Atta Ur Rahman School of Applied Biosciences, National University of Sciences and Technology, Islamabad, Pakistan.
German Cancer Research Center (DFKZ), German Cancer Research Consortium (DKTK), Heidelberg, Germany.
BMC Genomics. 2023 May 24;24(1):276. doi: 10.1186/s12864-023-09330-4.
Despite being in the 21 century, the world has still not been able to vanquish the global AIDS epidemic, and the only foreseeable solution seems to be a safe and effective vaccine. Unfortunately, vaccine trials so far have returned unfruitful results, possibly due to their inability to induce effective cellular, humoral and innate immune responses. The current study aims to tackle these limitations and propose the desired vaccine utilizing immunoinformatic approaches that have returned promising results in designing vaccines against various rapidly mutating organisms. For this, all polyprotein and protein sequences of HIV-1 were retrieved from the LANL (Los Alamos National Laboratory) database. The consensus sequence was generated after alignment and used to predict epitopes. Conserved, antigenic, non-allergenic, T-cell inducing, B-cell inducing, IFN-ɣ inducing, non-human homologous epitopes were selected and combined to propose two vaccine constructs i.e., HIV-1a (without adjuvant) and HIV-1b (with adjuvant).
HIV-1a and HIV-1b were subjected to antigenicity, allergenicity, structural quality analysis, immune simulations, and MD (molecular dynamics) simulations. Both proposed multi-epitope vaccines were found to be antigenic, non-allergenic, stable, and induce cellular, humoral, and innate immune responses. TLR-3 docking and in-silico cloning of both constructs were also performed.
Our results indicate HIV-1b to be more promising than HIV-1a; experimental validations can confirm the efficacy and safety of both constructs and in-vivo efficacy in animal models.
尽管我们已经进入 21 世纪,但全球艾滋病疫情仍未得到有效控制,目前看来,唯一可行的解决方案似乎是研发一种安全有效的疫苗。然而,迄今为止,疫苗试验并未取得成功,其原因可能在于这些疫苗无法诱导有效的细胞、体液和固有免疫应答。本研究旨在克服这些局限性,利用免疫信息学方法设计出一种理想的疫苗,该方法在设计针对各种快速突变生物体的疫苗方面已取得了良好的效果。为此,我们从 LANL(洛斯阿拉莫斯国家实验室)数据库中检索了所有 HIV-1 的多蛋白和蛋白序列。经过比对后,生成了共识序列,用于预测抗原表位。选择保守的、抗原性的、非变应原性的、T 细胞诱导的、B 细胞诱导的、IFN-ɣ 诱导的、非人类同源性的表位,并将其组合起来,提出了两种疫苗构建体,即 HIV-1a(无佐剂)和 HIV-1b(有佐剂)。
我们对 HIV-1a 和 HIV-1b 进行了抗原性、变应原性、结构质量分析、免疫模拟和 MD(分子动力学)模拟。结果表明,这两种多表位疫苗均具有抗原性、非变应原性、稳定性,并能诱导细胞、体液和固有免疫应答。还进行了 TLR-3 对接和两种构建体的计算机模拟克隆。
我们的研究结果表明,HIV-1b 比 HIV-1a 更有前途;实验验证可以确认这两种构建体的有效性和安全性,以及在动物模型中的体内疗效。