title: Intranasal Administration of Chitosan Against Influenza A (H7N9) Virus Infection in a Mouse Model.
abstract: 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.
authors.affiliation: Shanghai Institute of Biological Products, Shanghai 200052, China.
authors.forename: Mei
authors.initials: M
authors.lastname: Zheng
authors.affiliation: Biosafety Level-3 Laboratory, Key Laboratory of Medical Molecular Virology MOE &MOH, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.
authors.forename: Di
authors.initials: D
authors.lastname: Qu
authors.affiliation: Shanghai Institute of Biological Products, Shanghai 200052, China.
authors.forename: Haiming
authors.initials: H
authors.lastname: Wang
authors.affiliation: Biosafety Level-3 Laboratory, Key Laboratory of Medical Molecular Virology MOE &MOH, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.
authors.forename: Zhiping
authors.initials: Z
authors.lastname: Sun
authors.affiliation: Shanghai Institute of Biological Products, Shanghai 200052, China.
authors.forename: Xueying
authors.initials: X
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, Hubei, China.
authors.forename: Jianjun
authors.initials: J
authors.lastname: Chen
authors.affiliation: National Institutes for Food and Drug Control and WHO Collaborating Center for Standardization and Evaluation of Biologicals, Beijing, China.
authors.forename: Changgui
authors.initials: C
authors.lastname: Li
authors.affiliation: Centre for Vaccine Evaluation, Biologics and Genetic Therapies Directorate, HPFB, Health Canada, Ottawa, ON, Canada.
authors.forename: Xuguang
authors.initials: X
authors.lastname: Li
authors.affiliation: Shanghai Institute of Biological Products, Shanghai 200052, China.|College of Life Sciences, Hunan Normal University, Changsha 410081, Hunan, China.
authors.forename: Ze
authors.initials: Z
authors.lastname: Chen
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D048271:Chitosan / Q000494:pharmacology*; D007113:Immunity, Innate / Q000187:drug effects*; D064766:Influenza A Virus, H7N9 Subtype / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000517:prevention & control*
chemical_list: D048271:Chitosan