title: Nonclinical biodistribution, integration, and toxicology evaluations of an H5N1 pandemic influenza plasmid DNA vaccine formulated with Vaxfectin®.
abstract: Vaxfectin(®) is a lipid-based adjuvant initially developed for use with plasmid DNA (pDNA) vaccines. Here we present detailed nonclinical assessments performed prior to Vaxfectin(®)'s first-in-man use, as an adjuvant in the H5N1 influenza vaccine VCL-IPT1. Following IM delivery to rabbits, VCL-IPT1 pDNA localized primarily to injection sites, where levels steadily declined over the 2 months examined. Risk of pDNA integration into genomic DNA was negligible. Toxicology studies in rabbits revealed mild inflammatory/immune responses at injection sites characteristic of IM vaccine delivery; Vaxfectin(®) directly contributed to these responses. These data support clinical development of H5N1 pDNA vaccines, and also present an encouraging profile for further development of Vaxfectin(®) as an adjuvant for vaccines in general.
authors.affiliation: Vical Incorporated, 10390 Pacific Center Court, San Diego, CA 92121-4340, USA. jdoukas@vical.com
authors.forename: John
authors.initials: J
authors.lastname: Doukas
authors.forename: Jane
authors.initials: J
authors.lastname: Morrow
authors.forename: Dawn
authors.initials: D
authors.lastname: Bellinger
authors.forename: Thomas
authors.initials: T
authors.lastname: Hilgert
authors.forename: Terrie
authors.initials: T
authors.lastname: Martin
authors.forename: Doug
authors.initials: D
authors.lastname: Jones
authors.forename: Rohit
authors.initials: R
authors.lastname: Mahajan
authors.forename: Denis
authors.initials: D
authors.lastname: Rusalov
authors.forename: Sean
authors.initials: S
authors.lastname: Sullivan
authors.forename: Alain
authors.initials: A
authors.lastname: Rolland
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D000818:Animals; D053124:Influenza A Virus, H5N1 Subtype / Q000235:genetics*; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000235:genetics / Q000493:pharmacokinetics*; D007273:Injections, Intramuscular; D008297:Male; D010714:Phosphatidylethanolamines / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D011817:Rabbits; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000009:adverse effects / Q000235:genetics / Q000493:pharmacokinetics*
chemical_list: D000276:Adjuvants, Immunologic; D007252:Influenza Vaccines; D010714:Phosphatidylethanolamines; D019444:Vaccines, DNA; C460866:vaxfectin