Spunde Karina, Korotkaja Ksenija, Sominskaya Irina, Zajakina Anna
Cancer Gene Therapy Group, Latvian Biomedical Research and Study Centre, Ratsupites Str. 1 k. 1, LV-1067 Riga, Latvia.
Mol Ther Nucleic Acids. 2025 Apr 8;36(2):102536. doi: 10.1016/j.omtn.2025.102536. eCollection 2025 Jun 10.
The COVID-19 pandemic underscored the urgency of developing effective vaccines to combat infectious diseases, especially in vulnerable populations such as the elderly and immunocompromised. While recombinant protein vaccines offer safety, their poor immunogenicity highlights the need for advanced vaccination platforms. New genetic/nucleic acid vaccine formulations like plasmid DNA and mRNA showed efficiency and safety in preclinical and clinical studies; however, they demand innovative adjuvants because their mechanism of action differs from traditional protein vaccines. Genetic adjuvants-encoded by nucleic acids within DNA, RNA, or viral vectors-emerge as a promising solution by targeting and modulating specific immune pathways, including antigen presentation, T cell activation, and memory formation. These innovative adjuvants enhance vaccine efficacy by fine-tuning innate and adaptive immune responses, overcoming immune senescence, and addressing the challenges of CD8 T cell activation in immunocompromised populations. This review explores the potential of genetically encoded adjuvants, including cytokines, chemokines, and other immune modulators. By comparing these adjuvants to traditional formulations, we highlight their capacity to address the limitations of modern vaccines while discussing their integration with emerging technologies like RNA-based vaccines. As genetic adjuvants advance toward clinical application, understanding their mechanisms and optimizing their delivery is pivotal to unlocking next-generation immunization strategies.
新冠疫情凸显了研发有效疫苗以对抗传染病的紧迫性，尤其是在老年人和免疫功能低下等弱势群体中。虽然重组蛋白疫苗具有安全性，但其较差的免疫原性凸显了先进疫苗平台的必要性。新型基因/核酸疫苗制剂，如质粒DNA和mRNA，在临床前和临床研究中显示出有效性和安全性；然而，由于其作用机制与传统蛋白疫苗不同，它们需要创新的佐剂。由DNA、RNA或病毒载体中的核酸编码的基因佐剂，通过靶向和调节特定免疫途径，包括抗原呈递、T细胞活化和记忆形成，成为一种有前景的解决方案。这些创新佐剂通过微调先天性和适应性免疫反应、克服免疫衰老以及解决免疫功能低下人群中CD8 T细胞活化的挑战，来提高疫苗效力。本综述探讨了基因编码佐剂的潜力，包括细胞因子、趋化因子和其他免疫调节剂。通过将这些佐剂与传统制剂进行比较，我们强调了它们解决现代疫苗局限性的能力，同时讨论了它们与基于RNA的疫苗等新兴技术的整合。随着基因佐剂向临床应用迈进，了解其作用机制并优化其递送对于解锁下一代免疫策略至关重要。
