title: H5N1 whole-virus vaccine induces neutralizing antibodies in humans which are protective in a mouse passive transfer model.
abstract: BACKGROUND
  Vero cell culture-derived whole-virus H5N1 vaccines have been extensively tested in clinical trials and consistently demonstrated to be safe and immunogenic; however, clinical efficacy is difficult to evaluate in the absence of wide-spread human disease. A lethal mouse model has been utilized which allows investigation of the protective efficacy of active vaccination or passive transfer of vaccine induced sera following lethal H5N1 challenge.
  
  
  METHODS
  We used passive transfer of immune sera to investigate antibody-mediated protection elicited by a Vero cell-derived, non-adjuvanted inactivated whole-virus H5N1 vaccine. Mice were injected intravenously with H5N1 vaccine-induced rodent or human immune sera and subsequently challenged with a lethal dose of wild-type H5N1 virus.
  
  
  RESULTS
  Passive transfer of H5N1 vaccine-induced mouse, guinea pig and human immune sera provided dose-dependent protection of recipient mice against lethal challenge with wild-type H5N1 virus. Protective dose fifty values for serum H5N1 neutralizing antibody titers were calculated to be ≤1∶11 for all immune sera, independently of source species.
  
  
  CONCLUSIONS
  These data underpin the confidence that the Vero cell culture-derived, whole-virus H5N1 vaccine will be effective in a pandemic situation and support the use of neutralizing serum antibody titers as a correlate of protection for H5N1 vaccines.
authors.affiliation: Vaccine Research and Development, Baxter BioScience, Orth/Donau, Austria. keith_howard@baxter.com
authors.forename: M Keith
authors.initials: MK
authors.lastname: Howard
authors.forename: Nicolas
authors.initials: N
authors.lastname: Sabarth
authors.forename: Helga
authors.initials: H
authors.lastname: Savidis-Dacho
authors.forename: Daniel
authors.initials: D
authors.lastname: Portsmouth
authors.forename: Otfried
authors.initials: O
authors.lastname: Kistner
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Kreil
authors.forename: Hartmut J
authors.initials: HJ
authors.lastname: Ehrlich
authors.forename: P Noel
authors.initials: PN
authors.lastname: Barrett
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood / Q000276:immunology*; D004306:Dose-Response Relationship, Immunologic; D006801:Humans; D007106:Immune Sera / Q000276:immunology; D007116:Immunization, Passive; D053124:Influenza A Virus, H5N1 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000276:immunology*; D007251:Influenza, Human / Q000276:immunology / Q000821:virology; D051379:Mice; D018448:Models, Immunological; D009976:Orthomyxoviridae Infections / Q000276:immunology* / Q000517:prevention & control* / Q000821:virology; D016019:Survival Analysis; D017186:Titrimetry
chemical_list: D057134:Antibodies, Neutralizing; D007106:Immune Sera; D007252:Influenza Vaccines