Limits...
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.

Cashman KA, Broderick KE, Wilkinson ER, Shaia CI, Bell TM, Shurtleff AC, Spik KW, Badger CV, Guttieri MC, Sardesai NY, Schmaljohn CS - Vaccines (Basel) (2013)

Bottom Line: Vaccinated GPs were protected from lethal infection (5/6) with LASV compared to the controls.Together, these innovations resulted in enhanced efficacy of the vaccine.The vaccinated GPs were never ill and were not viremic at any timepoint.

View Article: PubMed Central - PubMed

Affiliation: Virology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21702, USA. kathleen.cashman@us.army.mil.

ABSTRACT
Lassa virus (LASV) causes a severe, often fatal, hemorrhagic fever endemic to West Africa. Presently, there are no FDA-licensed medical countermeasures for this disease. In a pilot study, we constructed a DNA vaccine (pLASV-GPC) that expressed the LASV glycoprotein precursor gene (GPC). This plasmid was used to vaccinate guinea pigs (GPs) using intramuscular electroporation as the delivery platform. Vaccinated GPs were protected from lethal infection (5/6) with LASV compared to the controls. However, vaccinated GPs experienced transient viremia after challenge, although lower than the mock-vaccinated controls. In a follow-on study, we developed a new device that allowed for both the vaccine and electroporation pulse to be delivered to the dermis. We also codon-optimized the GPC sequence of the vaccine to enhance expression in GPs. Together, these innovations resulted in enhanced efficacy of the vaccine. Unlike the pilot study where neutralizing titers were not detected until after virus challenge, modest neutralizing titers were detected in guinea pigs before challenge, with escalating titers detected after challenge. The vaccinated GPs were never ill and were not viremic at any timepoint. The combination of the codon-optimized vaccine and dermal electroporation delivery is a worthy candidate for further development.

No MeSH data available.


Related in: MedlinePlus

Outcomes for IMEP study using the non-optimized LASV DNA construct. (A) Survival curve; (B) Serum viremia as measured by plaque assay; (C) Morbidity score based on observed disease signs.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4494234&req=5

vaccines-01-00262-f002: Outcomes for IMEP study using the non-optimized LASV DNA construct. (A) Survival curve; (B) Serum viremia as measured by plaque assay; (C) Morbidity score based on observed disease signs.

Mentions: For the pilot study, we produced a candidate LASV DNA vaccine by cloning cDNA encoding the GPC gene of LASV (Josiah strain) into the plasmid vector pWRG7077 [21]. Approximately 4 weeks after the final vaccinations, the guinea pigs were challenged by SC administration of 1,000 pfu of LASV, a standard lethal challenge dose. All of the mock-vaccinated guinea pigs succumbed to LASV infection whereas all but one of the IMEP-vaccinated guinea pigs survived. The IMEP-vaccinated animal that died showed a delayed time to death as compared to controls (Figure 2A). Although the DNA vaccine prevented death in most animals, the challenged guinea pigs developed transient viremia (Figure 2B) and showed mild clinical signs of disease (Figure 2C).


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.

Cashman KA, Broderick KE, Wilkinson ER, Shaia CI, Bell TM, Shurtleff AC, Spik KW, Badger CV, Guttieri MC, Sardesai NY, Schmaljohn CS - Vaccines (Basel) (2013)

Outcomes for IMEP study using the non-optimized LASV DNA construct. (A) Survival curve; (B) Serum viremia as measured by plaque assay; (C) Morbidity score based on observed disease signs.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4494234&req=5

vaccines-01-00262-f002: Outcomes for IMEP study using the non-optimized LASV DNA construct. (A) Survival curve; (B) Serum viremia as measured by plaque assay; (C) Morbidity score based on observed disease signs.
Mentions: For the pilot study, we produced a candidate LASV DNA vaccine by cloning cDNA encoding the GPC gene of LASV (Josiah strain) into the plasmid vector pWRG7077 [21]. Approximately 4 weeks after the final vaccinations, the guinea pigs were challenged by SC administration of 1,000 pfu of LASV, a standard lethal challenge dose. All of the mock-vaccinated guinea pigs succumbed to LASV infection whereas all but one of the IMEP-vaccinated guinea pigs survived. The IMEP-vaccinated animal that died showed a delayed time to death as compared to controls (Figure 2A). Although the DNA vaccine prevented death in most animals, the challenged guinea pigs developed transient viremia (Figure 2B) and showed mild clinical signs of disease (Figure 2C).

Bottom Line: Vaccinated GPs were protected from lethal infection (5/6) with LASV compared to the controls.Together, these innovations resulted in enhanced efficacy of the vaccine.The vaccinated GPs were never ill and were not viremic at any timepoint.

View Article: PubMed Central - PubMed

Affiliation: Virology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21702, USA. kathleen.cashman@us.army.mil.

ABSTRACT
Lassa virus (LASV) causes a severe, often fatal, hemorrhagic fever endemic to West Africa. Presently, there are no FDA-licensed medical countermeasures for this disease. In a pilot study, we constructed a DNA vaccine (pLASV-GPC) that expressed the LASV glycoprotein precursor gene (GPC). This plasmid was used to vaccinate guinea pigs (GPs) using intramuscular electroporation as the delivery platform. Vaccinated GPs were protected from lethal infection (5/6) with LASV compared to the controls. However, vaccinated GPs experienced transient viremia after challenge, although lower than the mock-vaccinated controls. In a follow-on study, we developed a new device that allowed for both the vaccine and electroporation pulse to be delivered to the dermis. We also codon-optimized the GPC sequence of the vaccine to enhance expression in GPs. Together, these innovations resulted in enhanced efficacy of the vaccine. Unlike the pilot study where neutralizing titers were not detected until after virus challenge, modest neutralizing titers were detected in guinea pigs before challenge, with escalating titers detected after challenge. The vaccinated GPs were never ill and were not viremic at any timepoint. The combination of the codon-optimized vaccine and dermal electroporation delivery is a worthy candidate for further development.

No MeSH data available.


Related in: MedlinePlus