Nonclinical biodistribution, integration, and toxicology evaluations of an H5N1 pandemic influenza plasmid DNA vaccine formulated with Vaxfectin®

Vaccine. 2011 Jul 26;29(33):5443-52. doi: 10.1016/j.vaccine.2011.05.060. Epub 2011 Jun 17.

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.

MeSH terms

  • Adjuvants, Immunologic / administration & dosage
  • Adjuvants, Immunologic / adverse effects
  • Adjuvants, Immunologic / pharmacokinetics*
  • Animals
  • Influenza A Virus, H5N1 Subtype / genetics*
  • Influenza Vaccines / administration & dosage
  • Influenza Vaccines / adverse effects
  • Influenza Vaccines / genetics
  • Influenza Vaccines / pharmacokinetics*
  • Injections, Intramuscular
  • Male
  • Phosphatidylethanolamines / administration & dosage
  • Phosphatidylethanolamines / adverse effects
  • Phosphatidylethanolamines / pharmacokinetics*
  • Rabbits
  • Vaccines, DNA / administration & dosage
  • Vaccines, DNA / adverse effects
  • Vaccines, DNA / genetics
  • Vaccines, DNA / pharmacokinetics*

Substances

  • Adjuvants, Immunologic
  • Influenza Vaccines
  • Phosphatidylethanolamines
  • Vaccines, DNA
  • vaxfectin