Barazani Osnat, Erdos Thomas, Chowdhury Raafi, Kaur Gursimratpreet, Venketaraman Vishwanath
College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, CA 91766, USA.
Department of Biology, University of California, Riverside, CA 9252, USA.
Biology (Basel). 2025 Apr 13;14(4):417. doi: 10.3390/biology14040417.
(Mtb) vaccines are designed to prevent infection, prevent reactivation of latent infection, and/or provide adjuvant therapy to standard TB treatment for active Mtb. Emerging vaccine technologies include reverse vaccinology, DNA and RNA vaccines, subunit vaccines, and multi-epitope vaccines. Currently, many different types of vaccine candidates are in clinical trials, though, to date, BCG remains the only approved Mtb vaccine. Mtb has a complex genome with numerous antigens, but not all are equally effective in eliciting immunity, so a critical challenge is the selection of antigens and epitopes that are most likely to induce a long-term, broad-spectrum protective immune response. Multi-epitope vaccines (MEVs) represent a new event horizon in vaccine development. Bioinformatic computer modeling is being used to maximize efficacy and minimalize adverse effects. Although no multi-epitope vaccines have proceeded to in vivo clinical trials, three candidate MEVs have made it through in silico tests. Multi-epitope vaccine candidate PP13138R, containing 13 HTL epitopes, 13 CTL epitopes, and 8 B cell epitopes in addition to both TLR2 and TLR4 agonists, aims to elicit a broad immune response that could address both active and latent Mtb infection. Similarly, immunoinformatic data were used to design and validate another MEV candidate based on the biomarker PE_PGRS17 with four B cell, nine HTL, and six CTL linked epitopes, with a griselimycin sequence as the adjuvant. A third novel prophylactic and therapeutic MEV was developed that targets Ag85A, AG85B, ESAT-6, and CFP-10 proteins with 12 CTL, 25 HTL, and 21 LBL epitopes with a CpG adjuvant.
结核分枝杆菌（Mtb）疫苗旨在预防感染、防止潜伏感染的再激活，和/或为活动性Mtb的标准结核病治疗提供辅助治疗。新兴的疫苗技术包括反向疫苗学、DNA和RNA疫苗、亚单位疫苗以及多表位疫苗。目前，许多不同类型的候选疫苗正在进行临床试验，不过，迄今为止，卡介苗仍然是唯一获批的Mtb疫苗。Mtb具有复杂的基因组，包含众多抗原，但并非所有抗原在引发免疫方面都同样有效，因此一个关键挑战是选择最有可能诱导长期、广谱保护性免疫反应的抗原和表位。多表位疫苗（MEV）代表了疫苗开发的一个新领域。生物信息学计算机建模正被用于最大化疗效并最小化不良反应。尽管尚无多表位疫苗进入体内临床试验，但有三种候选MEV通过了计算机模拟测试。候选多表位疫苗PP13138R除了含有TLR2和TLR4激动剂外，还包含13个辅助性T淋巴细胞（HTL）表位、13个细胞毒性T淋巴细胞（CTL）表位和8个B细胞表位，旨在引发广泛的免疫反应，以应对活动性和潜伏性Mtb感染。同样，免疫信息学数据被用于设计和验证另一种基于生物标志物PE_PGRS17的MEV候选疫苗，该疫苗具有四个B细胞、九个HTL和六个CTL连接表位，并以griselinimycin序列作为佐剂。开发了第三种新型预防性和治疗性MEV，其靶向Ag85A、AG85B、ESAT-6和CFP-10蛋白，具有12个CTL、25个HTL和21个线性B淋巴细胞（LBL）表位，并以CpG作为佐剂。
