PURPOSE: A plasmid-based gene expression system was complexed with protective, interactive, and non-condensing (PINC) polymer system and administered with Medi-Jector, 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 beta-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. Beta-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 beta-galactosidase expression, following i.m. injection of pCMV-betagalactosidase/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.
PURPOSE: A plasmid-based gene expression system was complexed with protective, interactive, and non-condensing (PINC) polymer system and administered with Medi-Jector, a needle-free injection device (NFID), to achieve high and sustained levels of antigen-specific antibodies in blood circulation. METHODS:Humangrowth hormone (hGH) or bacterial beta-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. Beta-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 beta-galactosidase expression, following i.m. injection of pCMV-betagalactosidase/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.
Authors: K Anwer; M Shi; M F French; S R Muller; W Chen; Q Liu; B L Proctor; J Wang; R J Mumper; A Singhal; A P Rolland; H W Alila Journal: Hum Gene Ther Date: 1998-03-20 Impact factor: 5.695
Authors: B Wang; K E Ugen; V Srikantan; M G Agadjanyan; K Dang; Y Refaeli; A I Sato; J Boyer; W V Williams; D B Weiner Journal: Proc Natl Acad Sci U S A Date: 1993-05-01 Impact factor: 11.205
Authors: E F Fynan; R G Webster; D H Fuller; J R Haynes; J C Santoro; H L Robinson Journal: Proc Natl Acad Sci U S A Date: 1993-12-15 Impact factor: 11.205
Authors: Chun-Ming Huang; Zhongkai Shi; Tivanka S DeSilva; Masato Yamamoto; Kent R Van Kampen; Craig A Elmets; De-chu C Tang Journal: Proteomics Date: 2005-03 Impact factor: 3.984
Authors: K Anwer; M Logan; F Tagliaferri; M Wadhwa; O Monera; C H Tung; W Chen; P Leonard; M French; B Proctor; E Wilson; A Singhal; A Rolland Journal: Pharm Res Date: 2000-04 Impact factor: 4.200
Authors: Geoffrey J Gorse; Mark J Newman; Allan deCamp; Christine Mhorag Hay; Stephen C De Rosa; Elizabeth Noonan; Brian D Livingston; Jonathan D Fuchs; Spyros A Kalams; Farah L Cassis-Ghavami Journal: Clin Vaccine Immunol Date: 2012-03-07