APC targeted micelle for enhanced intradermal delivery of hepatitis B DNA vaccine

Buddhadev Layek, Lindsey Lipp, Jagdish Singh

Research output: Contribution to journalArticlepeer-review

32 Scopus citations

Abstract

Chronic hepatitis B is a serious liver disease and puts people at high risk of death from cirrhosis and liver cancer. Although DNA vaccination has been emerged as a potential immunotherapeutic strategy for the treatment of chronic hepatitis B, the efficiencies were not adequate in clinical trials. Here we describe the design, synthesis, and evaluation of mannosylated phenylalanine grafted chitosan (Man-CS-Phe) as a DNA delivery vector for direct transfection of antigen presenting cells to improve cellular and humoral immunity to plasmid-coded antigen. The cationic Man-CS-Phe micelles condense plasmid DNA into nanoscale polyplexes and provide efficient protection of complexed DNA from nuclease degradation. The mannose receptor-mediated enhanced cell uptake and high in vitro transfection efficiency of the polyplexes were demonstrated in RAW 264.7 and DC 2.4 cells using GFP-expressing plasmid DNA. Furthermore, intradermal immunization of BALB/c mice indicated that hepatitis B DNA vaccine/Man-CS-Phe polyplexes not only induced multi-fold higher serum antibody titer in comparison to all other formulations including FuGENE HD, but also significantly stimulated T-cell proliferation and skewed T helper toward Th1 polarization. These results illustrate that the Man-CS-Phe can serve as a promising DNA delivery vector to harness both cellular and humoral arms of immune system.

Original languageEnglish (US)
Pages (from-to)143-153
Number of pages11
JournalJournal of Controlled Release
Volume207
DOIs
StatePublished - Jun 10 2015

Keywords

  • Antigen presenting cells
  • Chitosan
  • DNA vaccine
  • Micelles
  • Nonviral vector
  • Transfection

Fingerprint Dive into the research topics of 'APC targeted micelle for enhanced intradermal delivery of hepatitis B DNA vaccine'. Together they form a unique fingerprint.

Cite this