Department of Medicine Solna, Division of Immunology and Allergy, Karolinska Institutet and University Hospital, 171 64 Stockholm, Sweden; Center for Molecular Medicine, Karolinska Institutet, 171 77 Stockholm, Sweden.
IAVI Neutralizing Antibody Center, Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Cell Rep. 2020 Mar 24;30(12):3964-3971.e7. doi: 10.1016/j.celrep.2020.02.111.
Although intramuscular (i.m.) administration is the most commonly used route for licensed vaccines, subcutaneous (s.c.) delivery is being explored for several new vaccines under development. Here, we use rhesus macaques, physiologically relevant to humans, to identify the anatomical compartments and early immune processes engaged in the response to immunization via the two routes. Administration of fluorescently labeled HIV-1 envelope glycoprotein trimers displayed on liposomes enables visualization of targeted cells and tissues. Both s.c. and i.m. routes induce efficient immune cell infiltration, activation, and antigen uptake, functions that are tightly restricted to the skin and muscle, respectively. Antigen is also transported to different lymph nodes depending on route. However, these early differences do not translate into significant differences in the magnitude or quality of antigen-specific cellular and humoral responses over time. Thus, although some distinct immunological differences are noted, the choice of route may instead be motivated by clinical practicality.
虽然肌肉内（i.m.）给药是已获许可疫苗最常使用的途径，但皮下（s.c.）给药正在被探索用于几种新开发的疫苗。在这里，我们使用与人类生理相关的恒河猴来确定用于免疫接种的两种途径所涉及的解剖隔室和早期免疫过程。通过荧光标记的脂质体展示 HIV-1 包膜糖蛋白三聚体的给药使靶向细胞和组织的可视化成为可能。皮下和肌肉内途径均可诱导有效的免疫细胞浸润、激活和抗原摄取，这些功能分别受到皮肤和肌肉的严格限制。根据途径的不同，抗原也会被运送到不同的淋巴结。然而，这些早期差异并没有转化为随着时间的推移，抗原特异性细胞和体液反应的数量或质量的显著差异。因此，尽管观察到了一些明显的免疫学差异，但选择途径的依据可能更多的是临床实用性。
