S. Manam et al., Plasmid DNA vaccines: Tissue distribution and effects of DNA sequence, adjuvants and delivery method on integration into host DNA, INTERVIROLO, 43(4-6), 2000, pp. 273-281
A variety of factors could affect the frequency of integration of plasmid D
NA vaccines into host cellular DNA, including DNA sequences within the plas
mid, the expressed gene product (antigen), the formulation, delivery method
, route of administration, and the type of cells exposed to the plasmid. In
this report, we examined the tissue distribution and potential integration
of plasmid DNA vaccines following intramuscular administration in mice and
guinea pigs. We compared needle versus Biojector (needleless jet) delivery
, examined the effect of aluminum phosphate adjuvants, compared the results
of different plasmid DNA vaccines, and tested a gene (the human papilloma
virus E7 gene) whose protein product is known to increase integration frequ
ency in vitro. Six weeks following intramuscular injection, the vast majori
ty of the plasmid was detected in the muscle and skin near the injection si
te; lower levels of plasmid were also detected in the draining lymph nodes.
At early time points (1-7 days) after injection, a low level of systemic e
xposure could be detected. Occasionally, plasmid was detected in gonads, bu
t it dissipated rapidly and was extrachromosomal - indicating a low risk of
germline transmission. Aluminum phosphate adjuvant had no effect on the ti
ssue distribution and did not result in a detectable increase in integratio
n frequency. Biojector delivery, compared with needle injection, greatly in
creased the uptake of plasmid (particularly in skin at the injection site),
but did not result in a detectable increase in integration frequency. Fina
lly, injection of a plasmid DNA vaccine containing the human papilloma viru
s type 16 E7 gene, known to increase integration in vitro, did not result i
n detectable integration in mice. These results suggest that the risk of in
tegration following intramuscular injection of plasmid DNA is low under a v
ariety of experimental conditions. Copyright (C) 2001 S. Karger AG, Basel.