三tlr激动剂佐剂灭活新城疫病毒疫苗可促进鸡的Th1/Th2免疫应答，并具有一定的保护作用。

IF 4.5 3区医学 Q2 IMMUNOLOGY

Vaccine Pub Date : 2025-10-11 DOI:10.1016/j.vaccine.2025.127846

Abinaya Kaliappan , Saravanan Ramakrishnan , Khushboo Panwar , Dumala Naveen , Prasad Thomas , Surya Kant Verma , Mithilesh Singh , Vikash Chandra , Sohini Dey , Madhan Mohan Chellappa

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引用次数: 0

摘要

人们正在探索toll样受体（TLR）激动剂的组合，以减轻全身毒性并实现持久的理想免疫反应。在本研究中，我们研究了三tlr激动剂组合（LPS, TLR4; R-848， TLR7和CpG-ODN， TLR21）作为灭活新城疫病毒（NDV）疫苗的佐剂在鸡体内的应用。采用三联激动剂联合刺激鸡外周血单个核细胞（PBMCs），定量PCR分析免疫相关基因表达，评估免疫反应动力学。此外，在注射了三种TLR激动剂的鸟类脾脏样本中进行了转录组学分析。在免疫研究中，对禽类单独接种灭活NDV疫苗或与不同TLR激动剂混合物（单一、双重或三重）联合接种，然后评估体液和细胞免疫反应以及对攻击的保护。免疫应答研究结果显示，IL-1β、IFN-γ、IL-4、IFN-β、iNOS和MHC-II转录物显著上调，表明三联TLR激动剂联合使用具有促炎、抗病毒和混合Th1/Th2反应。转录组学分析显示，在促炎、抗炎和抗病毒反应等三tlr激动剂信号通路中，19个与免疫功能相关的差异表达基因（DEGs）显著上调。此外，免疫研究表明，低剂量的三tlr激动剂组合没有毒性，并显着增强体液和细胞介导的免疫反应，导致更高的抗体滴度，增加T细胞活化，并完全保护免受致命的NDV攻击。这些发现表明，三tlr激动剂联合使用可以提高疫苗效力，并为疫苗配方提供了一种具有成本效益的方法。

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Triple-TLR agonists' adjuvanted inactivated Newcastle disease virus vaccine promotes effective Th1/Th2 immune responses and affords protective efficacy in chickens

Combinations of Toll-like receptor (TLR) agonists are being explored to alleviate systemic toxicity and achieve long-lasting desirable immune responses. In this study, we investigated the use of a triple-TLR agonists' combination (LPS, TLR4; R-848, TLR7 and CpG-ODN, TLR21) as an adjuvant with the inactivated Newcastle disease virus (NDV) vaccine in chickens. We assessed the immune response kinetics by stimulating chicken peripheral blood mononuclear cells (PBMCs) with the triple agonist combination and analyzing immune-related gene expression using quantitative PCR. Additionally, transcriptomic analysis was performed in spleen samples from birds injected with the triple TLR agonists. In the immunization study, birds were vaccinated with an inactivated NDV vaccine alone or in combination with different TLR agonist mixtures (single, dual, or triple), followed by assessment of both humoral and cellular immune responses and protection against challenge. Results from immune response study showed significant upregulation of IL-1β, IFN-γ, IL-4, IFN-β, iNOS and MHC-II transcripts, indicating the pro-inflammatory, anti-viral and mixed Th1/Th2 responses in triple TLR agonists' combination. Transcriptomic analysis revealed significant upregulation of 19 differentially expressed genes (DEGs) related to immune function in triple-TLR agonists signaling pathway such as pro-inflammatory, anti-inflammatory and anti-viral response. Furthermore, the immunization study demonstrated that the triple-TLR agonist combination, at a low dose exhibited no toxicity and significantly enhanced both humoral and cell-mediated immune responses, leading to higher antibody titres, increased T cell activation, and complete protection against a virulent NDV challenge. These findings suggest that the triple-TLR agonists' combination could improve vaccine efficacy and provide a cost-effective approach for vaccine formulations.

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来源期刊

Vaccine 医学-免疫学

CiteScore

8.70

自引率

5.50%

发文量

992

审稿时长

131 days

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