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Research Paper
Comparison of Rabbit and Mouse Models for Persistence Analysis of Plasmid-Based Vaccines
Vicky L. Leamy, Terrie Martin, Rohit Mahajan, Adrian Vilalta, Denis Rusalov, Jukka Hartikka, Vesselina Bozoukova, Keith D. Hall, Jane Morrow, Alain P. Rolland, David C. Kaslow and Peggy A. Lalor
volume 2 | issue 3
may/june 2006Pages: 113 - 118
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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 μL unilaterally containing ~2.42 × 1011 plasmid copy numbers (PCN) or a low-dose volume of 20 μL bilaterally (~9.67 × 1010 PCN). Rabbits were injected bilaterally with a 0.5 mL (~1.37 × 1011 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/μg 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 μL and rabbits injected with 0.5 mL, but PCN clearance was slower in mice injected with similar PCN in 50 μL (1.33 x 1013 PCN) compared to 20 μL (5.3 x 1012 PCN),. Persistence at two months in the rabbit and low-dose murine models was comparable, with geometric mean of 5.22 × 103 PCN/μg of total DNA for the low-dose volume murine model and 2.81 × 103/μg DNA for the rabbit model. Interanimal variability in persistence was not impacted by dose volume.
We now provide open access to journal articles published online for one year or more. This article may be downloaded at the following link:
Download PDF If the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.