Umar Muhammad, Afzal Haroon, Murtaza Asad, Cheng Li-Ting
Graduate Institute of Animal Vaccine Technology, College of Veterinary Medicine, National Pingtung University of Science and Technology, Pingtung 91201, Taiwan.
International Program in Animal Vaccine Technology, International College, National Pingtung University of Science and Technology, Pingtung 91201, Taiwan.
Vaccines (Basel). 2025 Jan 2;13(1):36. doi: 10.3390/vaccines13010036.
Toll-like receptor 2 (TLR2) signaling is a pivotal component of immune system activation, and it is closely linked to the lipidation of bacterial proteins. This lipidation is guided by bacterial signal peptides (SPs), which ensure the precise targeting and membrane anchoring of these proteins. The lipidation process is essential for TLR2 recognition and the activation of robust immune responses, positioning lipidated bacterial proteins as potent immunomodulators and adjuvants for vaccines against bacterial-, viral-, and cancer-related antigens. The structural diversity and cleavage pathways of bacterial SPs are critical in determining lipidation efficiency and protein localization, influencing their immunogenic potential. Recent advances in bioinformatics have significantly improved the prediction of SP structures and cleavage sites, facilitating the rational design of recombinant lipoproteins optimized for immune activation. Moreover, the use of SP-containing lipobox motifs, as adjuvants to lipidate heterologous proteins, has expanded the potential of vaccines targeting a broad range of pathogens. However, challenges persist in expressing lipidated proteins, particularly within heterologous systems. These challenges can be addressed by optimizing expression systems, such as engineering strains for enhanced lipidation. Thus, lipoprotein signal peptides (SPs) demonstrate remarkable versatility as adjuvants in vaccine development, diagnostics, and immune therapeutics, highlighting their essential role in advancing immune-based strategies to combat diverse pathogens.
Toll样受体2（TLR2）信号传导是免疫系统激活的关键组成部分，它与细菌蛋白的脂化密切相关。这种脂化由细菌信号肽（SP）引导，这些信号肽确保这些蛋白的精确靶向和膜锚定。脂化过程对于TLR2识别和强大免疫反应的激活至关重要，使脂化细菌蛋白成为针对细菌、病毒和癌症相关抗原的疫苗的有效免疫调节剂和佐剂。细菌SP的结构多样性和切割途径对于确定脂化效率和蛋白定位至关重要，影响它们的免疫原性潜力。生物信息学的最新进展显著提高了对SP结构和切割位点的预测，有助于合理设计针对免疫激活进行优化的重组脂蛋白。此外，使用含SP的脂盒基序作为使异源蛋白脂化的佐剂，扩大了针对多种病原体的疫苗的潜力。然而，在表达脂化蛋白方面，尤其是在异源系统中，挑战仍然存在。这些挑战可以通过优化表达系统来解决，例如工程改造菌株以增强脂化。因此，脂蛋白信号肽（SP）在疫苗开发、诊断和免疫治疗中作为佐剂表现出显著的多功能性，突出了它们在推进基于免疫的策略以对抗多种病原体方面的重要作用。
