Purpose. A plasmid-based gene expression system was complexed with protecti
ve, interactive, and non-condensing (PINC(TM)) polymer system and administe
red with Medi-Jector(TM), a needle-free injection device (NFID), to achieve
high and sustained levels of antigen-specific antibodies in blood circulat
ion.
Methods. Human growth hormone (hGH) or bacterial beta-galactosidase gene ex
pression plasmids driven by a cytomegalovirus (CMV) promoter were formulate
d in saline or complexed with a PINC polymer, polyvinylpyrrolidone (PVP), a
nd intramuscularly or subcutaneously administered into dogs and pigs using
a 22-gauge needle or a NFID. The hGH-specific IgG titers in serum were meas
ured by an ELISA. beta-galactosidase expression was measured in injected mu
scles 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 exp
ression 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 injecti
on, pDNA delivery by a NFID was superior to pDNA injection by needle. The m
agnitude of hGH-specific IgG titers with NFID was 15-20-fold higher than ne
edle injection when pDNA was complexed with PVP, and only 3-4-fold higher w
ith pDNA in saline. The transfection efficiency in the injected muscle, as
measured by beta-galactosidase expression, following i.m. injection of pCMV
-beta-galactosidase/PVP, was not significantly different between needle and
NFID-injected groups.
Conclusions. These data demonstrate that the combination of pDNA/PVP comple
xes and a NFID act synergistically to achieve high and sustained levels of
antigen-specific IgG response to expressed antigen. This gene delivery appr
oach may offer advantage over needle injection of naked DNA for the develop
ment of genetic vaccines.