To evaluate the safety of a plasmid DNA vaccine, tissue distribution studie
s in mice and safety studies in mice and rabbits were conducted with VCL-25
10, a plasmid DNA encoding the gene for the malaria circumsporozoite protei
n from Plasmodium falciparum (PfCSP). After intramuscular administration, V
CL-2510 plasmid DNA was detected initially in all of the highly vascularize
d tissues, but at later time points was found primarily in the muscle at th
e site of injection, where it persisted for up to 8 weeks. After intravenou
s administration, plasmid DNA initially distributed at a relatively low fre
quency to all the tissues examined except the gonads and brain. However, pl
asmid DNA rapidly cleared, and by 4 weeks postadministration could be detec
ted only in the lung of one of six animals evaluated. In a safety study in
mice, eight repeated intramuscular injections of VCL-2510 at plasmid DNA do
ses of 1, 10, and 100 mu g had no adverse effects on clinical chemistry or
hematology, and did not result in any organ pathology or systemic toxicity.
In a safety study in rabbits, six repeated intramuscular injections of VCL
-2510 at plasmid DNA doses of 0.15 and 0.45 mg had no discernible effects o
n clinical chemistry, hematology, or histopathology, No evidence of autoimm
une-mediated pathology, anti-nuclear antibodies (ANA), or antibodies to dsD
NA were observed in the mouse or rabbit studies.