Weinberger Birgit, Joos Clemens, Reed Steven G, Coler Rhea, Grubeck-Loebenstein Beatrix
Institute for Biomedical Aging Research, University of Innsbruck, Rennweg 10, 6020, Innsbruck, Austria.
Infectious Disease Research Institute, 1616 Eastlake Ave E #400, Seattle, WA, 98102, USA.
Biogerontology. 2016 Feb;17(1):177-87. doi: 10.1007/s10522-015-9576-x. Epub 2015 May 9.
Many subunit vaccines require adjuvants to improve their limited immunogenicity. Various adjuvant candidates targeting toll-like receptors (TLRs) are currently under development including the synthetic TLR4 agonist glucopyranosyl lipid A (GLA). GLA has been investigated in the context of influenza vaccine, which is of particular importance for the elderly population. This study investigates the effect of GLA on antigen-presenting cells from young (median age 29 years, range 26-33 years) and older (median age 72 years, range 61-78 years) adults. Treatment with GLA efficiently increases the expression of co-stimulatory molecules on human monocyte-derived dendritic cells (DC) as well as on ex vivo myeloid DC. Expression of co-stimulatory molecules is less pronounced on ex vivo monocytes. Production of pro-inflammatory cytokines (IL-6, TNF-α, IL-12) as well as of the anti-inflammatory cytokine IL-10 is induced in monocyte-derived DC. In PBMC cultures myeloid DC and to an even greater extent monocytes produce TNF-α and IL-6 after stimulation with GLA. Production of IL-12 can also be observed in these cultures. There are no age-related differences in the capacity of GLA to induce expression of co-stimulatory molecules or production of cytokines by human antigen-presenting cells. Therefore, TLR4 agonists like GLA are particularly promising candidates as adjuvants of vaccines designed for elderly individuals.
许多亚单位疫苗需要佐剂来改善其有限的免疫原性。目前正在研发多种靶向 Toll 样受体（TLR）的佐剂候选物，包括合成的 TLR4 激动剂吡喃葡萄糖基脂质 A（GLA）。GLA 已在流感疫苗的背景下进行了研究，这对老年人群尤为重要。本研究调查了 GLA 对年轻成年人（中位年龄 29 岁，范围 26 - 33 岁）和年长成年人（中位年龄 72 岁，范围 61 - 78 岁）抗原呈递细胞的影响。用 GLA 处理可有效增加人单核细胞衍生树突状细胞（DC）以及体外髓样 DC 上共刺激分子的表达。共刺激分子在体外单核细胞上的表达不太明显。单核细胞衍生 DC 中诱导产生促炎细胞因子（IL - 6、TNF - α、IL - 12）以及抗炎细胞因子 IL - 10。在 PBMC 培养物中，髓样 DC 以及在更大程度上单核细胞在 GLA 刺激后产生 TNF - α 和 IL - 6。在这些培养物中也可观察到 IL - 12 的产生。GLA 诱导人抗原呈递细胞共刺激分子表达或细胞因子产生的能力不存在年龄相关差异。因此，像 GLA 这样的 TLR4 激动剂作为针对老年人设计的疫苗佐剂是特别有前景的候选物。
