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评价咪喹莫特和 CpG ODN 1826 佐剂在嵌合 DNA 疫苗中的辅助作用对日本脑炎的影响。

Evaluation of the adjuvant effect of imiquimod and CpG ODN 1826 in chimeric DNA vaccine against Japanese encephalitis.

机构信息

Department of Infectious Disease, Shengjing Hospital of China Medical University, Shenyang 110004, China.

Department of Gastroenterology, Wuhan Red Cross Hospital, Wuhan 430015, China.

出版信息

Int Immunopharmacol. 2024 Oct 25;140:112816. doi: 10.1016/j.intimp.2024.112816. Epub 2024 Jul 30.

Abstract

Vaccines represent a significant milestone in the history of human medical science and serve as the primary means for controlling infectious diseases. In recent years, the geographical distribution of Japanese encephalitis viruses (JEV) of various genotypes has become increasingly complex, which provides a rationale for the development of safer and more effective vaccines. The advent of subunit and nucleic acid vaccines, especially propelled by advancements in genetic engineering since the 1980s, has accelerated the application of novel adjuvants. These novel vaccine adjuvants have diversified into toll-like receptor (TLR) agonists, complex adjuvants, nanoparticles and so on. However, the efficacy of adjuvant combinations can vary depending on the host system, disease model, or vaccine formulation, sometimes resulting in competitive or counteractive effects. In our previous study, we constructed a pJME-LC3 chimeric DNA vaccine aimed at inducing an immune response through autophagy induction. Building on this, we investigated the impact of the TLR7/8 agonist imiquimod (IMQ) and the TLR9 agonist CpG ODN 1826 as adjuvants on the immunogenicity of the Japanese encephalitis chimeric DNA vaccine. Our findings indicate that the combination of the pJME-LC3 vaccine with IMQ and CpG ODN 1826 adjuvants enhanced the innate immune response, promoting the maturation and activation of antigen-presenting cells in the early immune response. Furthermore, it played a regulatory and optimizing role in subsequent antigen-specific immune responses, resulting in effective cellular and humoral immunity and providing prolonged immune protection. The synergistic effect of IMQ and CpG ODN 1826 as adjuvants offers a novel approach for the development of Japanese encephalitis nucleic acid vaccines.

摘要

疫苗是人类医学科学史上的一个重要里程碑,是控制传染病的主要手段。近年来,各种基因型的日本脑炎病毒(JEV)的地理分布变得越来越复杂,这为开发更安全、更有效的疫苗提供了依据。自 20 世纪 80 年代以来,随着基因工程技术的进步,亚单位疫苗和核酸疫苗的出现加速了新型佐剂的应用。这些新型疫苗佐剂已经多样化为 Toll 样受体(TLR)激动剂、复合佐剂、纳米颗粒等。然而,佐剂组合的功效可能因宿主系统、疾病模型或疫苗配方而异,有时会产生竞争或拮抗作用。在我们之前的研究中,我们构建了一种 pJME-LC3 嵌合 DNA 疫苗,旨在通过诱导自噬来诱导免疫反应。在此基础上,我们研究了 TLR7/8 激动剂咪喹莫特(IMQ)和 TLR9 激动剂 CpG ODN 1826 作为佐剂对日本脑炎嵌合 DNA 疫苗免疫原性的影响。我们的研究结果表明,pJME-LC3 疫苗与 IMQ 和 CpG ODN 1826 佐剂联合使用增强了先天免疫反应,促进了抗原呈递细胞在早期免疫反应中的成熟和激活。此外,它在随后的抗原特异性免疫反应中发挥了调节和优化作用,导致有效的细胞和体液免疫,并提供了持久的免疫保护。IMQ 和 CpG ODN 1826 作为佐剂的协同作用为日本脑炎核酸疫苗的开发提供了一种新方法。

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