免疫应答对吸附于氢氧化铝颗粒上的抗原:佐剂 ALF 或 ALFQ 与铝-抗原复合物共吸附的影响。
Immune response to antigen adsorbed to aluminum hydroxide particles: Effects of co-adsorption of ALF or ALFQ adjuvant to the aluminum-antigen complex.
机构信息
U.S. Military HIV Research Program, Henry M. Jackson Foundation for the Advancement of Military Medicine, 6720A Rockledge Drive, Bethesda, MD 20817, USA; Laboratory of Adjuvant and Antigen Research, US Military HIV Research Program, Walter Reed Army Institute of Research, 503 Robert Grant Avenue, Silver Spring, MD 20910, USA.
Laboratory of Adjuvant and Antigen Research, US Military HIV Research Program, Walter Reed Army Institute of Research, 503 Robert Grant Avenue, Silver Spring, MD 20910, USA.
出版信息
J Control Release. 2018 Apr 10;275:12-19. doi: 10.1016/j.jconrel.2018.02.006. Epub 2018 Feb 9.
Aluminum salts have been used as vaccine adjuvants for >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.
铝盐已被用作疫苗佐剂超过 50 年,目前全球至少有 146 种已许可的疫苗中含有铝盐。在这项研究中,我们研究了吸附到已吸附抗原的铝盐上的 Army Liposome Formulation(ALF)是否会提高吸附抗原的铝佐剂的免疫原性。ALF 由一系列阴离子脂质体佐剂组成,其中脂质体含有具有二肉豆蔻酰基脂肪酸酰基的合成磷脂、胆固醇和单磷酰脂质 A(MPLA)。对于某些候选疫苗,ALF 已添加到氢氧化铝(AH)凝胶中作为第二种佐剂以形成 ALFA。在这里,我们表明 ALF 的不同制备方法改变了 ALF 和 ALFA 的物理结构。含有皂苷 QS21 的脂质体(ALFQ)也已与 AH 混合形成 ALFQA,作为一种有效的组合。在这项研究中,我们首先将两种不同抗原中的一种吸附到 AH 上,一种是与 34 个半抗原(MorHap)缀合的破伤风类毒素,已用于候选海洛因疫苗,另一种是源自 HIV-1 包膜蛋白的 gp140 蛋白。然后我们将 ALF 或 ALFQ 共同吸附到 AH 上形成 ALFA 或 ALFQA。在每种情况下,将 ALF 或 ALFQ 共同吸附到 AH 上都大大提高了吸附到 AH 上的抗原的免疫原性。通过 ELISPOT 进行 IgG 亚型和细胞因子分析,ALFA 诱导主要是 Th2 型反应,而 ALFQ 和 ALFQA 各自诱导更平衡的 Th1/Th2 反应。