Comparison of rabbit and mouse models for persistence analysis of plasmid-based vaccines.
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 microL unilaterally containing approximately 1.33 x 10(13) plasmid copy numbers (PCN) or a low-dose volume of 20 microL bilaterally ( approximately 5.3 x 10(12) PCN). Rabbits were injected bilaterally with a 0.5 mL ( approximately 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/microg 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 microL and rabbits injected with 0.5 mL, but PCN clearance was slower in mice injected with similar PCN in 50 microL (1.33 x 10(13) PCN) compared to 20 microL (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/microg of total DNA for the low-dose volume murine model and 2.81 x 10(3)/microg DNA for the rabbit model. Interanimal variability in persistence was not impacted by dose volume.
Leamy
Vicky L
VL
Vical Incorporated, San Diego, California 92121, USA.
Martin
Terrie
T
Mahajan
Rohit
R
Vilalta
Adrian
A
Rusalov
Denis
D
Hartikka
Jukka
J
Bozoukova
Vesselina
V
Hall
Keith D
KD
Morrow
Jane
J
Rolland
Alain P
AP
Kaslow
David C
DC
Lalor
Peggy A
PA
D000818:Animals; D005260:Female; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D023421:Models, Animal; D010957:Plasmids; D011817:Rabbits; D014018:Tissue Distribution; D019444:Vaccines, DNA / Q000493:pharmacokinetics*
D019444:Vaccines, DNA