Department of Comparative Pathobiology, College of Veterinary Medicine, Purdue University, West Lafayette, IN 47907, USA.
Vaccine. 2013 Aug 20;31(37):3979-86. doi: 10.1016/j.vaccine.2013.05.107. Epub 2013 Jun 14.
Aluminum-containing adjuvants are widely used in human and veterinary vaccines, but their mechanism of action is not well understood. Recent evidence suggests an important role for inflammation in the immune response to aluminum-adjuvanted vaccines. To better understand this process, vaccines with aluminum adjuvant were injected into naïve or previously immunized mice and the injection sites were characterized for the corresponding primary and secondary inflammatory response at different time points after immunization. Inflammatory cells appeared at the injection site between 2h and 6h after vaccination, dominated by neutrophils at first, followed by macrophages, and later eosinophils and MHCII(+) cells. The number of cells at the injection site increased over time, except neutrophils, which decreased in number after day 2. There was extensive phagocytosis of aluminum adjuvant particles by macrophages. In secondary immunized mice, a faster and more robust recruitment of eosinophils, macrophages, and antigen presenting cells was observed at the injection site. The enhanced recruitment of inflammatory cells in previously immunized mice coincided with increased expression of relevant chemokines at the injection site. Since neutrophils accumulated first in response to aluminum-adjuvanted vaccines, their role was evaluated by depleting them prior to vaccination. Neutrophil depletion transiently reduced the recruitment of macrophages but it did not change the recruitment of eosinophils and MHCII(+) cells or the quality and magnitude of the antibody response.
含铝佐剂广泛应用于人类和兽医疫苗中，但它们的作用机制尚不清楚。最近的证据表明，炎症在对铝佐剂疫苗的免疫反应中起着重要作用。为了更好地理解这一过程，将含铝佐剂的疫苗注射到未免疫或先前免疫的小鼠体内，并在免疫后不同时间点对注射部位的相应原发性和继发性炎症反应进行特征分析。炎症细胞在接种后 2 至 6 小时出现在注射部位，最初以中性粒细胞为主，随后是巨噬细胞，然后是嗜酸性粒细胞和 MHCII(+)细胞。注射部位的细胞数量随时间增加，但中性粒细胞除外，其数量在第 2 天后减少。巨噬细胞对铝佐剂颗粒有广泛的吞噬作用。在二次免疫的小鼠中，在注射部位观察到嗜酸性粒细胞、巨噬细胞和抗原呈递细胞更快、更强的募集。先前免疫的小鼠中炎症细胞的募集增加与注射部位相关趋化因子的表达增加相一致。由于中性粒细胞对铝佐剂疫苗的反应首先积累，因此在接种疫苗前对其进行耗竭以评估其作用。中性粒细胞耗竭会短暂减少巨噬细胞的募集，但不会改变嗜酸性粒细胞和 MHCII(+)细胞的募集，也不会改变抗体反应的质量和数量。
