Development and characterization of synthetic glucopyranosyl lipid adjuvant system as a vaccine adjuvant.
Development and characterization of synthetic glucopyranosyl lipid adjuvant system as a vaccine adjuvant.
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DOI：
10.1371/journal.pone.0016333
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发表时间：
2011-01-26
期刊：
影响因子：
3.7
通讯作者：
Reed SG
中科院分区：
文献类型：
--
作者：
Coler RN;Bertholet S;Moutaftsi M;Guderian JA;Windish HP;Baldwin SL;Laughlin EM;Duthie MS;Fox CB;Carter D;Friede M;Vedvick TS;Reed SG
对基于脂多糖（LPS）（革兰氏阴性细菌细胞壁的组分）的疫苗佐剂的先天免疫应答由Toll样受体（TLR）4和衔接蛋白（包括MyD88和TRIF）驱动，导致产生炎性细胞因子、I型干扰素和趋化因子。我们在这里报告的表征合成的六酰化脂质A衍生物，表示为吡喃葡萄糖基脂质佐剂（GLA）。我们评估了GLA对小鼠和人树突状细胞（DC）的影响相结合的芯片，mRNA和蛋白质的多重分析和流式细胞仪分析。我们证明，GLA具有多功能的免疫调节活性类似于天然来源的单磷脂质A（MPL）对小鼠DC，包括生产炎症细胞因子，趋化因子，DC成熟和抗原呈递功能。相比之下，当在人DC和外周血单核细胞（PBMC）上测试时，六酰化GLA在摩尔基础上总体上比异质MPL更有效。当在体内给药时，GLA增强了共同给药的重组抗原的免疫原性，产生强的细胞介导的免疫和定性的TH1应答。我们的结论是，GLA佐剂刺激和指导先天性和适应性免疫反应，诱导DC成熟和伴随释放的促炎细胞因子和趋化因子与免疫细胞的贩运，活动具有重要意义的发展，未来的疫苗佐剂。
Innate immune responses to vaccine adjuvants based on lipopolysaccharide (LPS), a component of Gram-negative bacterial cell walls, are driven by Toll-like receptor (TLR) 4 and adaptor proteins including MyD88 and TRIF, leading to the production of inflammatory cytokines, type I interferons, and chemokines. We report here on the characterization of a synthetic hexaacylated lipid A derivative, denoted as glucopyranosyl lipid adjuvant (GLA). We assessed the effects of GLA on murine and human dendritic cells (DC) by combining microarray, mRNA and protein multiplex assays and flow cytometry analyses. We demonstrate that GLA has multifunctional immunomodulatory activity similar to naturally-derived monophosphory lipid A (MPL) on murine DC, including the production of inflammatory cytokines, chemokines, DC maturation and antigen-presenting functions. In contrast, hexaacylated GLA was overall more potent on a molar basis than heterogeneous MPL when tested on human DC and peripheral blood mononuclear cells (PBMC). When administered in vivo, GLA enhanced the immunogenicity of co-administered recombinant antigens, producing strong cell-mediated immunity and a qualitative TH1 response. We conclude that the GLA adjuvant stimulates and directs innate and adaptive immune responses by inducing DC maturation and the concomitant release of pro-inflammatory cytokines and chemokines associated with immune cell trafficking, activities which have important implications for the development of future vaccine adjuvants.
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影响因子：
5.5
作者：
Nascimento, Evaldo;Fernandes, Demetrios F.;Piazza, Franco M.
通讯作者：
Piazza, Franco M.
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：
5.8
作者：
Anderson, Ryan C.;Fox, Christopher B.;Vedvick, Thomas S.
通讯作者：
Vedvick, Thomas S.
DOI：
10.1084/jem.20052545
发表时间：
2006-07-10
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Khader SA;Partida-Sanchez S;Bell G;Jelley-Gibbs DM;Swain S;Pearl JE;Ghilardi N;Desauvage FJ;Lund FE;Cooper AM
通讯作者：
Cooper AM
影响因子：
5.5
作者：
Baldwin, Susan L.;Shaverdian, Narek;Reed, Steven G.
通讯作者：
Reed, Steven G.