Enhanced Efficacy of a Codon-Optimized DNA Vaccine Encoding the Glycoprotein Precursor Gene of Lassa Virus in a Guinea Pig Disease Model When Delivered by Dermal Electroporation
Abstract
:1. Introduction
2. Experimental Section
2.1. Construction of the Non-Optimized Lassa Josiah GPC Vaccine Plasmid
2.2. Construction of Codon-Optimized Lassa Josiah GPC Vaccine Plasmid
2.3. Immunoprecipitation
2.4. Electroporation Devices
2.4.1. Intramuscular Electroporation Device (IMEP)
2.4.2. ELGEN-Minimally Invasive Dermal Electroporation Device (ELGEN-MID)
2.5. Pilot Study: IMEP with a Non-Optimized DNA Construct
2.6. Follow-On Study: IMEP versus ELGEN-MID with a Codon-Optimized Construct
2.7. Backchallenge of Codon-Optimized LASV-GPC Vaccine Survivors
2.8. Analysis of Viremia and Neutralizing Antibody Titers
2.9. Immunohistochemisty
3. Results and Discussion
3.1. GPC Expression from the pLASV-GPC Plasmid
3.2. A Non-Optimized Lassa Virus DNA Vaccine Prevents Death but not Illness in Guinea Pigs When Administered by IMEP
Treatment Group | Day 0 Postinfection | Day 30 Postinfection | ||
---|---|---|---|---|
PRNT50 | PRNT80 | PRNT50 | PRNT80 | |
Mock Vaccine | None | None | - | - |
IMEP | None | None | 256 | 16 |
3.3. Codon Optimization of the DNA Vaccine Enhances Its Ability to Prevent Viremia and Illness as well as Death in Guinea Pigs
Treatment Group | Day 0 Postinfection | Day 30 Postinfection | ||
---|---|---|---|---|
PRNT50 | PRNT80 | PRNT50 | PRNT80 | |
Mock IMEP | None | None | - | - |
Mock ELGEN-MID | None | None | - | - |
IMEP | >8 b | None | 32 | 8 |
ELGEN-MID | 8 | None | 32 | 8 |
3.4. Surviving ELGEN-MID-Vaccinated Animals Are Free from Disease Pathology Compared to Mock-Vaccinated Controls
3.5. ELGEN-MID-Vaccinated Animals Survive Secondary Exposure to a Lethal Dose of LASV
4. Conclusions
Acknowledgments
Conflict of Interest
References
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Cashman, K.A.; Broderick, K.E.; Wilkinson, E.R.; Shaia, C.I.; Bell, T.M.; Shurtleff, A.C.; Spik, K.W.; Badger, C.V.; Guttieri, M.C.; Sardesai, N.Y.; et al. Enhanced Efficacy of a Codon-Optimized DNA Vaccine Encoding the Glycoprotein Precursor Gene of Lassa Virus in a Guinea Pig Disease Model When Delivered by Dermal Electroporation. Vaccines 2013, 1, 262-277. https://doi.org/10.3390/vaccines1030262
Cashman KA, Broderick KE, Wilkinson ER, Shaia CI, Bell TM, Shurtleff AC, Spik KW, Badger CV, Guttieri MC, Sardesai NY, et al. Enhanced Efficacy of a Codon-Optimized DNA Vaccine Encoding the Glycoprotein Precursor Gene of Lassa Virus in a Guinea Pig Disease Model When Delivered by Dermal Electroporation. Vaccines. 2013; 1(3):262-277. https://doi.org/10.3390/vaccines1030262
Chicago/Turabian StyleCashman, Kathleen A., Kate E. Broderick, Eric R. Wilkinson, Carl I. Shaia, Todd M. Bell, Amy C. Shurtleff, Kristin W. Spik, Catherine V. Badger, Mary C. Guttieri, Niranjan Y. Sardesai, and et al. 2013. "Enhanced Efficacy of a Codon-Optimized DNA Vaccine Encoding the Glycoprotein Precursor Gene of Lassa Virus in a Guinea Pig Disease Model When Delivered by Dermal Electroporation" Vaccines 1, no. 3: 262-277. https://doi.org/10.3390/vaccines1030262