title: Treatment with anti-C5a antibody improves the outcome of H7N9 virus infection in African green monkeys.
abstract: BACKGROUND
  Patients infected with influenza A(H7N9) virus present with acute lung injury (ALI) that is due to severe pneumonia and systemic inflammation. It is often fatal because there are few effective treatment options. Complement activation has been implicated in the pathogenesis of virus-induced lung injury; therefore, we investigated the effect of targeted complement inhibition on ALI induced by H7N9 virus infection.
  
  
  METHODS
  A novel neutralizing specific antihuman C5a antibody (IFX-1) was used. This antibody blocked the ability of C5a to induce granulocytes to express CD11b while not affecting the ability of C5b to form the membrane attack complex. African green monkeys were inoculated with H7N9 virus and treated intravenously with IFX-1.
  
  
  RESULTS
  The virus infection led to intense ALI and systemic inflammatory response syndrome (SIRS) in association with excessive complement activation. Anti-C5a treatment in H7N9-infected monkeys substantially attenuated ALI: It markedly reduced the lung histopathological injury and decreased the lung infiltration of macrophages and neutrophils. Moreover, the treatment decreased the intensity of SIRS; the body temperature changes were minimal and the plasma levels of inflammatory mediators were markedly reduced. The treatments also significantly decreased the virus titers in the infected lungs.
  
  
  CONCLUSIONS
  Antihuman C5a antibody treatment remarkably reduced the ALI and systemic inflammation induced by H7N9 virus infection. Complement inhibition may be a promising adjunctive therapy for severe viral pneumonia.
authors.affiliation: State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology.
authors.forename: Shihui
authors.initials: S
authors.lastname: Sun
authors.affiliation: State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology.
authors.forename: Guangyu
authors.initials: G
authors.lastname: Zhao
authors.affiliation: State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology.
authors.forename: Chenfeng
authors.initials: C
authors.lastname: Liu
authors.affiliation: Laboratory Animal Center, Academy of Military Medical Science.
authors.forename: Wei
authors.initials: W
authors.lastname: Fan
authors.affiliation: Laboratory Animal Center, Academy of Military Medical Science.
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Laboratory Animal Center, Academy of Military Medical Science.
authors.forename: Lin
authors.initials: L
authors.lastname: Zeng
authors.affiliation: State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology.
authors.forename: Yan
authors.initials: Y
authors.lastname: Guo
authors.affiliation: State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology.
authors.forename: Zhihua
authors.initials: Z
authors.lastname: Kou
authors.affiliation: State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology.
authors.forename: Hong
authors.initials: H
authors.lastname: Yu
authors.affiliation: State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology.
authors.forename: Junfeng
authors.initials: J
authors.lastname: Li
authors.affiliation: Laboratory of Immunology, Beijing Institute of Basic Medical Sciences, China.
authors.forename: Renxi
authors.initials: R
authors.lastname: Wang
authors.affiliation: Laboratory of Immunology, Beijing Institute of Basic Medical Sciences, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: InflaRx GmbH, Jena, Germany.
authors.forename: Conny
authors.initials: C
authors.lastname: Schneider
authors.affiliation: InflaRx GmbH, Jena, Germany.
authors.forename: Maria
authors.initials: M
authors.lastname: Habel
authors.affiliation: InflaRx GmbH, Jena, Germany.
authors.forename: Niels C
authors.initials: NC
authors.lastname: Riedemann
authors.affiliation: Lindsley F. Kimball Research Institute, New York Blood Center, New York.
authors.forename: Lanying
authors.initials: L
authors.lastname: Du
authors.affiliation: Lindsley F. Kimball Research Institute, New York Blood Center, New York Key Laboratory of Medical Molecular Virology of Ministries of Education and Health, Shanghai Medical College, Fudan University, China.
authors.forename: Shibo
authors.initials: S
authors.lastname: Jiang
authors.affiliation: InflaRx GmbH, Jena, Germany.
authors.forename: Renfeng
authors.initials: R
authors.lastname: Guo
authors.affiliation: State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology.
authors.forename: Yusen
authors.initials: Y
authors.lastname: Zhou
mesh_terms: D055371:Acute Lung Injury / Q000276:immunology / Q000473:pathology / Q000628:therapy / Q000821:virology; D000818:Animals; D057134:Antibodies, Neutralizing / Q000627:therapeutic use*; D001831:Body Temperature; D002522:Chlorocebus aethiops / Q000821:virology; D003167:Complement Activation; D015936:Complement C5a / Q000037:antagonists & inhibitors* / Q000276:immunology*; D004195:Disease Models, Animal; D006801:Humans; D064766:Influenza A Virus, H7N9 Subtype / Q000302:isolation & purification / Q000472:pathogenicity; D007251:Influenza, Human / Q000276:immunology / Q000473:pathology / Q000628:therapy* / Q000821:virology; D008168:Lung / Q000473:pathology / Q000821:virology; D016676:Macrophages, Alveolar / Q000276:immunology; D009504:Neutrophils / Q000276:immunology; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000473:pathology / Q000628:therapy / Q000821:virology; D011024:Pneumonia, Viral / Q000276:immunology / Q000473:pathology / Q000628:therapy* / Q000821:virology; D018746:Systemic Inflammatory Response Syndrome / Q000473:pathology / Q000628:therapy / Q000821:virology; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D057134:Antibodies, Neutralizing; D015936:Complement C5a
keywords: African green monkey; H7N9; anti-C5a antibody; complement inhibition; lung injury