Comparison of Rabbit and Mouse Models for Persistence Analysis of Plasmid-Based Vaccines
| Autor: | Jukka Hartikka, Terrie Martin, David C. Kaslow, Alain Rolland, Denis Rusalov, Keith Hall, Jane Morrow, Vicky Leamy, Peggy Lalor, Adrian Vilalta, Rohit Mahajan, Vesselina Bozoukova |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Male
Muscle tissue Mice Inbred ICR Biodistribution Chemistry Immunology Virology Molecular biology Persistence (computer science) Mice Real-time polymerase chain reaction Plasmid medicine.anatomical_structure Murine model Models Animal Injection site Vaccines DNA Rabbit model medicine Animals Female Tissue Distribution Rabbits General Pharmacology Toxicology and Pharmaceutics Plasmids |
| Zdroj: | Human Vaccines. 2:113-118 |
| ISSN: | 1554-8619 1554-8600 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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