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).
Abstract
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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Details
| Item Type: |
Article
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| Status: |
Published |
| Creators/Authors: |
| Creators | Email | Pitt Username | ORCID  |
|---|
| Loudon, PT | | | | | Yager, EJ | | | | | Lynch, DT | | | | | Narendran, A | | | | | Stagnar, C | | | | | Franchini, AM | | | | | Fuller, JT | | | | | White, PA | | | | | Nyuandi, J | | | | | Wiley, CA | wiley1@pitt.edu | WILEY1 | | | Murphey-Corb, M | | | | | Fuller, DH | | | |
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| Contributors: |
| Contribution | Contributors Name | Email | Pitt Username | ORCID |
|---|
| Editor | Sandberg, Johan K. | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED |
|
| 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 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/13368 |
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