在小鼠模型中使用两种内源性佐剂提高编码HIV-1 Nef抗原的DNA疫苗的效力。

Improving the potency of DNA vaccine encoding HIV-1 Nef antigen using two endogenous adjuvants in mouse model.

作者信息

Jafarzade B S, Sadat S M, Yaghobi R, Bolhassani A

出版信息

Bratisl Lek Listy. 2017;118(9):564-569. doi: 10.4149/BLL_2017_108.

DOI:10.4149/BLL_2017_108

PMID:29061065

Abstract

BACKGROUND

DNA immunization can induce long-term immune responses, which are required to design an effective HIV vaccine. It was shown that antigen-expressing plasmids can increase the protective immunity against infectious diseases such as: influenza and malaria. However, DNA-based immunizations have poor immunogenicity, thus the use of potent immunoadjuvants can enhance their potency.

METHODS

In the current study, preparation of the recombinant HIV-1 Nef, Gp96 and HMGB1 DNA constructs was performed in bacterial system. Then, the immunogenicity of DNA construct harboring HIV-1 Nef gene (pcDNA-Nef) was studied using two endogenous adjuvants (pcDNA-HMGB1 and pcDNA-Gp96) in BALB/c mouse model.

RESULTS

Our data showed that co-injection of pcDNA-Nef with pcDNA-HMGB1 effectively raised both humoral and cell-mediated immune responses in mice as compared to pcDNA-Nef adjuvanted with pcDNA-gp96. Indeed, co-immunization of HIV-1 Nef DNA with HMGB1 DNA significantly induced high levels of IgG2a and IFN-γ directed toward Th1 responses and also cytotoxic T lymphocytes (CTLs) activity in comparison with other immunized groups.

CONCLUSION

These findings suggest that the full length of HMGB1 gene could be a more efficient adjuvant for improvement of therapeutic HIV DNA-based immunization compared to the full length of gp96 gene (Tab. 1, Fig. 3, Ref. 58).

摘要

背景

DNA免疫可诱导长期免疫反应，这是设计有效的HIV疫苗所必需的。研究表明，表达抗原的质粒可增强针对诸如流感和疟疾等传染病的保护性免疫。然而，基于DNA的免疫原性较差，因此使用强效免疫佐剂可增强其效力。

方法

在本研究中，重组HIV-1 Nef、Gp96和HMGB1 DNA构建体在细菌系统中制备。然后，在BALB/c小鼠模型中，使用两种内源性佐剂（pcDNA-HMGB1和pcDNA-Gp96）研究携带HIV-1 Nef基因的DNA构建体（pcDNA-Nef）的免疫原性。

结果

我们的数据表明，与用pcDNA-gp96作为佐剂的pcDNA-Nef相比，pcDNA-Nef与pcDNA-HMGB1共同注射可有效提高小鼠的体液免疫和细胞介导的免疫反应。事实上，与其他免疫组相比，HIV-1 Nef DNA与HMGB1 DNA共同免疫显著诱导了高水平的针对Th1反应的IgG2a和IFN-γ，以及细胞毒性T淋巴细胞（CTLs）活性。