Immune response to antigen adsorbed to aluminum hydroxide particles: Effects of co-adsorption of ALF or ALFQ adjuvant to the aluminum-antigen complex.
Immune response to antigen adsorbed to aluminum hydroxide particles: Effects of co-adsorption of ALF or ALFQ adjuvant to the aluminum-antigen complex.
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DOI：
10.1016/j.jconrel.2018.02.006
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发表时间：
2018-04-10
期刊：
影响因子：
--
通讯作者：
Alving CR
中科院分区：
文献类型：
--
作者：
Beck Z;Torres OB;Matyas GR;Lanar DE;Alving CR
铝盐已被用作疫苗佐剂超过50年，目前在全球至少有146种已获许可的疫苗中使用。在这项研究中，我们检查了Army脂质体制剂（ALF）吸附到已经吸附了抗原的铝盐上是否会导致铝吸附抗原的免疫效力提高。ALF由一系列基于阴离子脂质体的佐剂组成，其中脂质体含有具有二肉豆蔻酰脂肪酰基的合成磷脂、胆固醇和单磷酰脂质A（MPLA）。对于某些候选疫苗，ALF已被添加到氢氧化铝（AH）凝胶中作为第二佐剂以形成ALFA。在这里，我们表明，不同的方法制备ALF改变了ALF和ALFA的物理结构。含有皂苷QS 21（ALFQ）的脂质体也与AH混合以形成ALFQA作为有效组合。在这项研究中，我们首先将两种不同抗原之一吸附到AH上，要么是与34个半抗原（MorHap）拷贝缀合的破伤风类毒素（已用于候选海洛因疫苗），要么是来自HIV-1包膜蛋白的gp 140蛋白。然后我们将ALF或ALFQ共吸附到AH上以形成ALFA或ALFQA。在每种情况下，通过将ALF或ALFQ共吸附到AH上，吸附到AH上的抗原的免疫效力大大增加。基于ELISPOT的IgG亚型和细胞因子分析，ALFA主要诱导Th 2型应答，ALFQ和ALFQA各自诱导更平衡的Th 1/Th 2应答。
Aluminum salts have been used as vaccine adjuvants for more than 50 years, and they are currently present in at least 146 licensed vaccines worldwide. In this study we examined whether adsorption of Army Liposome Formulation (ALF) to an aluminum salt that already has an antigen adsorbed to it might result in improved immune potency of the aluminum-adsorbed antigen. ALF is composed of a family of anionic liposome-based adjuvants, in which the liposomes contain synthetic phospholipids having dimyristoyl fatty acyl groups, cholesterol and monophosphoryl lipid A (MPLA). For certain candidate vaccines, ALF has been added to aluminum hydroxide (AH) gel as a second adjuvant to form ALFA. Here we show that different methods of preparation of ALF changed the physical structures of both ALF and ALFA. Liposomes containing the saponin QS21 (ALFQ) have also been mixed with AH to form ALFQA as an effective combination. In this study, we first adsorbed one of two different antigens to AH, either tetanus toxoid conjugated to 34 copies of a hapten (MorHap), which has been used in a candidate heroin vaccine, or gp140 protein derived from the envelope protein of HIV-1. We then co-adsorbed ALF or ALFQ to the AH to form ALFA or ALFQA. In each case, the immune potency of the antigen adsorbed to AH was greatly increased by co-adsorbing either ALF or ALFQ to the AH. Based on IgG subtype and cytokine analysis by ELISPOT, ALFA induced predominately a Th2-type response and ALFQ and ALFQA each induced more balanced Th1/Th2 responses.
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影响因子：
5.5
作者：
Ambrosch, F;Wiedermann, G;Thoelen, S
通讯作者：
Thoelen, S
DOI：
10.1073/pnas.89.1.358
发表时间：
1992-01-01
影响因子：
11.1
作者：
FRIES, LF;GORDON, DM;ALVING, CR
通讯作者：
ALVING, CR
影响因子：
7.3
作者：
Hogenesch H
通讯作者：
Hogenesch H
影响因子：
4.8
作者：
Hickman, David T.;Lopez-Deber, Maria Pilar;Muhs, Andreas
通讯作者：
Muhs, Andreas
影响因子：
4.7
作者：
Jalah, Rashmi;Torres, Oscar B.;Mayorov, Alexander V.;Li, Fuying;Antoline, Joshua F. G.;Jacobson, Arthur E.;Rice, Kenner C.;Deschamps, Jeffrey R.;Beck, Zoltan;Alving, Carl R.;Matyas, Gary R.
通讯作者：
Matyas, Gary R.