Laboratory for Health Protection Research, National Institute for Public Health and the Environment, Bilthoven, The Netherlands.
Hum Vaccin Immunother. 2012 Sep;8(9):1323-5. doi: 10.4161/hv.21350. Epub 2012 Sep 1.
Dendritic cells (DC) are pivotal in the induction of adaptive immune responses because they can activate naive T-cells. Moreover, they steer these adaptive immune responses by integrating various stimuli, such as from different pathogen associated molecular patterns and the cytokine milieu. Immature DC are very well capable of ingesting protein antigens, whereas mature DC are efficient presenters of peptides to naive T cells. Human DC can be readily cultured from peripheral blood mononuclear cells, which are isolated from human blood. There is a strong need to monitor in a high-throughput fashion the immunogenicity of candidate vaccines during the process of vaccine development. Furthermore, regulators require efficacy and safety testing for batch release. For some vaccines, these tests require animal testing, causing pain and discomfort, which cannot be contested because it would interfere with the test results. With the aims of promoting vaccine development and reducing the number of animals for batch release testing, we propose to use more broadly human DC for vaccine immunogenicity testing. In this commentary, this proposition is illustrated by several examples in which the maturation of human DC was successfully used to test for vaccine and adjuvant immunogenicity.
树突状细胞 (DC) 在诱导适应性免疫反应中起着关键作用,因为它们能够激活初始 T 细胞。此外,它们通过整合来自不同病原体相关分子模式和细胞因子环境的各种刺激来引导这些适应性免疫反应。未成熟的 DC 非常擅长摄取蛋白质抗原,而成熟的 DC 则能够有效地将肽呈递给初始 T 细胞。人 DC 可以从外周血单核细胞中轻易培养出来,外周血单核细胞是从人血液中分离出来的。在疫苗开发过程中,人们强烈需要以高通量的方式监测候选疫苗的免疫原性。此外,监管机构需要对批次放行进行疗效和安全性测试。对于一些疫苗,这些测试需要进行动物测试,这会导致疼痛和不适,因为这会干扰测试结果,所以无法反对。为了促进疫苗开发和减少用于批次放行测试的动物数量,我们建议更广泛地使用人 DC 进行疫苗免疫原性测试。在这篇评论中,通过几个例子说明了这一建议,其中成功地使用人 DC 的成熟来测试疫苗和佐剂的免疫原性。