0.01) antigen-specific proliferative responses compared to other DNA vaccinates. Increased expression (p< or =0.05) of CD25 on PBMC from ESAT-6:CFP10+GM-CSF+CD80/CD86 DNA vaccinates was associated with increased proliferation, as compared to control DNA vaccinates. Significant (p<0.05) numbers of ESAT-6:CFP10-specific IFN-gamma producing cells were evident from all ESAT-6:CFP10 DNA vaccinated animals compared to control DNA vaccinates. However, the greatest increase in IFN-gamma producing cells was from animals vaccinated with ESAT-6:CFP10+GM-CSF+CD80/CD86 DNA. In a low-dose aerosol challenge trial, calves vaccinated as neonates with Mycobacterium bovis BCG and ESAT-6:CFP10+GM-CSF+CD80/CD86 DNA exhibited decreased lesion severity in the lung and lung-associated lymph nodes following viruluent M. bovis challenge compared to other vaccinated animals or non-vaccinated controls. These data suggest that a combined vaccine regimen of M. bovis BCG and a candidate ESAT-6:CFP10 DNA vaccine may offer greater protection against tuberculosis in cattle than vaccination with BCG alone.
在小鼠中观察到的基因免疫效力已证明DNA疫苗在诱导细胞介导免疫应答和体液免疫应答方面的效用。然而，在非啮齿动物物种中产生类似的应答相对困难。使用分子佐剂可能会增强这些次优应答的强度。在本研究中，我们证明，将质粒编码的GM-CSF和CD80/CD86与一种新型的抗牛结核病ESAT-6:CFP10 DNA疫苗共同给药，可增强抗原特异性细胞介导的免疫应答。与其他DNA疫苗接种动物相比，接种ESAT-6:CFP10+GM-CSF+CD80/CD86 DNA疫苗的动物表现出显著（p<0.01）的抗原特异性增殖应答。与对照DNA疫苗接种动物相比，ESAT-6:CFP10+GM-CSF+CD80/CD86 DNA疫苗接种动物的外周血单核细胞上CD25表达增加（p≤0.05），这与增殖增加相关。与对照DNA疫苗接种动物相比，所有接种ESAT-6:CFP10 DNA疫苗的动物中均明显存在大量（p<0.05）产生ESAT-6:CFP10特异性干扰素-γ的细胞。然而，产生干扰素-γ的细胞增加最多的是接种ESAT-6:CFP10+GM-CSF+CD80/CD86 DNA疫苗的动物。在一项低剂量气溶胶攻击试验中，与其他接种疫苗的动物或未接种疫苗的对照相比，新生时接种牛分枝杆菌卡介苗和ESAT-6:CFP10+GM-CSF+CD80/CD86 DNA疫苗的犊牛在受到强毒牛分枝杆菌攻击后，肺部和肺相关淋巴结的病变严重程度降低。这些数据表明，牛分枝杆菌卡介苗和候选ESAT-6:CFP10 DNA疫苗的联合疫苗接种方案可能比单独接种卡介苗能为牛提供更好的结核病防护。
