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Development of a novel chimeric PA-LF antigen of Bacillus anthracis, its immunological characterization and evaluation as a future vaccine candidate in mouse model.
Biologicals ( IF 1.5 ) Pub Date : 2019-08-13 , DOI: 10.1016/j.biologicals.2019.07.004
Anshul Varshney 1 , Manoj Kumar 1 , D P Nagar 1 , Vijai Pal 1 , A K Goel 1
Affiliation  

Tremendous efforts are being made to develop an anthrax vaccine with long term protection. The main component of traditional anthrax vaccine is protective antigen (PA) with the trace amount of other proteins and bacterial components. In this study, we developed a recombinant PA-LF chimera antigen of Bacillus anthracis by fusing the PA domain 2-4 with lethal factor (LF) domain 1 and evaluated its protective potential against B. anthracis in mouse model. The anti-PA-LF chimera serum reacted with both PA and LF antigen, individually. The chimera elicited a strong antibody titer in mice with predominance of IgG1 isotype followed by IgG2b, IgG2a and IgG3. Cytokines were assessed in splenocytes of immunized mice and a significant up-regulation in the expression of IL-4, IL-10, IFN-γ and TNF-α was observed. The PA-LF chimera immunized mice exhibited 80% survival after challenge with virulent spores of B. anthracis. Pathological studies showed normal architecture in vital organs (spleen, lung, liver and kidney) of recovered immunized mice on 20 DPI after spore challenge. These findings suggested that PA-LF chimera of B. anthracis elicited good humoral as well as cell mediated immune response in mice, and thus, can be a potent vaccine candidate against anthrax.



中文翻译:

炭疽芽孢杆菌新型嵌合PA-LF抗原的开发,免疫学特性和评估,可作为未来小鼠模型中的候选疫苗。

人们正在做出巨大的努力来开发具有长期保护作用的炭疽疫苗。传统炭疽疫苗的主要成分是保护性抗原(PA),还有痕量的其他蛋白质和细菌成分。在这项研究中,我们通过将PA结构域2-4与致命因子(LF)结构域1融合,开发了炭疽芽孢杆菌的重组PA-LF嵌合抗原,并评估了其对炭疽芽孢杆菌的保护潜力在鼠标模型中。抗PA-LF嵌合体血清分别与PA和LF抗原反应。嵌合体在以IgG1同种型,接着是IgG2b,IgG2a和IgG3为主的小鼠中引起了很强的抗体效价。在免疫小鼠的脾细胞中评估细胞因子,并且观察到IL-4,IL-10,IFN-γ和TNF-α的表达显着上调。在用炭疽芽孢杆菌的强力孢子攻击后,PA-LF嵌合体免疫小鼠表现出80%的存活率病理学研究显示,经孢子激发后20 DPI,恢复的免疫小鼠的重要器官(脾,肺,肝和肾)的正常结构。这些发现提示炭疽芽孢杆菌的PA-LF嵌合体 在小鼠中引起了良好的体液免疫以及细胞介导的免疫反应,因此可以作为抗炭疽的有效疫苗候选者。

更新日期:2019-08-13
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