title: Assessment of influenza virus hemagglutinin stalk-based immunity in ferrets.
abstract: Therapeutic monoclonal antibodies that target the conserved stalk domain of the influenza virus hemagglutinin and stalk-based universal influenza virus vaccine strategies are being developed as promising countermeasures for influenza virus infections. The pan-H1-reactive monoclonal antibody 6F12 has been extensively characterized and shows broad efficacy against divergent H1N1 strains in the mouse model. Here we demonstrate its efficacy against a pandemic H1N1 challenge virus in the ferret model of influenza disease. Furthermore, we recently developed a universal influenza virus vaccine strategy based on chimeric hemagglutinin constructs that focuses the immune response on the conserved stalk domain of the hemagglutinin. Here we set out to test this vaccination strategy in the ferret model. Both strategies, pretreatment of animals with a stalk-reactive monoclonal antibody and vaccination with chimeric hemagglutinin-based constructs, were able to significantly reduce viral titers in nasal turbinates, lungs, and olfactory bulbs. In addition, vaccinated animals also showed reduced nasal wash viral titers. In summary, both strategies showed efficacy in reducing viral loads after an influenza virus challenge in the ferret model.
  
  
  OBJECTIVE
  Influenza virus hemagglutinin stalk-reactive antibodies tend to be less potent yet are more broadly reactive and can neutralize seasonal and pandemic influenza virus strains. The ferret model was used to assess the potential of hemagglutinin stalk-based immunity to provide protection against influenza virus infection. The novelty and significance of the findings described in this report support the development of vaccines stimulating stalk-specific antibody responses.
authors.affiliation: Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Florian
authors.initials: F
authors.lastname: Krammer
authors.forename: Rong
authors.initials: R
authors.lastname: Hai
authors.forename: Mark
authors.initials: M
authors.lastname: Yondola
authors.forename: Gene S
authors.initials: GS
authors.lastname: Tan
authors.forename: Victor H
authors.initials: VH
authors.lastname: Leyva-Grado
authors.forename: Alex B
authors.initials: AB
authors.lastname: Ryder
authors.forename: Matthew S
authors.initials: MS
authors.lastname: Miller
authors.forename: John K
authors.initials: JK
authors.lastname: Rose
authors.forename: Peter
authors.initials: P
authors.lastname: Palese
authors.forename: Adolfo
authors.initials: A
authors.lastname: García-Sastre
authors.forename: Randy A
authors.initials: RA
authors.lastname: Albrecht
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology; D000914:Antibodies, Viral / Q000276:immunology; D004195:Disease Models, Animal; D005289:Ferrets; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000008:administration & dosage / Q000737:chemistry* / Q000235:genetics / Q000276:immunology*; D006388:Hemagglutinins; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000235:genetics / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D007251:Influenza, Human / Q000276:immunology* / Q000517:prevention & control / Q000821:virology; D008297:Male; D017434:Protein Structure, Tertiary
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D006388:Hemagglutinins; D007252:Influenza Vaccines