Plasmid DNA malaria vaccine: Tissue distribution and safety studies in mice and rabbits

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.