Immunogenicity and Biodistribution of Anthrax DNA Vaccine Delivered by Intradermal Electroporation

Curr Drug Deliv. 2020;17(5):414-421. doi: 10.2174/1567201817666200414144550.

Abstract

Purpose: Anthrax is a lethal bacterial disease caused by gram-positive bacterium Bacillus anthracis and vaccination is a desirable method to prevent anthrax infections. In the present study, DNA vaccine encoding a protective antigen of Bacillus anthracis was prepared and we investigated the influence of DNA electrotransfer in the skin on the induced immune response and biodistribution.

Methods and results: The tdTomato reporter gene for the whole animal in vivo imaging was used to assess gene transfer efficiency into the skin as a function of electrical parameters. Compared to that with 25 V, the transgene expression of red fluorescent protein increased significantly when a voltage of 90 V was used. Delivery of DNA vaccines expressing Bacillus anthracis protective antigen domain 4 (PAD4) with an applied voltage of 90 V induced robust PA-D4-specific antibody responses. In addition, the in vivo fate of anthrax DNA vaccine was studied after intradermal administration into the mouse. DNA plasmids remained at the skin injection site for an appropriate period of time after immunization. Intradermal administration of DNA vaccine resulted in detection in various organs (viz., lung, heart, kidney, spleen, brain, and liver), although the levels were significantly reduced.

Conclusion: Our results offer important insights into how anthrax DNA vaccine delivery by intradermal electroporation affects the immune response and biodistribution of DNA vaccine. Therefore, it may provide valuable information for the development of effective DNA vaccines against anthrax infection.

Keywords: Anthrax; DNA vaccine; biodistribution; electroporation; immune response; skin delivery..

MeSH terms

  • Animals
  • Anthrax Vaccines / administration & dosage*
  • Anthrax Vaccines / pharmacokinetics
  • Antibodies, Bacterial / blood
  • Antigens, Bacterial / immunology
  • Bacillus anthracis / immunology
  • Bacterial Toxins / immunology
  • Electroporation
  • Female
  • Gene Expression
  • Genes, Reporter
  • Immunoglobulin G / blood
  • Injections, Intradermal
  • Luminescent Proteins / genetics
  • Mice, Inbred BALB C
  • Plasmids
  • Red Fluorescent Protein
  • Skin / metabolism
  • Tissue Distribution
  • Vaccines, DNA / administration & dosage*
  • Vaccines, DNA / pharmacokinetics

Substances

  • Anthrax Vaccines
  • Antibodies, Bacterial
  • Antigens, Bacterial
  • Bacterial Toxins
  • Immunoglobulin G
  • Luminescent Proteins
  • Vaccines, DNA
  • anthrax toxin