Shen Yanru, Huang Weijin, Nie Jianhui, Zhang Li
Division of HIV/AIDS and Sex-Transmitted Virus Vaccines, Institute for Biological Product Control, National Institutes for Food and Drug Control (NIFDC), Beijing 102629, China.
WHO Collaborating Center for Standardization and Evaluation of Biologicals, Beijing 102629, China.
Vaccines (Basel). 2025 Mar 31;13(4):371. doi: 10.3390/vaccines13040371.
Low antigen immunogenicity poses a significant challenge in vaccine development, often leading to inadequate immune responses and reduced vaccine efficacy. Therefore, the discovery of potent immune-enhancing adjuvants is crucial. STING (stimulator of interferon genes) agonists are a promising class of adjuvants which have been identified in various immune cells and are activated in response to DNA fragments, triggering a broad range of type-I interferon-dependent immune responses. Integrating STING agonists with vaccine components is an ideal strategy to bolster vaccine-induced immunity to infections and cancer cells. Several STING agonists are currently under investigation in preclinical studies and clinical trials; however, some have shown limited efficacy, while others exhibit off-target effects. To ensure safety, they are typically delivered with carriers that exhibit high biocompatibility and insolubility. In this review, we present the latest research on natural and synthetic STING agonists that have been effectively used in vaccine development, and summarize their application in adjuvant preventive and therapeutic vaccines. Additionally, we discuss the safety of STING agonists as vaccine adjuvants by reviewing potential delivery strategies. Overall, incorporating STING agonists into vaccine formulations represents a significant advancement in vaccine research with the potential to significantly enhance immune responses and improve vaccine efficacy. However, ongoing research is still required to identify the most effective and safe delivery strategies for STING agonists, as well as to evaluate their long-term safety and efficacy in clinical trials.
低抗原免疫原性在疫苗开发中构成了重大挑战，常常导致免疫反应不足和疫苗效力降低。因此，发现有效的免疫增强佐剂至关重要。干扰素基因刺激因子（STING）激动剂是一类很有前景的佐剂，已在各种免疫细胞中被鉴定出来，并在对DNA片段作出反应时被激活，引发广泛的I型干扰素依赖性免疫反应。将STING激动剂与疫苗成分整合是增强疫苗诱导的抗感染和癌细胞免疫力的理想策略。目前有几种STING激动剂正在临床前研究和临床试验中进行研究；然而，一些已显示出有限的效力，而另一些则表现出脱靶效应。为确保安全性，它们通常与具有高生物相容性和不溶性的载体一起递送。在本综述中，我们介绍了已有效用于疫苗开发的天然和合成STING激动剂的最新研究，并总结了它们在佐剂预防性和治疗性疫苗中的应用。此外，我们通过回顾潜在的递送策略来讨论STING激动剂作为疫苗佐剂的安全性。总体而言，将STING激动剂纳入疫苗制剂代表了疫苗研究的一项重大进展，有可能显著增强免疫反应并提高疫苗效力。然而，仍需要进行持续研究，以确定STING激动剂最有效和安全的递送策略，并评估它们在临床试验中的长期安全性和效力。
