Journal
HUMAN VACCINES
Volume 2, Issue 3, Pages 113-118Publisher
LANDES BIOSCIENCE
DOI: 10.4161/hv.2836
Keywords
plasmid-based vaccines; biodistribution; pharmacokinetics; real-time PCR; injection volume; cationic lipid formulation; Anthrax vaccine
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Funding
- NIAID NIH HHS [2R44 AI53060-02] Funding Source: Medline
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Experiments were conducted with a cationic lipid-formulated pDNA vaccine (VCL-AB01) to evaluate the models used to determine biodistribution, persistence and the potential for integration (into genomic DNA) of plasmid DNA-based vaccines. Mice were injected with a high-dose volume of 50 mu L unilaterally containing similar to 1.33 x 10(13) plasmid copy numbers (PCN) or a low-dose volume of 20 mu L bilaterally (-5.3 x 10(12) PCN). Rabbits were injected bilaterally with a 0.5 mL (similar to 1.33 x 10(14) PCN) volume. Injection site muscle tissue was harvested two days, one month, and two months postinjection for the low-dose murine and rabbit models and two days and two months postinjection for the high-dose murine model. Total DNA was extracted and analyzed by real-time quantitative PCR for sequences specific to the injected pDNA. The geometric mean PCN/mu g of total DNA from the high and low dose models were compared to determine if injection volume impacts clearance and/or persistence. Results from these studies showed that PCN clearance over two months was similar in mice injected with 20 mu L and rabbits injected with 0.5 mL, but PCN clearance was slower in mice injected with similar PCN in 50 mu L (1.33 x 10(13) PCN) compared to 20 mu L (5.3 x 10(12) PCN). Persistence at two months in the rabbit and low-dose murine models was comparable, with geometric mean of 5.22 X 10(3) PCN/mu g of total DNA for the low-dose volume murine model and 2.81 X 10(3)/mu g DNA for the rabbit model. Interanimal variability in persistence was not impacted by dose volume.
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