Vaccination of mice with a cocktail DNA vaccine induces a Th1-type immune response and partial protection against Schistosoma japonicum infection.
Vaccination of mice with a cocktail DNA vaccine induces a Th1-type immune response and partial protection against Schistosoma japonicum infection.
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DOI：
10.1016/s0264-410x(01)00420-0
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发表时间：
2001-12
期刊：
影响因子：
5.5
通讯作者：
Yaobi Zhang;M. Taylor;M. Johansen;Q. Bickle
中科院分区：
文献类型：
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作者：
Yaobi Zhang;M. Taylor;M. Johansen;Q. Bickle
几种已确定的日本血吸虫疫苗候选抗原在大型动物疫苗接种实验中显示出良好的前景。然而，在实验室用单个重组抗原或编码单个抗原的DNA免疫小鼠，尽管产生了特异性抗体，但从减虫率来看，迄今未能诱导对日本血吸虫尾蚴攻击感染的显著保护。这与使用具有高度保护性的辐射减毒疫苗所取得的结果形成了鲜明对比。即使在大型动物疫苗接种实验中，使用单一确定的抗原获得的保护水平也远远低于使用减毒疫苗获得的保护水平。一种可能的解释是，单一抗原接种诱导的免疫反应可能不足以对抗具有挑战性的感染。因此，我们使用了一种鸡尾酒DNA疫苗进行了小鼠免疫实验，该DNA疫苗由四个编码四种不同日本血吸虫抗原的DNA质粒组成，分别为Sj62、Sj28、Sj23和Sj14-3-3。我们还研究了与鸡尾酒DNA疫苗共注射小鼠IL-12编码质粒是否能够增强Th1反应，从而增强保护性免疫。三次肌肉注射鸡尾酒DNA疫苗后，在重组抗原的体外刺激下，脾细胞产生高水平的干扰素-γ，从而诱导了显著的Th1型细胞反应。重要的是，对粗线虫抗原也有显著的免疫球蛋白G抗体反应。在三个实验中，有两个显示出显著的抵抗力(分别为34-37%和44-45%)，而另一个实验没有显示出对日本血吸虫尾蚴攻击感染的任何保护作用。与单独注射鸡尾酒DNA相比，联合注射编码IL-12的DNA并没有进一步增强这些反应，也没有进一步增强耐药性水平。
Several defined vaccine candidate antigens of Schistosoma japonicum have shown promise in large animal vaccination experiments. However, vaccination of mice in the laboratory with either single recombinant antigens or DNA encoding forms of the individual antigens has so far failed to induce significant protection against S. japonicum cercarial challenge infection as judged by worm reduction, although specific antibodies were generated. This is in contrast to the results achieved using radiation-attenuated vaccines which are highly protective. Even in large animal vaccination experiments, the protection levels obtained with single defined antigens were far below those achieved using the attenuated vaccines. One possible interpretation is that the immune responses induced by single antigen vaccination may not be strong enough to combat the challenging infection. We, therefore, carried out mouse vaccination experiments using a cocktail DNA vaccine comprising four DNA plasmids encoding four different S. japonicum antigens, Sj62, Sj28, Sj23 and Sj14-3-3, respectively. We, also investigated whether co-injection of the mouse IL-12 encoding plasmid with the cocktail DNA vaccine was able to enhance the Th1 responses and hence the protective immunity. Three intramuscular injections of the cocktail DNA vaccine induced a significant Th1-type cellular response with high level of IFN-γ production by splenocytes upon in vitro stimulation with recombinant antigens. Importantly, significant IgG antibody responses were also induced against crude worm antigens. In two out of three experiments, significant resistance (34–37 and 44–45%, respectively) was demonstrated while another experiment did not show any protection against S. japonicum cercarial challenge infection. Co-injection of the IL-12 encoding DNA did not further enhance these responses, nor the level of resistance, compared with the cocktail DNA alone.