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单一溶血磷脂酰胆碱成分在体外和体内均表现出佐剂活性。

Single lysophosphatidylcholine components exhibit adjuvant activities in vitro and in vivo.

作者信息

Bach Guillaume, Perrin-Cocon Laure, Gerossier Estelle, Guironnet-Paquet Aurélie, Lotteau Vincent, Inchauspé Geneviève, Fournillier Anne

机构信息

TRANSGENE S.A., Centre d'Infectiologie, Domilyon Building, Lyon 69007, France.

出版信息

Clin Vaccine Immunol. 2010 Mar;17(3):429-38. doi: 10.1128/CVI.00420-09. Epub 2010 Jan 13.

Abstract

Improving vaccine immunogenicity by developing new adjuvant formulations has long been a goal of vaccinologists. It has previously been shown that a natural mix of lysophosphatidylcholine (LPC) from chicken eggs promotes mature dendritic cell (DC) generation in vitro and primes antigen-specific immune responses in mice. In the present study, we dissected the adjuvant potentials of five individual LPC components found in the chicken egg mixture. In vitro analyses of the impact of the individual components on the maturation of human DCs were performed by means of phenotypic analysis, chemokine secretion analysis, and analysis of the ability of mature DC to stimulate T lymphocytes. Two components, C16:0-LPC and C18:0-LPC, were identified to be capable of the upregulation of expression of CD86, HLA-DR, and CD40 on in vitro-cultured monocyte-derived DCs from healthy donors. Both induced the release of chemokines to high concentrations (macrophage inflammatory protein 1, monocyte chemoattractant protein 1) or moderate concentrations (interleukin-8 [IL-8], gamma interferon-inducible protein 10). In addition, C16:0-LPC engaged naïve T cells to produce gamma interferon. This suggests that C16:0-LPC and C18:0-LPC have the capacity to promote, at least in vitro, a Th1-oriented response. The intravenous injection of C16:0-LPC or C18:0-LPC into mice resulted in the detectable secretion of IL-6 and IL-5 in sera. Both LPC components were tested for their capacities to act as adjuvants for two selected immunogens: the hepatitis B virus surface antigen and the hepatitis C virus NS3 helicase. The secretion of specific IgG1 was observed with either or both C16:0-LPC and C18:0-LPC, depending on the immunogen tested, and was observed at an efficiency comparable to that of alum. These data identify C16:0-LPC and C18:0-LPC as the active components of the LPC natural mixture. Although discrepancies between the results of the in vitro and in vivo analyses existed, studies with animals suggest that these components can trigger significant and specific humoral-mediated immunity.

摘要

通过开发新的佐剂配方来提高疫苗免疫原性一直是疫苗学家的目标。此前已有研究表明,来自鸡蛋的溶血磷脂酰胆碱(LPC)天然混合物可在体外促进成熟树突状细胞(DC)的生成,并在小鼠中引发抗原特异性免疫反应。在本研究中,我们剖析了鸡蛋混合物中发现的五种单个LPC成分的佐剂潜力。通过表型分析、趋化因子分泌分析以及成熟DC刺激T淋巴细胞能力的分析,对单个成分对人DC成熟的影响进行了体外分析。鉴定出两种成分,C16:0-LPC和C18:0-LPC,能够上调健康供体体外培养的单核细胞来源DC上CD86、HLA-DR和CD40的表达。两者均诱导趋化因子释放至高浓度(巨噬细胞炎性蛋白1、单核细胞趋化蛋白1)或中等浓度(白细胞介素-8 [IL-8]、γ干扰素诱导蛋白10)。此外,C16:0-LPC促使未活化的T细胞产生γ干扰素。这表明C16:0-LPC和C18:0-LPC至少在体外有促进Th1型反应的能力。将C16:0-LPC或C18:0-LPC静脉注射到小鼠体内会导致血清中可检测到IL-6和IL-5的分泌。测试了这两种LPC成分作为两种选定免疫原(乙型肝炎病毒表面抗原和丙型肝炎病毒NS3解旋酶)佐剂的能力。根据所测试的免疫原,使用C16:0-LPC和C18:0-LPC中的一种或两种均观察到特异性IgG1的分泌,并且观察到的效率与明矾相当。这些数据确定C16:0-LPC和C18:0-LPC为LPC天然混合物的活性成分。尽管体外和体内分析结果存在差异,但动物研究表明这些成分可引发显著的特异性体液介导免疫。

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