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以几丁质微粒作为佐剂经鼻内给予血凝素疫苗预防流感病毒感染

Protection against influenza virus infection by intranasal administration of hemagglutinin vaccine with chitin microparticles as an adjuvant.

作者信息

Hasegawa Hideki, Ichinohe Takeshi, Strong Peter, Watanabe Izumi, Ito Satoshi, Tamura Shin-Ichi, Takahashi Hidehiro, Sawa Hirofumi, Chiba Joe, Kurata Takeshi, Sata Tetsutaro

机构信息

Department of Pathology, National Institute of Infectious Diseases, 4-7-1 Gakuen, Musashimurayama-shi, Tokyo 208-0011, Japan.

出版信息

J Med Virol. 2005 Jan;75(1):130-6. doi: 10.1002/jmv.20247.

Abstract

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.

摘要

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。

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