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编码传染性法氏囊病VP2基因和结核分枝杆菌截短型HSP70的DNA疫苗构建体对鸡的保护效力

Protective efficacy of a DNA vaccine construct encoding the VP2 gene of infectious bursal disease and a truncated HSP70 of Mycobacterium tuberculosis in chickens.

作者信息

Maity Hemanta Kumar, Dey Sohini, Mohan C Madhan, Khulape Sagar A, Pathak Dinesh C, Vakharia Vikram N

机构信息

Recombinant DNA Lab, Division of Veterinary Biotechnology, Indian Veterinary Research Institute, Izatnagar, Bareilly 243 122, India.

Recombinant DNA Lab, Division of Veterinary Biotechnology, Indian Veterinary Research Institute, Izatnagar, Bareilly 243 122, India.

出版信息

Vaccine. 2015 Feb 18;33(8):1033-9. doi: 10.1016/j.vaccine.2015.01.006. Epub 2015 Jan 14.

Abstract

Infectious bursal disease (IBD) is an acute, infectious, immunosuppressive disease affecting young chicken worldwide. The etiological agent IBD virus (IBDV) is a double stranded RNA virus with outer capsid protein VP2 of IBDV is the major antigenic determinant capable of inducing neutralizing antibody. DNA vaccines encoding VP2 has been extensively studied achieving only partial protection. However, the efficacy of DNA vaccines against IBDV can be augmented by choosing a potential molecular adjuvant. The goal of the present study is to evaluate the immune response and protective efficacy of a DNA vaccine encoding the C-terminal domain of the heat shock protein 70 (cHSP70) of Mycobacterium tuberculosis gene genetically fused with the full length VP2 gene of IBDV (pCIVP2-cHSP70) in comparison to a 'DNA prime-protein boost' approach and a DNA vaccine encoding the VP2 gene (pCIVP2) alone. The results indicate that both pCIVP2-cHSP70 and 'DNA prime-protein boost' elicited humoral as well as cellular immune responses. Chickens in the pCIVP2-cHSP70 and 'DNA prime-protein boost' groups developed significantly higher levels of ELISA titer to IBDV antigen compared to the group immunized with pCIVP2 alone (p<0.01). However, significantly higher levels of lymphocyte proliferative response, IL-12 and IFN-γ production were found in the pCIVP2-cHSP70 group compared to 'DNA prime-protein boost' group. Additionally, chickens immunized with pCIVP2-cHSP70 and 'DNA prime-protein boost' vaccines were completely protected against the vvIBDV whereas pCIVP2 DNA vaccine alone was able to protect only 70%. These findings suggest that the truncated C-terminal HSP70 mediated DNA vaccine genetically fused with the VP2 gene construct stimulated both humoral and cell mediated immune responses and conferred complete protection against IBDV. This novel strategy is perhaps a seminal concept in utilizing HSP70 as an adjuvant molecule to elicit an immune response against IBD affecting chickens.

摘要

传染性法氏囊病(IBD)是一种影响全球幼鸡的急性、传染性、免疫抑制性疾病。病原体IBD病毒(IBDV)是一种双链RNA病毒,IBDV的外膜蛋白VP2是能够诱导中和抗体的主要抗原决定簇。编码VP2的DNA疫苗已被广泛研究,但仅能提供部分保护。然而,通过选择一种潜在的分子佐剂可以增强DNA疫苗对IBDV的效力。本研究的目的是评估与“DNA初免-蛋白加强”方法以及单独编码VP2基因的DNA疫苗(pCIVP2)相比,编码结核分枝杆菌热休克蛋白70(cHSP70)的C末端结构域与IBDV全长VP2基因遗传融合的DNA疫苗(pCIVP2-cHSP70)的免疫反应和保护效力。结果表明,pCIVP2-cHSP70和“DNA初免-蛋白加强”均引发了体液免疫和细胞免疫反应。与单独用pCIVP2免疫的组相比,pCIVP2-cHSP70组和“DNA初免-蛋白加强”组的鸡对IBDV抗原产生的ELISA效价显著更高(p<0.01)。然而,与“DNA初免-蛋白加强”组相比,pCIVP2-cHSP70组的淋巴细胞增殖反应、IL-12和IFN-γ产生水平显著更高。此外,用pCIVP2-cHSP70和“DNA初免-蛋白加强”疫苗免疫的鸡对vvIBDV完全具有保护作用,而单独的pCIVP2 DNA疫苗仅能保护70%。这些发现表明,与VP2基因构建体遗传融合的截短C末端HSP70介导的DNA疫苗刺激了体液免疫和细胞介导的免疫反应,并对IBDV提供了完全保护。这种新策略可能是利用HSP70作为佐剂分子引发针对影响鸡的IBD的免疫反应的一个开创性概念。

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