Increased immune responses in rhesus macaques by DNA vaccination combined with electroporation

Margherita Rosati, Antonio Valentin, Rashmi Jalah, Vainav Patel, Agneta von Gegerfelt, Cristina Bergamaschi, Candido Alicea, Deborah Weiss, Jim Treece, Ranajit Pal, Phillip D. Markham, Ernesto T A Marques, Thomas August, Amir Khan, Ruxandra Draghia-Akli, Barbara K. Felber, George N. Pavlakis

Research output: Contribution to journalArticle

Abstract

We used optimized DNA expression vectors to compare two gene delivery methodologies in rhesus macaques, namely direct DNA injection and in vivo adaptive constant-current electroporation via the intramuscular route. The use of in vivo electroporation increased levels of gene expression and immune responses. We used an optimized HIV gag expression plasmid to show the development of new cellular immune responses in SIV-infected animals controlling viremia. Furthermore, after vaccination with SIV expression plasmids the recall responses to the SIV antigens were very high, indicating that DNA is a strong boost in the presence of antiretroviral treatment in SIV-infected animals. There was substantial animal-to-animal variability in DNA expression, revealed by plasma measurements of IL-15 produced by co-injected IL-15 DNA. IL-15 expression levels correlated with peak immune responses. Electroporation led to an expansion of antigen-specific CD4+ and CD8+ T cells of both central and effector memory phenotype. These results indicate that improved gene delivery and expression by electroporation dramatically increases immunogenicity of DNA vaccines. Electroporation is thus an important method to improve the effectiveness of DNA vaccination.

Original languageEnglish (US)
Pages (from-to)5223-5229
Number of pages7
JournalVaccine
Volume26
Issue number40
DOIs
Publication statusPublished - Sep 19 2008

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Keywords

  • Central memory
  • DNA vaccine
  • Effector memory
  • Electroporation
  • HIV
  • Immune response
  • Intramuscular injection
  • Rhesus macaque
  • SIV
  • T cell subset

ASJC Scopus subject areas

  • Immunology
  • Microbiology
  • Virology
  • Infectious Diseases
  • Public Health, Environmental and Occupational Health
  • veterinary(all)

Cite this

Rosati, M., Valentin, A., Jalah, R., Patel, V., von Gegerfelt, A., Bergamaschi, C., ... Pavlakis, G. N. (2008). Increased immune responses in rhesus macaques by DNA vaccination combined with electroporation. Vaccine, 26(40), 5223-5229. https://doi.org/10.1016/j.vaccine.2008.03.090