Abstract:

In recent years, bacterial infections have emerged as the second leading cause of death globally, posing a serious threat to public health and demanding prioritized intervention from the healthcare community worldwide. While antibiotics have conventionally been used as the primary strategy to combat bacterial infections, their efficacy is increasingly compromised due to the emergence of drug-resistant bacteria, especially multi-drug-resistant and even pan-drug-resistant superbacteria. Vaccines are thus considered as one of the most scientific, economical, safe, and effective means to prevent infectious diseases and improve public health, which are estimated to save 2 to 3 million lives annually, and can serve as a critical tool in the battle against antimicrobial resistance. However, the complexity of bacterial structure and pathogenic mechanism has hindered the development of vaccines. Challenges include screening and rationally design of effective antigens, ensuring compatibility of various antigen combinations, establishing animal models for preclinical evaluation, and defining reliable endpoints for clinical efficacy assessment. As a result, only a small number of bacteria vaccines have been successfully developed so far, and none of them has been licensed to combat the most prevalent drug-resistant infections, such as Staphylococcus aureus, Acinetobacter baumannii, Pseudomonas aeruginosa and Klebsiella pneumoniae. Synthetic biology is a brand-new multidisciplinary focusing on repurposing natural biological systems and inventing innovative biological tools, technologies, devices, and systems for practical applications, and its concepts, principles and technologies have been extensively employed to facilitate vaccine development, including rational design, screening, and optimization of antigen, carrier, adjuvant and delivery system as well as the modulation of bacterial pathogenicity and immune responses. Herein, we outline the current status of the development of bacterial vaccines and the advancement of clinical trials for drug-resistant bacterial vaccines. Then, we summarize the application of synthetic biology technology in the development of major bacterial vaccines. Finally, we prospect the potential of synthetic biology in creating novel bacterial vaccines. Researchers have access to a greater variety of design possibilities for bacterial vaccines through synthetic biology. To maximize these benefits, we should employ synthetic biology and related technologies more efficiently in developing bacterial vaccines. Meanwhile, we should develop a scientific, reasonable, effective, and feasible management system, as well as regulatory measures, to expedite the development of efficient bacterial vaccines, therefore addressing the problem of antibiotic resistance to protect human health. {L-End}

Key words: bacterial infection, antibiotic resistance, vaccines, synthetic biology

摘要：

细菌感染已成为全球第二大死亡因素，给人类健康与公共安全造成了巨大威胁。抗生素一直是治疗细菌感染最为主要的手段，但越来越严重的耐药问题给传统的抗生素疗法带来了严峻挑战。除了抗生素之外，疫苗被认为是防治传染性疾病传播最为科学、经济、安全和有效的手段，在人类抗击病原体感染斗争中发挥了重要作用。然而，细菌基因组庞大，致病机制复杂，研发疫苗存在有效抗原筛选、设计、制备难，抗原组合配伍难，有效性评价难，研发周期长等诸多瓶颈，导致细菌疫苗研发进展缓慢，尤其是临床常见的严重耐药致病菌尚无有效的疫苗可用。合成生物学是一门新兴的交叉学科，近年来在疫苗研究领域已经得到了广泛应用，包括抗原的筛选、理性设计、配伍组合，载体、佐剂和递送系统的设计以及免疫应答调控等。本文综述了细菌疫苗研究的现状以及耐药细菌疫苗临床试验研究进展，总结了合成生物学技术在几种重要类型细菌疫苗研发中的应用进展，最后对相关前景进行了展望。合成生物学在疫苗的形式、疫苗递送、疫苗的研制效率等方面为研究人员提供了更为广阔的空间，未来，应最大化地发挥合成生物学的优势，充分发展和应用合成生物学技术手段，建立科学、理性、有效、可行的管理制度，建设生物安全保障法律体系和监管措施，高效推动细菌疫苗研发，解决抗生素耐药问题，造福人类健康。

关键词: 细菌感染, 抗生素耐药, 疫苗, 合成生物学