Shanghai Institute of Biological Products, Shanghai 200052, China.
Biosafety Level-3 Laboratory, Key Laboratory of Medical Molecular Virology MOE &MOH, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.
Sci Rep. 2016 Jun 29;6:28729. doi: 10.1038/srep28729.
Influenza virus evolves constantly in an unpredictable fashion, making it necessary to vaccinate people annually for effective prevention and control of influenza. In general, however, during the first wave of an influenza outbreak caused by a newly emerging virus strain, influenza morbidity and mortality have been observed to rise sharply due to the lack of a matching vaccine. This necessitates the exploration of novel intervention approaches, particularly those prophylactic or therapeutic agents that have a broad range of antiviral activities and are also proven to be non-toxic. Here, we reported that stimulation of the innate immune system by intranasal administration of chitosan as a single agent was sufficient to completely protect BALB/c mice from lethal infection by H7N9 virus, a newly emerged viral strain that is highly pathogenic to humans. Remarkably, animals could still be protected against lethal challenge by H7N9 (10×LD50), even ten days after the intranasal chitosan administration. The significantly enhanced infiltration of leukocytes in the bronchoalveolar lavage and elevated levels of proinflammatory cytokines in the bronchia/lung tissues revealed the potent activation of mucosal immune responses by intranasally delivered chitosan. We also observed that chitosan can protect mice from three other virus strains. The marked breadth and magnitude of protection against diverse viral strains makes chitosan an attractive candidate as a universal anti-influenza agent.
流感病毒不断以不可预测的方式进化，因此每年都需要对人群进行疫苗接种，以有效预防和控制流感。然而，一般来说，在由新出现的病毒株引起的流感爆发的第一波中，由于缺乏匹配的疫苗，流感发病率和死亡率会急剧上升。这就需要探索新的干预方法，特别是那些具有广泛抗病毒活性且已被证明无毒的预防性或治疗性药物。在这里，我们报告称，通过鼻腔内给予壳聚糖作为单一药物刺激固有免疫系统足以完全保护 BALB/c 小鼠免受高致病性人源 H7N9 病毒的致死性感染。值得注意的是，即使在鼻腔内给予壳聚糖十天后，动物仍能免受 H7N9（10×LD50）的致死性挑战。支气管肺泡灌洗液中白细胞的显著浸润和支气管/肺组织中促炎细胞因子水平的升高表明，鼻腔内给予壳聚糖能强烈激活黏膜免疫反应。我们还观察到壳聚糖可以保护小鼠免受其他三种病毒株的侵害。壳聚糖对多种病毒株的广泛和显著保护作用使其成为一种有吸引力的通用抗流感药物候选物。
