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GM-CSF increases mucosal and systemic immunogenicity of an H1N1 influenza DNA vaccine administered into the epidermis of non-human primates

Loudon, PT and Yager, EJ and Lynch, DT and Narendran, A and Stagnar, C and Franchini, AM and Fuller, JT and White, PA and Nyuandi, J and Wiley, CA and Murphey-Corb, M and Fuller, DH (2010) GM-CSF increases mucosal and systemic immunogenicity of an H1N1 influenza DNA vaccine administered into the epidermis of non-human primates. PLoS ONE, 5 (6).

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Background: The recent H5N1 avian and H1N1 swine-origin influenza virus outbreaks reaffirm that the threat of a worldwide 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. Methodology/Principal Findings: Macaques were immunized at weeks 0, 8, and 16 using a disposable single-shot particlemediated 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/Significance: 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 skindelivered GM-CSF to serve as an effective mucosal adjuvant for vaccine induction of immune responses in the gut and respiratory tract. © 2010 Loudon et al.


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Item Type: Article
Status: Published
CreatorsEmailPitt UsernameORCID
Loudon, PT
Yager, EJ
Lynch, DT
Narendran, A
Stagnar, C
Franchini, AM
Fuller, JT
White, PA
Nyuandi, J
Wiley, CAwiley1@pitt.eduWILEY1
Murphey-Corb, M
Fuller, DH
ContributionContributors NameEmailPitt UsernameORCID
Date: 9 August 2010
Date Type: Publication
Journal or Publication Title: PLoS ONE
Volume: 5
Number: 6
DOI or Unique Handle: 10.1371/journal.pone.0011021
Refereed: Yes
MeSH Headings: Adjuvants, Immunologic--pharmacology; Animals; Antibodies, Viral--biosynthesis; Antibodies, Viral--blood; Epidermis--immunology; Granulocyte-Macrophage Colony-Stimulating Factor--pharmacology; Immunity, Cellular--drug effects; Influenza A Virus, H1N1 Subtype--immunology; Macaca mulatta; Mucous Membrane--drug effects; T-Lymphocytes--immunology; Vaccines, DNA--administration & dosage; Vaccines, DNA--immunology
Other ID: NLM PMC2882341
PubMed Central ID: PMC2882341
PubMed ID: 20544035
Date Deposited: 03 Aug 2012 21:02
Last Modified: 02 Feb 2019 16:57


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