Novel linear DNA vaccines induce protective immune responses against lethal infection with influenza virus type A/H5N1

Frédéric Kendirgi, Nadezda E. Yun, Nathaniel S. Linde, Michele A. Zacks, Jeanon N. Smith, Jennifer K. Smith, Harilyn McMicken, Yin Chen, Slobodan Paessler

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

Vaccine development for possible influenza pandemics has been challenging. Conventional vaccines such as inactivated and live attenuated virus preparations are limited in terms of production speed and capacity. DNA vaccination has emerged as a potential alternative to conventional vaccines against influenza pandemics. In this study, we use a novel, cell-free DNA manufacturing process (synDNA™) to produce prototype linear DNA vaccines against the influenza virus type A/H5N1. This synDNA™ process does not require bacterial fermentation, so it avoids the use of antibiotic resistance genes and other nucleic acid sequences unrelated to the antigen gene expression in the actual therapeutic DNA construct. The efficacy of various vaccines expressing the hemagglutinin and neuraminidase proteins (H5N1 synDNA™), hemagglutinin alone (H5 synDNA™) or neuraminidase alone (N1 synDNA™) was evaluated in mice. Two of the constructs (H5 synDNA™ and H5N1 synDNA™) induced a robust protective immune response with up to 93% of treated mice surviving a lethal challenge of a virulent influenza A/Vietnam/1203/04 H5N1 isolate. In combination with a potent biological activity and simplified production footprint, these characteristics make DNA vaccines prepared with our synDNA™ process highly suitable as alternatives to other vaccine preparations.

Original languageEnglish (US)
Pages (from-to)410-419
Number of pages10
JournalHuman Vaccines
Volume4
Issue number6
DOIs
StatePublished - Jan 1 2008

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Keywords

  • Cell-free DNA vaccine production
  • DNA vaccine
  • Immune response
  • Influenza virus type A/H5N1
  • SynDNA™ vaccine

ASJC Scopus subject areas

  • Immunology
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

Kendirgi, F., Yun, N. E., Linde, N. S., Zacks, M. A., Smith, J. N., Smith, J. K., McMicken, H., Chen, Y., & Paessler, S. (2008). Novel linear DNA vaccines induce protective immune responses against lethal infection with influenza virus type A/H5N1. Human Vaccines, 4(6), 410-419. https://doi.org/10.4161/hv.4.6.6177