Tuberculosis Prevention and Control Key Laboratory/Beijing Key Laboratory of New Techniques of Tuberculosis Diagnosis and Treatment, Senior Department of Tuberculosis, The 8th Medical Center of PLA General Hospital, Beijing, China.
Hebei North University, Zhangjiakou, Hebei, China.
Front Cell Infect Microbiol. 2022 Nov 2;12:1047306. doi: 10.3389/fcimb.2022.1047306. eCollection 2022.
Our previous study developed a novel peptide-based vaccine, MP3RT, to fight against tuberculosis (TB) infection in a mouse model. However, the consistency between the immunoinformatics predictions and the results of real-world animal experiments on the MP3RT vaccine remains unclear.
In this study, we predicted the antigenicity, immunogenicity, physicochemical parameters, secondary structure, and tertiary structure of MP3RT using bioinformatics technologies. The immune response properties of the MP3RT vaccine were then predicted using the C-ImmSim server. Finally, humanized mice were used to verify the characteristics of the humoral and cellular immune responses induced by the MP3RT vaccine.
MP3RT is a non-toxic and non-allergenic vaccine with an antigenicity index of 0.88 and an immunogenicity index of 0.61, respectively. Our results showed that the MP3RT vaccine contained 53.36% α-helix in the secondary structure, and the favored region accounted for 98.22% in the optimized tertiary structure. The binding affinities of the MP3RT vaccine to the human leukocyte antigen (HLA)-DRB1*01:01 allele, toll-like receptor-2 (TLR-2), and TLR-4 receptors were -1234.1 kcal/mol, -1066.4 kcal/mol, and -1250.4 kcal/mol, respectively. The results of the C-ImmSim server showed that the MP3RT vaccine could stimulate T and B cells to produce immune responses, such as high levels of IgM and IgG antibodies, IFN-γ, TNF-α, and IL-2 cytokines. Results from real-world animal experiments showed that the MP3RT vaccine could stimulate the humanized mice to produce high levels of IgG and IgG2a antibodies and IFN-γ T lymphocytes. Furthermore, the levels of IFN-γ, IL-2, and IL-6 cytokines in mice immunized with the MP3RT vaccine were significantly higher than those in the control group.
MP3RT is a highly antigenic and immunogenic potential vaccine that can effectively induce Th1-type immune responses analysis and animal experiments. This study lays the foundation for evaluating the value of computational tools and immunoinformatic techniques in reverse vaccinology research.
我们之前的研究开发了一种新型基于肽的疫苗 MP3RT，以在小鼠模型中对抗结核（TB）感染。然而，MP3RT 疫苗的免疫信息学预测与真实世界动物实验结果之间的一致性尚不清楚。
在这项研究中，我们使用生物信息学技术预测了 MP3RT 的抗原性、免疫原性、理化参数、二级结构和三级结构。然后使用 C-ImmSim 服务器预测了 MP3RT 疫苗的免疫反应特性。最后，使用人源化小鼠验证了 MP3RT 疫苗诱导的体液和细胞免疫反应的特征。
MP3RT 是一种无毒、无过敏原的疫苗，其抗原指数为 0.88，免疫原性指数为 0.61。我们的结果表明，MP3RT 疫苗的二级结构中包含 53.36%的α-螺旋，优化后的三级结构中优先区域占 98.22%。MP3RT 疫苗与人类白细胞抗原（HLA）-DRB1*01:01 等位基因、Toll 样受体-2（TLR-2）和 TLR-4 受体的结合亲和力分别为-1234.1 kcal/mol、-1066.4 kcal/mol 和-1250.4 kcal/mol。C-ImmSim 服务器的结果表明，MP3RT 疫苗可以刺激 T 细胞和 B 细胞产生免疫反应，如高水平的 IgM 和 IgG 抗体、IFN-γ、TNF-α 和 IL-2 细胞因子。真实世界动物实验的结果表明，MP3RT 疫苗可以刺激人源化小鼠产生高水平的 IgG 和 IgG2a 抗体以及 IFN-γ T 淋巴细胞。此外，用 MP3RT 疫苗免疫的小鼠中 IFN-γ、IL-2 和 IL-6 细胞因子的水平明显高于对照组。
MP3RT 是一种具有高度抗原性和免疫原性潜力的疫苗，可有效诱导 Th1 型免疫反应。这项研究为评估计算工具和免疫信息学技术在反向疫苗学研究中的价值奠定了基础。
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