Synergistic effect of formulated plasmid and needle-free injection for genetic vaccines

Khursheed Anwer, Keith A. Earle, Mei Shi, Jijun Wang, Russell J. Mumper, Belinda Proctor, Kimberly Jansa, Harry C. Ledebur, Stephen Davis, William Eaglstein, Alain P. Rolland

Research output: Contribution to journalArticle

41 Scopus citations

Abstract

Purpose. A plasmid-based gene expression system was complexed with protective, interactive, and non-condensing (PINC(TM)) polymer system and administered with Medi-Jector(TM), a needle-free injection device (NFID), to achieve high and sustained levels of antigen-specific antibodies in blood circulation. Methods. Human growth hormone (hGH) or bacterial β- galactosidase gene expression plasmids driven by a cytomegalovirus (CMV) promoter were formulated in saline or complexed with a PINC polymer, polyvinylpyrrolidone (PVP), and intramuscularly or subcutaneously administered into dogs and pigs using a 22-gauge needle or a NFID. The hGH- specific IgG titers in serum were measured by an ELISA. β-galactosidase expression was measured in injected muscles by an enzymatic assay or immunohistochemistry. The effect of NFID on DNA stability and topology was assessed by gel electrophoresis. Results. Intramuscular (i.m.) or subcutaneous (s.c.) injection of a hGH expression plasmid pCMV-hGH (0.05-0.5 mg/kg) in dogs and pigs elicited antigen-specific IgG antibody titers to expressed hGH. With both routes of injection, pDNA delivery by a NFID was superior to pDNA injection by needle. The magnitude of hGH-specific IgG titers with NFID was 15-20-fold higher than needle injection when pDNA was complexed with PVP, and only 3-4-fold higher with pDNA in saline. The transfection efficiency in the injected muscle, as measured by β- galactosidase expression, following i.m. injection of pCMV-β- galactosidase/PVP, was not significantly different between needle and NFID- injected groups. Conclusions. These data demonstrate that the combination of pDNA/PVP complexes and a NFID act synergistically to achieve high and sustained levels of antigen-specific IgG response to expressed antigen. This gene delivery approach may offer advantage over needle injection of naked DNA for the development of genetic vaccines.

Original languageEnglish (US)
Pages (from-to)889-895
Number of pages7
JournalPharmaceutical Research
Volume16
Issue number6
DOIs
StatePublished - Jun 30 1999

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Keywords

  • And needle-free injection device
  • Genetic vaccines
  • Growth hormone
  • Immune response
  • Muscle
  • Polyvinylpyrrolidone

ASJC Scopus subject areas

  • Chemistry(all)
  • Pharmaceutical Science
  • Pharmacology

Cite this

Anwer, K., Earle, K. A., Shi, M., Wang, J., Mumper, R. J., Proctor, B., Jansa, K., Ledebur, H. C., Davis, S., Eaglstein, W., & Rolland, A. P. (1999). Synergistic effect of formulated plasmid and needle-free injection for genetic vaccines. Pharmaceutical Research, 16(6), 889-895. https://doi.org/10.1023/A:1018834305079