Distinct Effects of Monophosphoryl Lipid A, Oligodeoxynucleotide CpG, and Combination Adjuvants on Modulating Innate and Adaptive Immune Responses to Influenza Vaccination.
Distinct Effects of Monophosphoryl Lipid A, Oligodeoxynucleotide CpG, and Combination Adjuvants on Modulating Innate and Adaptive Immune Responses to Influenza Vaccination.
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DOI：
10.4110/in.2017.17.5.326
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发表时间：
2017-10
期刊：
影响因子：
6
通讯作者：
Kang SM
中科院分区：
文献类型：
--
作者：
Ko EJ;Lee YT;Lee Y;Kim KH;Kang SM
单磷脂A(MPL)和寡核苷酸CpG分别为Toll样受体(TLR)4和9激动剂。在这里，我们研究了MPL、CpG和联合佐剂对体外刺激树突状细胞(DC)、体内天然和获得性免疫反应的影响，以及流感疫苗的保护效果。MPL和CpG联合应用对体外培养的DC分泌IL-12p70和肿瘤坏死因子-α及增殖同种异体CD8T细胞有明显的刺激作用。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始免疫，可增加病毒特异性IgG和IgG2a亚型抗体的诱导。根据体重监测、肺功能、病毒滴度和组织学的测定，MPL和CpG佐剂有助于提高初级流感疫苗接种对抗致命流感挑战的有效性。联合使用MPL和CpG佐剂可有效提高疫苗效力，减少局部炎性免疫反应，并诱导对致死性流感病毒攻击的细胞免疫反应。这项研究展示了MPL、CpG和联合佐剂在调节流感初级疫苗的先天和获得性免疫反应方面的独特佐剂作用。
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 in vitro dendritic cells (DCs), in vivo 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 in vitro 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.
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DOI：
10.1084/jem.20101850
发表时间：
2011-01-17
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Hufford MM;Kim TS;Sun J;Braciale TJ
通讯作者：
Braciale TJ
影响因子：
56.9
作者：
Mata-Haro, Veronica;Cekic, Caglar;Mitchell, Thomas C.
通讯作者：
Mitchell, Thomas C.
影响因子：
5.5
作者：
Heikkinen, Terho;Heinonen, Santtu
通讯作者：
Heinonen, Santtu
影响因子：
4.4
作者：
Heer, Alex K.;Shamshiev, Abdijapar;Marsland, Benjamin J.
通讯作者：
Marsland, Benjamin J.
影响因子：
5.4
作者：
Hua, Laiqing;Yao, Shuyu;Sun, Jie
通讯作者：
Sun, Jie