title: Specific polyclonal F(ab')2 neutralize a large panel of highly pathogenic avian influenza A viruses (H5N1) and control infection in mice.
abstract: OBJECTIVE
  There is still no specific therapy for infection with the highly pathogenic avian influenza A virus (HPAI) H5N1, which caused 39 human cases with a 64% fatality rate in 2013.
  
  
  METHODS
  We prepared highly purified specific equine polyclonal immunoglobulin fragments (F(ab')2) against H5N1 and tested them for efficacy in vitro and with different administration schedules in H5N1-challenged BALB/c mice.
  
  
  RESULTS
  in vitro, F(ab')2 neutralized 21 different H5N1 strains from different areas, representative of 11 different clades and sub-clades and 9 years of evolution of the virus. In vivo mouse experiments identified that the most efficient administration protocol consists of five consecutive daily injections after infection; 10 mg/kg giving a 60% increase in survival.
  
  
  CONCLUSIONS
  These data demonstrate the ability of anti-H5N1 F(ab')2 to markedly reduce the mortality and morbidity associated with infection of mice with HPAI H5N1 virus, and their potential for human therapy.
authors.affiliation: Fab'entech, Lyon, France. cecile.herbreteau-delale@fabentech.com.
authors.forename: Cécile Hélène
authors.initials: CH
authors.lastname: Herbreteau
authors.forename: Frédéric
authors.initials: F
authors.lastname: Jacquot
authors.forename: Sareth
authors.initials: S
authors.lastname: Rith
authors.forename: Laurent
authors.initials: L
authors.lastname: Vacher
authors.forename: Ludovic
authors.initials: L
authors.lastname: Nguyen
authors.forename: Caroline
authors.initials: C
authors.lastname: Carbonnelle
authors.forename: Vincent
authors.initials: V
authors.lastname: Lotteau
authors.forename: Michel
authors.initials: M
authors.lastname: Jolivet
authors.forename: Hervé
authors.initials: H
authors.lastname: Raoul
authors.forename: Philippe
authors.initials: P
authors.lastname: Buchy
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Saluzzo
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000276:immunology / Q000494:pharmacology; D057134:Antibodies, Neutralizing / Q000008:administration & dosage / Q000276:immunology / Q000494:pharmacology; D001717:Birds; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D006736:Horses; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000008:administration & dosage / Q000276:immunology* / Q000494:pharmacology; D053124:Influenza A Virus, H5N1 Subtype / Q000145:classification / Q000235:genetics / Q000276:immunology*; D005585:Influenza in Birds / Q000188:drug therapy / Q000276:immunology* / Q000401:mortality; D007274:Injections, Intraperitoneal; D061985:Madin Darby Canine Kidney Cells; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections / Q000188:drug therapy / Q000276:immunology* / Q000401:mortality; D010802:Phylogeny; D013045:Species Specificity; D016019:Survival Analysis; D015996:Survival Rate; D013997:Time Factors
chemical_list: D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D007140:Immunoglobulin Fab Fragments
keywords: F(ab’)2; Fabenflu®; H5N1; immunoglobulin; influenza; passive immunotherapy