Perrin-Cocon Laure, Agaugué Sophie, Coutant Frédéric, Saint-Mézard Pierre, Guironnet-Paquet Aurélie, Nicolas Jean-François, André Patrice, Lotteau Vincent
Institut Fédératif de Recherche 128, Institut National de la Santé et de la Recherche Médicale U503, 21 Avenue Tony Garnier, 69007 Lyon, France.
Vaccine. 2006 Feb 27;24(9):1254-63. doi: 10.1016/j.vaccine.2005.09.036. Epub 2005 Sep 30.
The discovery of new adjuvants that can stimulate the immune response to protein antigens is a major issue for the development of subunit vaccines. Lipoprotein oxidation occurring during the acute phase response (APR) to aggression of the organism, provides signals of danger that are detected by dendritic cells (DC). Among other instructive molecules generated during the APR, lysophosphatidylcholine (LPC) promotes mature DC generation from differentiating human monocytes in vitro. It is shown here that LPC also controls the initiation of an adaptive immune response in vivo. LPC displays adjuvant properties when injected to mice in mixture with various antigens. Immunizations with LPC induced the production of antigen-specific antibodies with an efficiency similar to Alum, the reference adjuvant for human vaccination. Importantly, LPC also induced cytotoxic T cell responses, opening perspectives for vaccine development. Therefore, LPC is a natural adjuvant for the immune system, inducing humoral and cellular immune responses.
发现能够刺激对蛋白质抗原免疫反应的新型佐剂是亚单位疫苗研发的一个主要问题。机体受到侵袭时,急性期反应(APR)过程中发生的脂蛋白氧化会产生危险信号,这些信号由树突状细胞(DC)检测到。在APR过程中产生的其他具有指导作用的分子中,溶血磷脂酰胆碱(LPC)能在体外促进分化中的人单核细胞生成成熟的DC。本文表明,LPC在体内也能控制适应性免疫反应的启动。当与各种抗原混合注射给小鼠时,LPC表现出佐剂特性。用LPC免疫可诱导产生抗原特异性抗体,其效率与人类疫苗接种的参考佐剂明矾相似。重要的是,LPC还能诱导细胞毒性T细胞反应,为疫苗研发开辟了前景。因此,LPC是免疫系统的天然佐剂,可诱导体液免疫和细胞免疫反应。