Jiang Fan, Peng Cong, Cheng Peng, Wang Jie, Lian Jianqi, Gong Wenping
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 100091, China.
The Second Brigade of Cadet, Basic Medical Science Academy of Air Force Medical University, Xi'an 710032, China.
Vaccines (Basel). 2023 Apr 17;11(4):856. doi: 10.3390/vaccines11040856.
Latent tuberculosis infection (LTBI) is the primary source of active tuberculosis (ATB), but a preventive vaccine against LTBI is lacking. In this study, dominant helper T lymphocyte (HTL), cytotoxic T lymphocyte (CTL), and B-cell epitopes were identified from nine antigens related to LTBI and regions of difference (RDs). These epitopes were used to construct a novel multiepitope vaccine (MEV) based on their antigenicity, immunogenicity, sensitization, and toxicity. The immunological characteristics of the MEV were analyzed with immunoinformatics technology and verified by enzyme-linked immunospot assay and Th1/Th2/Th17 cytokine assay in vitro. A novel MEV, designated PP19128R, containing 19 HTL epitopes, 12 CTL epitopes, 8 B-cell epitopes, toll-like receptor (TLR) agonists, and helper peptides, was successfully constructed. Bioinformatics analysis showed that the antigenicity, immunogenicity, and solubility of PP19128R were 0.8067, 9.29811, and 0.900675, respectively. The global population coverage of PP19128R in HLA class I and II alleles reached 82.24% and 93.71%, respectively. The binding energies of the PP19128R-TLR2 and PP19128R-TLR4 complexes were -1324.77 kcal/mol and -1278 kcal/mol, respectively. In vitro experiments showed that the PP19128R vaccine significantly increased the number of interferon gamma-positive (IFN-γ) T lymphocytes and the levels of cytokines, such as IFN-γ, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and IL-10. Furthermore, positive correlations were observed between PP19128R-specific cytokines in ATB patients and individuals with LTBI. The PP19128R vaccine is a promising MEV with excellent antigenicity and immunogenicity and no toxicity or sensitization that can induce robust immune responses in silico and in vitro. This study provides a vaccine candidate for the prevention of LTBI in the future.
潜伏性结核感染（LTBI）是活动性结核病（ATB）的主要来源，但目前缺乏针对LTBI的预防性疫苗。在本研究中，从与LTBI相关的9种抗原和差异区域（RDs）中鉴定出主要辅助性T淋巴细胞（HTL）、细胞毒性T淋巴细胞（CTL）和B细胞表位。基于这些表位的抗原性、免疫原性、致敏性和毒性，构建了一种新型多表位疫苗（MEV）。利用免疫信息学技术分析了MEV的免疫学特性，并通过酶联免疫斑点试验和体外Th1/Th2/Th17细胞因子试验进行了验证。成功构建了一种名为PP19128R的新型MEV，它包含19个HTL表位、12个CTL表位、8个B细胞表位、Toll样受体（TLR）激动剂和辅助肽。生物信息学分析表明，PP19128R的抗原性、免疫原性和溶解度分别为0.8067、9.29811和0.900675。PP19128R在HLA I类和II类等位基因中的全球人群覆盖率分别达到82.24%和93.71%。PP19128R-TLR2和PP19128R-TLR4复合物的结合能分别为-1324.77千卡/摩尔和-1278千卡/摩尔。体外实验表明，PP19128R疫苗显著增加了干扰素γ阳性（IFN-γ）T淋巴细胞的数量以及IFN-γ、肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）和IL-10等细胞因子的水平。此外，在ATB患者和LTBI个体中观察到PP19128R特异性细胞因子之间存在正相关。PP19128R疫苗是一种有前景的MEV，具有优异的抗原性和免疫原性，无毒性或致敏性，可在计算机模拟和体外诱导强烈的免疫反应。本研究为未来预防LTBI提供了一种候选疫苗。
