Hasegawa Hideki, Ichinohe Takeshi, Strong Peter, Watanabe Izumi, Ito Satoshi, Tamura Shin-Ichi, Takahashi Hidehiro, Sawa Hirofumi, Chiba Joe, Kurata Takeshi, Sata Tetsutaro
Department of Pathology, National Institute of Infectious Diseases, 4-7-1 Gakuen, Musashimurayama-shi, Tokyo 208-0011, Japan.
J Med Virol. 2005 Jan;75(1):130-6. doi: 10.1002/jmv.20247.
Chitin in the form of microparticles (chitin microparticles, CMP) has been demonstrated to be a potent stimulator of macrophages, promoting T-helper-1 (Th1) activation and cytokine response. In order to examine the mucosal adjuvant effect of CMP co-administered with influenza hemagglutinin (HA) vaccine against influenza infection, CMP were intranasally co-administered with influenza HA vaccine prepared from PR8 (H1N1) virus. Inoculation of the vaccine with CMP induced primary and secondary anti-HA IgA responses in the nasal wash and anti-HA IgG responses in the serum, which were significantly higher than those of nasal vaccination without CMP, and provided a complete protection against a homologous influenza virus challenge in the nasal infection influenza model. In addition, CMP-based immunization using A/Yamagata (H1N1) and A/Guizhou (H3N2) induced PR8 HA-reactive IgA in the nasal washes and specific-IgG in the serum. The immunization with A/Yamagata and CMP resulted in complete protection against a PR8 (H1N1) challenge in A/Yamagata (H1N1)-vaccinated mice, while that with A/Guizhou (H3N2) and CMP exhibited a 100-fold reduction of nasal virus titer, demonstrating the cross-protective effect of CMP and influenza vaccine. It is suggested that CMP provide a safe and effective adjuvant for nasal vaccination with inactivated influenza vaccine.
微粒形式的几丁质(几丁质微粒,CMP)已被证明是巨噬细胞的有效刺激剂,可促进辅助性T细胞1(Th1)激活和细胞因子反应。为了研究CMP与流感血凝素(HA)疫苗联合使用对流感感染的黏膜佐剂作用,将CMP与由PR8(H1N1)病毒制备的流感HA疫苗经鼻联合给药。用CMP接种疫苗可诱导鼻腔灌洗液中的初次和二次抗HA IgA反应以及血清中的抗HA IgG反应,这些反应显著高于未使用CMP的鼻腔接种,并在鼻腔感染流感模型中提供了针对同源流感病毒攻击的完全保护。此外,使用A/山形(H1N1)和A/贵州(H3N2)进行基于CMP的免疫接种可诱导鼻腔灌洗液中产生PR8 HA反应性IgA和血清中的特异性IgG。用A/山形和CMP进行免疫接种可使接种A/山形(H1N1)的小鼠对PR8(H1N1)攻击产生完全保护,而用A/贵州(H3N2)和CMP进行免疫接种可使鼻腔病毒滴度降低100倍,证明了CMP和流感疫苗的交叉保护作用。提示CMP为灭活流感疫苗的鼻腔接种提供了一种安全有效的佐剂。