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鼻内疫苗用蘑菇菌丝体提取物诱导针对甲型流感病毒 H5N1 的交叉保护免疫。

Induction of cross-protective immunity against influenza A virus H5N1 by an intranasal vaccine with extracts of mushroom mycelia.

机构信息

Department of Pathology, National Institute of Infectious Diseases, Musashimurayama-shi, Tokyo, Japan.

出版信息

J Med Virol. 2010 Jan;82(1):128-37. doi: 10.1002/jmv.21670.

DOI:10.1002/jmv.21670
PMID:19950232
Abstract

The identification of a safe and effective adjuvant that is able to enhance mucosal immune responses is necessary for the development of an efficient inactivated intranasal influenza vaccine. The present study demonstrated the effectiveness of extracts of mycelia derived from edible mushrooms as adjuvants for intranasal influenza vaccine. The adjuvant effect of extracts of mycelia was examined by intranasal co-administration of the extracts and inactivated A/PR8 (H1N1) influenza virus hemagglutinin (HA) vaccine in BALB/c mice. The inactivated vaccine in combination with mycelial extracts induced a high anti-A/PR8 HA-specific IgA and IgG response in nasal washings and serum, respectively. Virus-specific cytotoxic T-lymphocyte responses were also induced by administration of the vaccine with extract of mycelia, resulting in protection against lethal lung infection with influenza virus A/PR8. In addition, intranasal administration of NIBRG14 vaccine derived from the influenza A/Vietnam/1194/2004 (H5N1) virus strain administered in conjunction with mycelial extracts from Phellinus linteus conferred cross-protection against heterologous influenza A/Indonesia/6/2005 virus challenge in the nasal infection model. In addition, mycelial extracts induced proinflammatory cytokines and CD40 expression in bone marrow-derived dendritic cells. These results suggest that mycelial extract-adjuvanted vaccines can confer cross-protection against variant H5N1 influenza viruses. The use of extracts of mycelia derived from edible mushrooms is proposed as a new safe and effective mucosal adjuvant for use for nasal vaccination against influenza virus infection.

摘要

为了开发高效的鼻内流感灭活疫苗,有必要鉴定一种安全有效的佐剂,以增强黏膜免疫反应。本研究证实了从食用蘑菇中提取的菌丝体提取物作为鼻内流感疫苗佐剂的有效性。通过鼻内共给予提取物和灭活 A/PR8(H1N1)流感病毒血凝素(HA)疫苗,研究了菌丝体提取物的佐剂作用。在 BALB/c 小鼠中,与灭活疫苗联合使用菌丝体提取物可分别诱导鼻冲洗液和血清中高抗 A/PR8 HA 特异性 IgA 和 IgG 反应。给予疫苗与菌丝体提取物还诱导了病毒特异性细胞毒性 T 淋巴细胞反应,从而防止了致死性流感病毒 A/PR8 的肺部感染。此外,鼻内给予与香菇菌丝体提取物联合使用的 NIBRG14 疫苗可针对在鼻感染模型中异源流感 A/印度尼西亚/6/2005 病毒攻击提供交叉保护。此外,菌丝体提取物可诱导骨髓来源的树突状细胞中促炎细胞因子和 CD40 的表达。这些结果表明,菌丝体提取物佐剂疫苗可针对变异 H5N1 流感病毒提供交叉保护。建议使用从食用蘑菇中提取的菌丝体提取物作为鼻内流感病毒感染疫苗接种的新型安全有效的黏膜佐剂。

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