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评价 Pam2CSK4、poly（I:C）和咪喹莫特不同组合对树突状细胞和鸭体内 H9N2 禽流感抗原免疫反应的增强作用。

Evaluation of different combination of pam2CSK4, poly (I:C) and imiquimod enhance immune responses to H9N2 avian influenza antigen in dendritic cells and duck.

机构信息

College of Veterinary Medicine, Henan University of Animal Husbandry and Economy, Zhengzhou, Henan, China.

Huannong (Zhaoqing) Institute of Biotechnology Co. Ltd., Zhaoqing, Guangdong, China.

出版信息

PLoS One. 2022 Jul 19;17(7):e0271746. doi: 10.1371/journal.pone.0271746. eCollection 2022.

DOI:10.1371/journal.pone.0271746
PMID:35853030
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9295992/
Abstract

Current commercial H9 avian influenza viruses (AIVs) vaccines cannot provide satisfactory antibody titers and protective immunity against AIVs in duck. Toll like receptors (TLR) ligand as AIVs adjuvants can activate dendritic cells to improve immune responses in multiple animals, while the studies were absent in duck. Therefore, we investigated TLR ligands pam2CSK4, poly (I:C) and/or imiquimod enhance immune responses to inactivated H9N2 avian influenza antigen (H9N2 IAIV) in peripheral blood monocyte-derived dendritic cells (MoDCs) and duck. In vitro, we observed that transcription factor NF-κB, Th1/Th2 type cytokines (IFN-γ, IL-2 and IL-6) and the ability of catching H9N2 IAIV antigen were significantly up-regulated when H9N2 IAIV along with TLR ligands (pam2CSK4, poly (I:C) and imiquimod, alone or combination) in duck MoDCs. Also, the best enhancement effects were showed in combination of pam2CSK4, poly (I:C) and imiquimod group, whereas IFN-α showed no significant enhancement in all experimental groups. In vivo, the results demonstrated that the percentages of CD4+/ CD8+ T lymphocytes, the levels of Th1/Th2 type cytokines and H9N2 HI titers were significant enhanced in combination of pam2CSK4, poly (I:C) and imiquimod group. However, pam2CSK4 alone or combining with imiquimod showed no enhancement or additive effects on Th1 cytokines (IFN-γ and IL-2), Th2 cytokines (IL-6) and HI titers in Muscovy duck, respectively. Taken together, our results concluded that not all TLR ligands showed enhancement of immune responses to H9N2 IAIV in duck. The combination of poly (I:C), imiquimod and pam2CSK4 that can be an effectively adjuvant candidate for H9N2 AIVs inactivated vaccine in duck, which provide novel insights in explore waterfowl vaccine.

摘要

目前的商用 H9 禽流感病毒（AIV）疫苗不能为鸭提供满意的抗体滴度和针对 AIV 的保护免疫力。Toll 样受体（TLR）配体作为 AIV 佐剂可激活树突状细胞，提高多种动物的免疫反应，而在鸭中尚无相关研究。因此，我们研究了 TLR 配体 pam2CSK4、poly（I:C）和/或咪喹莫特是否能增强外周血单核细胞衍生的树突状细胞（MoDCs）和鸭中 H9N2 禽流感灭活抗原（H9N2 IAIV）的免疫反应。体外实验观察到，当 H9N2 IAIV 与 TLR 配体（单独或联合使用 pam2CSK4、poly（I:C）和咪喹莫特）一起作用于鸭 MoDCs 时，转录因子 NF-κB、Th1/Th2 型细胞因子（IFN-γ、IL-2 和 IL-6）和捕捉 H9N2 IAIV 抗原的能力显著上调。同时，在 pam2CSK4、poly（I:C）和咪喹莫特联合组中显示出最佳的增强效果，而 IFN-α 在所有实验组中均无显著增强作用。体内实验结果表明，在 pam2CSK4、poly（I:C）和咪喹莫特联合组中，CD4+/CD8+T 淋巴细胞的百分比、Th1/Th2 型细胞因子的水平和 H9N2 HI 滴度均显著升高。然而，单独使用 pam2CSK4 或与咪喹莫特联合使用在番鸭中对 Th1 细胞因子（IFN-γ 和 IL-2）、Th2 细胞因子（IL-6）和 HI 滴度均无增强或相加作用。总之，我们的研究结果表明，并非所有 TLR 配体对鸭 H9N2 IAIV 的免疫反应均有增强作用。poly（I:C）、咪喹莫特和 pam2CSK4 的联合使用可能是鸭 H9N2 AIV 灭活疫苗的有效佐剂候选物，为水禽疫苗的研究提供了新的思路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e317/9295992/d74961c9fee8/pone.0271746.g006.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e317/9295992/12d42a46d863/pone.0271746.g002.jpg
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