Pellegrina Diogo, Wilson Heather L, Mutwiri George K, Helmy Mohamed
Vaccine and Infectious Diseases Organization (VIDO), University of Saskatchewan, Saskatoon, SK S7N 5A2, Canada.
Vaccinology and Immunotherapeutics Program, School of Public Health, University of Saskatchewan, Saskatoon, SK S7N 5A2, Canada.
Vaccines (Basel). 2025 Jan 1;13(1):33. doi: 10.3390/vaccines13010033.
Adjuvants are a diverse group of substances that can be added to vaccines to enhance antigen-specific immune responses and improve vaccine efficacy. The first adjuvants, discovered almost a century ago, were soluble crystals of aluminium salts. Over the following decades, oil emulsions, vesicles, oligodeoxynucleotides, viral capsids, and other complex organic structures have been shown to have adjuvant potential. However, the detailed mechanisms of how adjuvants enhance immune responses remain poorly understood and may be a barrier that reduces the rational selection of vaccine components. Previous studies on mechanisms of action of adjuvants have focused on how they activate innate immune responses, including the regulation of cell recruitment and activation, cytokine/chemokine production, and the regulation of some "immune" genes. This approach provides a narrow perspective on the complex events involved in how adjuvants modulate antigen-specific immune responses. A comprehensive and efficient way to investigate the molecular mechanism of action for adjuvants is to utilize systems biology approaches such as transcriptomics in so-called "systems vaccinology" analysis. While other molecular biology methods can verify if one or few genes are differentially regulated in response to vaccination, systems vaccinology provides a more comprehensive picture by simultaneously identifying the hundreds or thousands of genes that interact with complex networks in response to a vaccine. Transcriptomics tools such as RNA sequencing (RNA-Seq) allow us to simultaneously quantify the expression of practically all expressed genes, making it possible to make inferences that are only possible when considering the system as a whole. Here, we review some of the challenges in adjuvant studies, such as predicting adjuvant activity and toxicity when administered alone or in combination with antigens, or classifying adjuvants in groups with similar properties, while underscoring the significance of transcriptomics in systems vaccinology approaches to propel vaccine development forward.
佐剂是一类多样的物质，可添加到疫苗中以增强抗原特异性免疫反应并提高疫苗效力。近一个世纪前发现的首批佐剂是铝盐的可溶性晶体。在随后的几十年里，油乳剂、囊泡、寡脱氧核苷酸、病毒衣壳和其他复杂有机结构已被证明具有佐剂潜力。然而，佐剂增强免疫反应的详细机制仍知之甚少，这可能是阻碍合理选择疫苗成分的一个因素。先前关于佐剂作用机制的研究主要集中在它们如何激活先天免疫反应，包括细胞募集和激活的调节、细胞因子/趋化因子的产生以及一些“免疫”基因的调节。这种方法对于佐剂如何调节抗原特异性免疫反应所涉及的复杂事件提供了一个狭隘的视角。研究佐剂作用分子机制的一种全面而有效的方法是在所谓的“系统疫苗学”分析中利用转录组学等系统生物学方法。虽然其他分子生物学方法可以验证一个或几个基因在接种疫苗后是否受到差异调节，但系统疫苗学通过同时识别响应疫苗与复杂网络相互作用的数百或数千个基因提供了更全面的情况。诸如RNA测序（RNA-Seq）之类的转录组学工具使我们能够同时量化几乎所有已表达基因的表达，从而能够做出只有在将系统作为一个整体考虑时才可能得出的推断。在此，我们回顾佐剂研究中的一些挑战，例如预测单独使用或与抗原联合使用时的佐剂活性和毒性，或将佐剂分类为具有相似特性的组，同时强调转录组学在推动疫苗开发的系统疫苗学方法中的重要性。
