title: GM-CSF increases mucosal and systemic immunogenicity of an H1N1 influenza DNA vaccine administered into the epidermis of non-human primates.
abstract: BACKGROUND
  The recent H5N1 avian and H1N1 swine-origin influenza virus outbreaks reaffirm that the threat of a world-wide influenza pandemic is both real and ever-present. Vaccination is still considered the best strategy for protection against influenza virus infection but a significant challenge is to identify new vaccine approaches that offer accelerated production, broader protection against drifted and shifted strains, and the capacity to elicit anti-viral immune responses in the respiratory tract at the site of viral entry. As a safe alternative to live attenuated vaccines, the mucosal and systemic immunogenicity of an H1N1 influenza (A/New Caledonia/20/99) HA DNA vaccine administered by particle-mediated epidermal delivery (PMED or gene gun) was analyzed in rhesus macaques.
  
  
  RESULTS
  Macaques were immunized at weeks 0, 8, and 16 using a disposable single-shot particle-mediated delivery device designed for clinical use that delivers plasmid DNA directly into cells of the epidermis. Significant levels of hemagglutination inhibiting (HI) antibodies and cytokine-secreting HA-specific T cells were observed in the periphery of macaques following 1-3 doses of the PMED HA DNA vaccine. In addition, HA DNA vaccination induced detectable levels of HA-specific mucosal antibodies and T cells in the lung and gut-associated lymphoid tissues of vaccinated macaques. Importantly, co-delivery of a DNA encoding the rhesus macaque GM-CSF gene was found to significantly enhance both the systemic and mucosal immunogenicity of the HA DNA vaccine.
  
  
  CONCLUSIONS
  These results provide strong support for the development of a particle-mediated epidermal DNA vaccine for protection against respiratory pathogens such as influenza and demonstrate, for the first time, the ability of skin-delivered GM-CSF to serve as an effective mucosal adjuvant for vaccine induction of immune responses in the gut and respiratory tract.
authors.affiliation: PowderMed Ltd., Oxford, UK.
authors.forename: Peter T
authors.initials: PT
authors.lastname: Loudon
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Yager
authors.forename: Debbie T
authors.initials: DT
authors.lastname: Lynch
authors.forename: Amithi
authors.initials: A
authors.lastname: Narendran
authors.forename: Cristy
authors.initials: C
authors.lastname: Stagnar
authors.forename: Anthony M
authors.initials: AM
authors.lastname: Franchini
authors.forename: James T
authors.initials: JT
authors.lastname: Fuller
authors.forename: Phil A
authors.initials: PA
authors.lastname: White
authors.forename: Julia
authors.initials: J
authors.lastname: Nyuandi
authors.forename: Clayton A
authors.initials: CA
authors.lastname: Wiley
authors.forename: Michael
authors.initials: M
authors.lastname: Murphey-Corb
authors.forename: Deborah H
authors.initials: DH
authors.lastname: Fuller
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis* / Q000097:blood; D004817:Epidermis / Q000276:immunology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D007111:Immunity, Cellular / Q000187:drug effects; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D008253:Macaca mulatta; D009092:Mucous Membrane / Q000187:drug effects*; D013601:T-Lymphocytes / Q000276:immunology; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D019444:Vaccines, DNA; D016178:Granulocyte-Macrophage Colony-Stimulating Factor