Clinical Research Department, Pasteur Institute of Iran, Tehran, Iran.
Hepatitis, AIDS and Blood borne diseases Department, Pasteur Institute of Iran, Tehran, Iran.
Curr Drug Deliv. 2021;18(7):1014-1021. doi: 10.2174/1567201818666210101113601.
There have been massive efforts on vaccine development against HIV-1 since its discovery. Various approaches have been taken to attention, including rational vaccine design, optimized delivery systems and heterologous regimen to eradicate the virus. DNA vaccines fundamentally induce host immune responses by genetically engineered plasmids encoding antigens and expressed in vivo without the need of the specific delivery system. Therefore, long-term endogenous antigen expression could be possible.
In this study, we aimed at evaluation and comparison of DNA and protein vaccine based on two forms of full and truncated HIV-1 p24-nef antigens by in silico design in BLALB/c.
The recombinant pcDNA3.1 harboring two sets of HIV-1 p24 and nef genes in truncated and full forms were generated and applied to immunize BALB/c along with the corresponding proteins via three different DNA/DNA, DNA/protein and protein/protein regimens.
The results showed that the applied regimens could elicit strong immune responses in comparison with controls and the prim-boost DNA/protein regimen reached the highest immune induction (p < 0.05). Moreover, prime-boost approach was assessed more successfully in a qualitatively broad Th1 response induction. The truncated form of the antigens, p24(80-231 aa)-AAY- Nef (120-150), was evaluated more immunogenic in agreement with the in silico investigation.
The truncated form of p24-Nef was evaluated highly immunogenic specially when applied in prim-boost DNA/Protein regimen and could be investigated in other delivery systems and a proper animal model to achieve a therapeutic vaccine candidate against HIV-1.
自 HIV-1 发现以来，人们已经在疫苗开发方面做出了巨大努力。人们采取了各种方法来关注它，包括合理的疫苗设计、优化的传递系统和异源方案来消灭病毒。DNA 疫苗通过遗传工程质粒在体内表达编码抗原，从根本上诱导宿主免疫反应，而不需要特定的传递系统。因此，长期的内源性抗原表达是可能的。
在这项研究中，我们旨在通过计算机设计，评估和比较基于两种形式的全长和截短的 HIV-1 p24-nef 抗原的 DNA 和蛋白质疫苗在 BLALB/c 中的效果。
生成了携带两套 HIV-1 p24 和 nef 基因的截短和全长形式的重组 pcDNA3.1，并通过三种不同的 DNA/DNA、DNA/蛋白质和蛋白质/蛋白质方案将其与相应的蛋白质一起用于免疫 BALB/c。
结果表明，与对照组相比，所应用的方案可以引起强烈的免疫反应，而 DNA/蛋白质的初免-加强方案达到了最高的免疫诱导（p < 0.05）。此外，初免-加强方法在定性上更成功地诱导了广泛的 Th1 反应。与计算机研究一致，抗原的截短形式，p24（80-231 aa）-AAY-Nef（120-150），被评估为更具免疫原性。
截短形式的 p24-Nef 被评估为高度免疫原性，特别是在初免-加强 DNA/蛋白质方案中应用时，并且可以在其他传递系统和适当的动物模型中进行研究，以获得针对 HIV-1 的治疗性疫苗候选物。
