Youn Hyun-Jun, Ko Sung-Youl, Lee Kyoo-A, Ko Hyun-Jeong, Lee Yoon-Sook, Fujihashi Kohtaro, Boyaka Prosper N, Kim Sang-Hee, Horimoto Taisuke, Kweon Mi-Na, Kang Chang-Yuil
Laboratory of Immunology, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Korea.
Vaccine. 2007 Jul 9;25(28):5189-98. doi: 10.1016/j.vaccine.2007.04.081. Epub 2007 May 21.
alpha-Galactosylceramide (alpha-GalCer), originally isolated from a marine sponge, was known to activate natural killer T (NKT) cells through CD1d-mediated Ag presentation and induce Th1 and/or Th2 immunity. In this study, we evaluated the nasal adjuvanticity of alpha-GalCer when co-administered with formalin-inactivated influenza virus A/PR/8/34 (PR8) in BALB/c mice. A single nasal immunization of inactivated PR8 and alpha-GalCer induced brisk levels of PR8-specific IgG and IgA Abs in serum and lung washes. Antigen-specific Ab responses lasted for 3 months, providing protective immunity against challenge with live PR8. In addition, mice given alpha-GalCer also exhibited cellular immune responses including cytotoxic T lymphocyte (CTL) generation. Because it did not redirect Ags into brain, alpha-GalCer would likely pose no risk if administered as a nasal adjuvant. These results suggest for the first time that a single nasal immunization of inactivated virus and alpha-GalCer is a safe and effective means of preventing influenza infection.
α-半乳糖神经酰胺（α-GalCer）最初是从一种海洋海绵中分离出来的，已知它可通过CD1d介导的抗原呈递激活自然杀伤T（NKT）细胞，并诱导Th1和/或Th2免疫。在本研究中，我们评估了α-GalCer与福尔马林灭活的甲型流感病毒A/PR/8/34（PR8）共同给药时在BALB/c小鼠中的鼻腔佐剂活性。对灭活的PR8和α-GalCer进行单次鼻腔免疫可诱导血清和肺灌洗液中PR8特异性IgG和IgA抗体的活跃水平。抗原特异性抗体反应持续3个月，提供针对活PR8攻击的保护性免疫。此外，给予α-GalCer的小鼠还表现出细胞免疫反应，包括细胞毒性T淋巴细胞（CTL）的产生。由于α-GalCer不会将抗原重定向到大脑，如果作为鼻腔佐剂给药，它可能不会有风险。这些结果首次表明，对灭活病毒和α-GalCer进行单次鼻腔免疫是预防流感感染的一种安全有效的方法。
