title: Comparison of the effectiveness of antibody and cell-mediated immunity against inhaled and instilled influenza virus challenge.
abstract: BACKGROUND
  To evaluate immunity against influenza, mouse challenge studies are typically performed by intranasal instillation of a virus suspension to anesthetized animals. This results in an unnatural environment in the lower respiratory tract during infection, and therefore there is some concern that immune mechanisms identified in this model may not reflect those that protect against infectious virus particles delivered directly to the lower respiratory tract as an aerosol.
  
  
  METHODS
  To evaluate differences in protection against instilled and inhaled virus, mice were immunized with influenza antigens known to induce antibody or cell-mediated responses and then challenged with 100 LD50 A/PR/8/34 (PR8) in the form of aerosol (inhaled) or liquid suspension (instilled).
  
  
  RESULTS
  Mice immunized with recombinant adenovirus (Ad) expressing hemagglutinin were protected against weight loss and death in both challenge models, however immunization with Ad expressing nucleoprotein of influenza A (NPA) or M2 resulted in greater protection against inhaled aerosolized virus than virus instilled in liquid suspension. Ad-M2, but not Ad-NPA-immunized mice were protected against a lower instillation challenge dose.
  
  
  CONCLUSIONS
  These results demonstrate differences in protection that are dependent on challenge method, and suggest that cell-mediated immunity may be more accurately demonstrated in mouse inhalation studies. Furthermore, the data suggest immune mechanisms generally characterized as incomplete or weak in mouse models using liquid intranasal challenge may offer greater immunity against influenza infection than previously thought.
authors.affiliation: Division of Viral Products, OVRR, CBER, FDA, 8800 Rockville Pike, Building 29A 1D24, Bethesda, MD 20892, USA.
authors.forename: Katie
authors.initials: K
authors.lastname: Rivers
authors.forename: Larry E
authors.initials: LE
authors.lastname: Bowen
authors.forename: Jin
authors.initials: J
authors.lastname: Gao
authors.forename: Kevin
authors.initials: K
authors.lastname: Yang
authors.forename: John E
authors.initials: JE
authors.lastname: Trombley
authors.forename: J Kyle
authors.initials: JK
authors.lastname: Bohannon
authors.forename: Maryna C
authors.initials: MC
authors.lastname: Eichelberger
mesh_terms: D000336:Aerosols / Q000008:administration & dosage*; D000818:Animals; D001835:Body Weight; D002642:Chick Embryo; D004195:Disease Models, Animal; D005260:Female; D007111:Immunity, Cellular; D056724:Immunity, Humoral; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections / Q000276:immunology*; D011024:Pneumonia, Viral / Q000276:immunology*; D016019:Survival Analysis
chemical_list: D000336:Aerosols; D007252:Influenza Vaccines