Intramuscular immunization with a monogenic plasmid DNA tuberculosis vaccine: Enhanced immunogenicity by electroporation and co-expression of GM-CSF transgene

Xizhong Zhang, Maziar Divangahi, Patricia Ngai, Michael Santosuosso, James Millar, Anna Zganiacz, Jun Wang, Jonathan Bramson, Zhou Xing

Research output: Contribution to journalArticlepeer-review

61 Citations (Scopus)

Abstract

Plasmid DNA vaccine has been widely explored for tuberculosis immunization but there is a need to develop the ways to improve its immunogenicity. In this study, we have constructed a plasmid DNA vaccine coding for Ag85A alone or for both Ag85A and GM-CSF and investigated the immune adjuvant effects of electroporation and GM-CSF co-expression, alone or in combination, on CD4 and CD8 T cell IFN-γ responses, CTL activities and immune protection from pulmonary Mycobacterium tuberculosis challenge in a Balb/c mouse model. We have found that use of electroporation allows a single intramuscular (i.m.) DNA injection to be as effective as repeated i.m. DNA injections in activation of both Ag85A-specific CD4 and CD8 T cells. Co-expression of immune-enhancing cytokine GM-CSF by the same plasmid DNA TB vaccine could further enhance T cell activation including CTL activities on top of electroporation. With regard to immune protection from pulmonary M. tb challenge, use of eletroporation also allows a single i.m. DNA injection to be as effective as repeated i.m. DNA injections. Co-expression of GM-CSF transgene also moderately enhances immune protection and such effect is more evident for systemic protection. However, GM-CSF expression has little added effect on immune protection by electroporation-aided immunization protocols. Our findings thus will help with the development of future DNA TB immunization strategies.

Original languageEnglish
Pages (from-to)1342-1352
Number of pages11
JournalVaccine
Volume25
Issue number7
DOIs
Publication statusPublished - Jan 26 2007
Externally publishedYes

Bibliographical note

Funding Information:
We thank the helpful technical advice provided by Dr. Linming Liu and Tony Yang. We are also grateful to the provision of M. tb genomic DNA and Ag85 complex proteins by Colorado State University through the funds from the NIH. This study is supported by funds from the Canadian Institutes of Health Research.

ASJC Scopus Subject Areas

  • Molecular Medicine
  • General Immunology and Microbiology
  • General Veterinary
  • Public Health, Environmental and Occupational Health
  • Infectious Diseases

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