Novel linear DNA vaccines induce protective immune responses against lethal infection with influenza virus type A/H5N1.
Kendirgi F, Yun NE, Linde NS, Zacks MA, Smith JN, Smith JK, McMicken H, Chen Y, Paessler S.
CytoGenix, Inc., 3100 Wilcrest Dr. Suite 140, Houston, TX 77042, USA.
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(trade mark)) to produce prototype linear DNA vaccines against the influenza virus type A/H5N1. This synDNA(trade mark) 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(trade mark)), hemagglutinin alone (H5 synDNA(trade mark)) or neuraminidase alone (N1 synDNA(trade mark)) was evaluated in mice. Two of the constructs (H5 synDNA(trade mark) and H5N1 synDNA(trade mark)) 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(trade mark) process highly suitable as alternatives to other vaccine preparations.
PMID: 18443425 [PubMed - as supplied by publisher]
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