Moradi Jale, Izad Maryam, Tabrizi Mina, Mosavari Nader, Esmaeili Behnaz, Feizabadi Mohammad Mehdi
1 Department of Microbiology, School of Medicine, Tehran University of Medical Sciences , Tehran, Iran.
2 Department of Immunology, School of Medicine, Tehran University of Medical Sciences , Tehran, Iran.
Acta Microbiol Immunol Hung. 2018 Jun 1;65(2):193-209. doi: 10.1556/030.65.2018.019. Epub 2018 Mar 19.
One third of the world population are latently infected with Mycobacterium tuberculosis and are at the risk of reactivation of tuberculosis (TB). The most effective strategy for control of TB worldwide is the development of a vaccine that inhibits progression of latent TB to active infection. In this study, two optimized constructs consisting of multi-epitopes DNA derived from three latency antigens Rv2029c, Rv2031c, and Rv2627c fused with or without light chain 3 (LC3) are synthetized. The immunogenicity effectiveness of two DNA constructs was evaluated in the mouse model. LC3-fused multi-epitope DNA construct induced strong specific Th1 immune responses with high increase in IFN-γ CD4 and IL-2 CD4 T cell populations (both with p < 0.0001) and IFN-γ IL-2 CD4 T cell population (p < 0.0001) compared with empty vector, BCG, and multi-epitope DNA construct groups. The LC3-fused construct induced IFN-γ CD8 T cell population (p < 0.0001) compared with empty vector and BCG groups but could not induce the T cell population compared with construct without LC3. Importantly, LC3-fused DNA construct did not induce epitope-specific IL-4 and IL-10 from CD4 and CD8 T cell populations. The results indicated that LC3-fused multi-epitope DNA construct has a potential to be investigated for future development of a new TB vaccine.
世界三分之一的人口潜伏感染结核分枝杆菌，有结核病（TB）复发的风险。全球控制结核病最有效的策略是研发一种能抑制潜伏性结核进展为活动性感染的疫苗。在本研究中，合成了两种优化构建体，由源自三种潜伏抗原Rv2029c、Rv2031c和Rv2627c的多表位DNA组成，分别融合或未融合轻链3（LC3）。在小鼠模型中评估了两种DNA构建体的免疫原性效果。与空载体、卡介苗和多表位DNA构建体组相比，融合LC3的多表位DNA构建体诱导了强烈的特异性Th1免疫反应，IFN-γ CD4和IL-2 CD4 T细胞群体（两者p < 0.0001）以及IFN-γ IL-2 CD4 T细胞群体（p < 0.0001）显著增加。与空载体和卡介苗组相比，融合LC3的构建体诱导了IFN-γ CD8 T细胞群体（p < 0.0001），但与未融合LC3的构建体相比，未能诱导T细胞群体。重要的是，融合LC3的DNA构建体未从CD4和CD8 T细胞群体中诱导出表位特异性IL-4和IL-10。结果表明，融合LC3的多表位DNA构建体有潜力用于未来新型结核病疫苗的研发研究。
