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单磷酰脂质A、寡脱氧核苷酸CpG及联合佐剂对调节流感疫苗接种的天然免疫和适应性免疫反应的不同作用

Distinct Effects of Monophosphoryl Lipid A, Oligodeoxynucleotide CpG, and Combination Adjuvants on Modulating Innate and Adaptive Immune Responses to Influenza Vaccination.

作者信息

Ko Eun-Ju, Lee Young-Tae, Lee Youri, Kim Ki-Hye, Kang Sang-Moo

机构信息

Vaccine Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.

Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303, USA.

出版信息

Immune Netw. 2017 Oct;17(5):326-342. doi: 10.4110/in.2017.17.5.326. Epub 2017 Oct 19.

DOI:10.4110/in.2017.17.5.326
PMID:29093654
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5662782/
Abstract

Monophosphoryl lipid A (MPL) and oligodeoxynucleotide CpG are toll-like receptor (TLR) 4 and 9 agonist, respectively. Here, we investigated the effects of MPL, CpG, and combination adjuvants on stimulating dendritic cells (DCs), innate and adaptive immune responses, and protective efficacy of influenza vaccination. Combination of MPL and CpG was found to exhibit distinct effects on stimulating DCs to secrete IL-12p70 and tumor necrosis factor (TNF)-α and proliferate allogeneic CD8 T cells. Prime immunization of mice with inactivated split influenza vaccine in the presence of low dose MPL+CpG adjuvants increased the induction of virus-specific IgG and IgG2a isotype antibodies. MPL and CpG adjuvants contribute to improving the efficacy of prime influenza vaccination against lethal influenza challenge as determined by body weight monitoring, lung function, viral titers, and histology. A combination of MPL and CpG adjuvants was effective in improving vaccine efficacy as well as in reducing inflammatory immune responses locally and in inducing cellular immune responses upon lethal influenza virus challenge. This study demonstrates unique adjuvant effects of MPL, CpG, and combination adjuvants on modulating innate and adaptive immune responses to influenza prime vaccination.

摘要

单磷酰脂质A（MPL）和寡脱氧核苷酸CpG分别是Toll样受体（TLR）4和9激动剂。在此，我们研究了MPL、CpG及联合佐剂对刺激树突状细胞（DC）、固有免疫和适应性免疫反应以及流感疫苗接种保护效力的影响。结果发现，MPL与CpG联合使用对刺激DC分泌白细胞介素-12p70和肿瘤坏死因子（TNF）-α以及增殖同种异体CD8 T细胞具有显著作用。在低剂量MPL+CpG佐剂存在的情况下，用灭活裂解流感疫苗对小鼠进行初次免疫可增加病毒特异性IgG和IgG2a同种型抗体的诱导。通过体重监测、肺功能、病毒滴度和组织学检查确定，MPL和CpG佐剂有助于提高初次流感疫苗接种对致死性流感攻击的效力。MPL和CpG佐剂联合使用在提高疫苗效力以及减轻局部炎症免疫反应和诱导对致死性流感病毒攻击的细胞免疫反应方面是有效的。本研究证明了MPL、CpG及联合佐剂在调节对流感初次疫苗接种的固有免疫和适应性免疫反应方面具有独特的佐剂作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/30da/5662782/bb6d62da7a01/in-17-326-g008.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/30da/5662782/bb6d62da7a01/in-17-326-g008.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/30da/5662782/8a9a049004e8/in-17-326-g002.jpg
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