title: The immune correlates of protection for an avian influenza H5N1 vaccine in the ferret model using oil-in-water adjuvants.
abstract: Because of the pathogenicity and low incidence of avian influenza virus infections in humans, the immune correlates of protection for avian influenza vaccines cannot be determined from clinical studies. Here, we used the ferret model to address this for an avian influenza H5N1 vaccine. Using oil-in-water adjuvants, we generated groups of ferrets with undetectable (geometric mean titer [GMT] < 10), low (GMT = 28.3), or high (GMT > 761.1) hemagglutination-inhibition (HAI) titers to the A/Viet Nam/1203/2004 (H5N1) virus. Ferrets were then challenged with the wild-type virus and disease severity and immunologic parameters were studied. The severity of infection and symptom profile were inversely associated with pre-challenge HAI titers in a dose-dependent manner. A vaccinated ferret with no detectable HAI-antibodies but high flu-specific IgG-antibody titers mounted rapid functional antibodies after infection and experienced milder disease compared to other ferrets in the group. Compared to naïve ferrets, all vaccinated ferrets showed improved cellular immunity in the lungs and peripheral blood. High number of IFNγ+CD8- T cells in the airways was associated with early viral clearance. Thus, while neutralizing antibodies are the best correlate of protection, non-neutralizing antibodies can also be protective. This should be taken into consideration in future avian influenza vaccine trials.
authors.affiliation: Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors.forename: Sook-San
authors.initials: SS
authors.lastname: Wong
authors.affiliation: Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors.forename: Susu
authors.initials: S
authors.lastname: Duan
authors.affiliation: Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: DeBeauchamp
authors.affiliation: Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Zanin
authors.affiliation: Animal Resource Center, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors.forename: Lisa
authors.initials: L
authors.lastname: Kercher
authors.affiliation: Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Sonnberg
authors.affiliation: Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Fabrizio
authors.affiliation: Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors.forename: Trushar
authors.initials: T
authors.lastname: Jeevan
authors.affiliation: Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors.forename: Jeri-Carol
authors.initials: JC
authors.lastname: Crumpton
authors.affiliation: Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors.forename: Christine
authors.initials: C
authors.lastname: Oshansky
authors.affiliation: Department of Biostatistics, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors.forename: Yilun
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Biostatistics, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Tang
authors.affiliation: Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Thomas
authors.affiliation: Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Webby
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D000917:Antibody Formation / Q000276:immunology; D001717:Birds / Q000821:virology*; D001992:Bronchoalveolar Lavage Fluid; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D004195:Disease Models, Animal; D005289:Ferrets / Q000276:immunology* / Q000821:virology; D006385:Hemagglutination Inhibition Tests; D007111:Immunity, Cellular; D007074:Immunoglobulin G / Q000097:blood; D053124:Influenza A Virus, H5N1 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000276:immunology*; D009821:Oils / Q000737:chemistry*; D009976:Orthomyxoviridae Infections / Q000097:blood / Q000276:immunology / Q000517:prevention & control / Q000821:virology*; D012720:Severity of Illness Index; D014611:Vaccination; D014867:Water / Q000737:chemistry*
chemical_list: D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D007074:Immunoglobulin G; D007252:Influenza Vaccines; D009821:Oils; D014867:Water