title: A candidate H1N1 pandemic influenza vaccine elicits protective immunity in mice.
abstract: BACKGROUND
  In 2009 a new pandemic disease appeared and spread globally. The recent emergence of the pandemic influenza virus H1N1 first isolated in Mexico and USA raised concerns about vaccine availability. We here report our development of an adenovirus-based influenza H1N1 vaccine tested for immunogenicity and efficacy to confer protection in animal model.
  
  
  METHODS
  We generated two adenovirus(Ad5)-based influenza vaccine candidates encoding the wildtype or a codon-optimized hemagglutinin antigen (HA) from the recently emerged swine influenza isolate A/California/04/2009 (H1N1)pdm. After verification of antigen expression, immunogenicity of the vaccine candidates were tested in a mouse model using dose escalations for subcutaneous immunization. Sera of immunized animals were tested in microneutalization and hemagglutination inhibition assays for the presence of HA-specific antibodies. HA-specific T-cells were measured in IFNgamma Elispot assays. The efficiency of the influenza vaccine candidates were evaluated in a challenge model by measuring viral titer in lung and nasal turbinate 3 days after inoculation of a homologous H1N1 virus.
  
  
  CONCLUSIONS
  A single immunization resulted in robust cellular and humoral immune response. Remarkably, the intensity of the immune response was substantially enhanced with codon-optimized antigen, indicating the benefit of manipulating the genetic code of HA antigens in the context of recombinant influenza vaccine design. These results highlight the value of advanced technologies in vaccine development and deployment in response to infections with pandemic potential. Our study emphasizes the potential of an adenoviral-based influenza vaccine platform with the benefits of speed of manufacture and efficacy of a single dose immunization.
authors.affiliation: Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America.
authors.forename: Julia
authors.initials: J
authors.lastname: Steitz
authors.forename: Peter G
authors.initials: PG
authors.lastname: Barlow
authors.forename: Jaber
authors.initials: J
authors.lastname: Hossain
authors.forename: Eun
authors.initials: E
authors.lastname: Kim
authors.forename: Kaori
authors.initials: K
authors.lastname: Okada
authors.forename: Tom
authors.initials: T
authors.lastname: Kenniston
authors.forename: Sheri
authors.initials: S
authors.lastname: Rea
authors.forename: Ruben O
authors.initials: RO
authors.lastname: Donis
authors.forename: Andrea
authors.initials: A
authors.lastname: Gambotto
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D004196:Disease Outbreaks; D005260:Female; D006801:Humans; D007109:Immunity / Q000276:immunology*; D007111:Immunity, Cellular; D056724:Immunity, Humoral; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000276:immunology*; D007251:Influenza, Human / Q000453:epidemiology* / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections / Q000453:epidemiology / Q000276:immunology* / Q000517:prevention & control*; D015203:Reproducibility of Results
chemical_list: D007252:Influenza Vaccines
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