Antigen engineering can play a critical role in the protective immunity elicited by Yersinia pestis DNA vaccines.
Antigen engineering can play a critical role in the protective immunity elicited by Yersinia pestis DNA vaccines.
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抗原工程在鼠疫耶尔森氏菌 DNA 疫苗引发的保护性免疫中发挥着关键作用。
DOI：
10.1016/j.vaccine.2009.10.059
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发表时间：
2010
期刊：
影响因子：
5.5
通讯作者：
Lu,Shan
中科院分区：
文献类型：
--
作者：
Wang,Shixia;Mboudjeka,Innocent;Goguen,JonD;Lu,Shan
在以前报道的研究中，利用DNA免疫方法递送针对鼠疫耶尔森氏菌的保护性抗原已经取得了成功。在目前的研究中，V和F1这两种被充分研究的毒力因子作为疫苗开发的主要靶点，其基因设计被改变，以探索更多的选择，以期提高表达这两种抗原的DNA疫苗的保护性免疫。与野生型V基因DNA疫苗相比，使用密码子优化的V基因序列可有效提高抗原表达、抗V抗体反应滴度，并提高抗粘膜致死挑战的存活率。对于F1 DNA疫苗，去除n端疏水区能够提高保护性免疫。然而，在F1中加入哺乳动物信号肽序列实际上导致了保护作用的降低，尽管它诱导了稍高的抗F1抗体反应。F1基因可以与一个编码YscF（一种新证实的鼠疫杆菌部分保护性抗原）的基因融合，以生产表达融合F1和YscF抗原的DNA疫苗。其中一种设计，特别是将YscF融合到F1的下游序列，比单独的F1或YscF DNA疫苗产生更好的保护作用，这表明这两种抗原之间存在潜在的协同作用。上述研究结果表明，优化鼠疫DNA疫苗保护性免疫有多种途径。最重要的是，通过适当的抗原工程在DNA疫苗中产生最佳的抗原基因插入物，显然可以在未来设计各种DNA疫苗中发挥重要作用。
The use of a DNA immunization approach to deliver protective antigens against Yersinia pestis (Y. pestis) has been successful in previously reported studies. In the current study, the gene designs for V and F1, two well-studied virulent factors serving as main targets for vaccine development, were altered to explore additional options in hopes of improving the protective immunity of DNA vaccines expressing these two antigens. Compared to the wild type V gene DNA vaccines, the use of codon optimized V gene sequences was effective in improving the antigen expression, titers of anti-V antibody responses, and survival against a mucosal lethal challenge. For the F1 DNA vaccine, removal of the N-terminal hydrophobic region was able to improve protective immunity. However, adding a mammalian signal peptide sequence to F1 actually led to reduced protection despite it inducing slightly higher anti-F1 antibody responses. The F1 gene can be fused with a gene coding for YscF, a newly confirmed partial protective antigen for Y. pestis, to produce DNA vaccines that express fused F1 and YscF antigens. One design, in particular, that had YscF fused to the downstream sequence of F1, produced better protection than separate F1 or YscF DNA vaccines, suggesting a potential synergistic effect between these two antigens. Findings from the above studies indicated that there are multiple approaches to optimize the protective immunity for plague DNA vaccines. Most importantly, proper antigen engineering to produce optimal antigen gene inserts in DNA vaccines can clearly play a major role in the future designs of a wide range of DNA vaccines.