title: Novel linear DNA vaccines induce protective immune responses against lethal infection with influenza virus type A/H5N1.
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.
authors.affiliation: CytoGenix, Inc., Houston, Texas 77042, USA.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Kendirgi
authors.forename: Nadezda E
authors.initials: NE
authors.lastname: Yun
authors.forename: Nathaniel S
authors.initials: NS
authors.lastname: Linde
authors.forename: Michele A
authors.initials: MA
authors.lastname: Zacks
authors.forename: Jeanon N
authors.initials: JN
authors.lastname: Smith
authors.forename: Jennifer K
authors.initials: JK
authors.lastname: Smith
authors.forename: Harilyn
authors.initials: H
authors.lastname: McMicken
authors.forename: Yin
authors.initials: Y
authors.lastname: Chen
authors.forename: Slobodan
authors.initials: S
authors.lastname: Paessler
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D001831:Body Temperature; D001835:Body Weight; D004797:Enzyme-Linked Immunosorbent Assay; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000276:immunology; D053124:Influenza A Virus, H5N1 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000138:chemical synthesis* / Q000276:immunology*; D051379:Mice; D009439:Neuraminidase / Q000276:immunology; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000517:prevention & control*; D016019:Survival Analysis; D019444:Vaccines, DNA / Q000138:chemical synthesis* / Q000276:immunology*; D014764:Viral Proteins / Q000276:immunology
chemical_list: D000914:Antibodies, Viral; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines; D019444:Vaccines, DNA; D014764:Viral Proteins; C109963:hemagglutinin, avian influenza A virus; C487630:NA protein, influenza A virus; D009439:Neuraminidase