Evaluation of Brucella abortus DNA vaccine by expression of Cu-Zn superoxide dismutase antigen fused to IL-2
Evaluation of Brucella abortus DNA vaccine by expression of Cu-Zn superoxide dismutase antigen fused to IL-2
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DOI：
10.1016/j.imbio.2005.09.004
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发表时间：
2006-01-01
期刊：
影响因子：
2.8
通讯作者：
Oñate, A
中科院分区：
文献类型：
--
作者：
González-Smith, A;Vemulapalli, R;Oñate, A
牛种布氏杆菌的铜锌超氧化物歧化酶（SOD）抗原先前被鉴定为T细胞抗原，其诱导来自感染小鼠的T细胞的增殖和γ干扰素（IFN-γ）分泌。在早期的研究中，我们证明了肌肉注射携带SOD基因的质粒DNA的小鼠导致对B的显着保护的发展。流产攻毒。据报道，由DNA疫苗产生的抗原特异性免疫应答可以通过某些细胞因子基因的共递送来增强。在这项研究中，我们评估的效果，提供IL-2的SOD DNA疫苗的效力，通过产生质粒（pSecTagSOD-IL-2），编码的分泌型融合蛋白的SOD和IL-2。另一种质粒（pSecTag-SOD）仅编码作为分泌蛋白的SOD，用于比较。BALB/c小鼠肌肉注射pSecTag-SOD或pSecTag-SOD-IL 2，产生SOD特异性抗体和T细胞免疫应答。重组SOD（rSOD）抗原体外刺激后，pSecTag-SOD-IL 2免疫小鼠的T细胞增殖反应低于pSecTag-SOD免疫小鼠，但产生的IFN-γ浓度明显高于pSecTag-SOD免疫小鼠。然而，两种DNA疫苗诱导相似水平的SOD特异性抗体和细胞毒性T细胞应答。虽然pSecTag-SOD-IL 2免疫小鼠对B攻击的抵抗力增强。牛流产杆菌强毒株2308，这种增加与pSecTag-SOD接种的小鼠相比没有统计学显著性。这些结果表明，与IL 2融合的SOD DNA疫苗没有提高保护效力。(c)2005年Elsevier GmbH。All rights reserved.
The Cu-Zn superoxide dismutase (SOD) antigen of Brucella abortus was previously identified to be a T cell antigen which induces both proliferation of and gamma interferon (IFN-gamma) secretion by T cells from infected mice. In an earlier study, we demonstrated that intramuscular injection of mice with a plasmid DNA carrying the gene for SOD leads to the development of significant protection against B. abortus challenge. It has been reported that the antigen-specific immune responses generated by a DNA vaccine can be enhanced by co-delivery of certain cytokine genes. In this study, we evaluated the effect of delivering IL-2 on the efficacy of SOD DNA vaccine by generating a plasmid (pSecTagSOD-IL2) that codes for a secretory fusion protein of SOD and IL-2. Another plasmid (pSecTag-SOD) that codes for only SOD as a secretory protein was used for comparison. BALB/c mice injected intramuscularly with pSecTag-SOD or pSecTag-SOD-IL2, but not the control plasmid pSecTag, developed SOD-specific antibody and T cell immune responses. Upon in vitro stimulation with recombinant SOD (rSOD) antigen, T cells from mice immunized with pSecTag-SOD-IL2, in comparison with those from mice immunized with pSecTag-SOD, exhibited a lower proliferation response but produced significantly higher concentrations of IFN-gamma. Both DNA vaccines, however, induced similar levels of SOD-specific antibodies and cytotoxic T cell response. Although mice immunized with pSecTag-SOD-IL2 showed increased resistance to challenge with B. abortus virulent strain 2308, this increase was not statistically significant from that of pSecTag-SOD vaccinated mice. These results suggest that a SOD DNA vaccine fused to IL2 did not improve protection efficacy. (c) 2005 Elsevier GmbH. All rights reserved.