Vaccines 2013, 1(3), 262-277; doi:10.3390/vaccines1030262
Article

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

1 Virology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21702, USA 2 Inovio Pharmaceuticals, Inc., Blue Bell, PA 19422, USA 3 Pathology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21702, USA 4 Integrated Toxicology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21702, USA 5 Office of the Chief Scientists, Headquarters, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21702, USA Present address: Metabiota, 1410 Q Street NW, Suite 300, Washington, DC 20009, USA
* Author to whom correspondence should be addressed.
Received: 31 May 2013; in revised form: 8 July 2013 / Accepted: 10 July 2013 / Published: 18 July 2013
(This article belongs to the Special Issue DNA Vaccines)
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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.
Keywords: Lassa fever; Lassa virus; arenavirus; guinea pigs; dermal electroporation; vaccination; vaccine

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MDPI and ACS Style

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.; Schmaljohn, C.S. 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.

AMA Style

Cashman KA, Broderick KE, Wilkinson ER, Shaia CI, Bell TM, Shurtleff AC, Spik KW, Badger CV, Guttieri MC, Sardesai NY, Schmaljohn CS. 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.

Chicago/Turabian Style

Cashman, Kathleen A.; Broderick, Kate E.; Wilkinson, Eric R.; Shaia, Carl I.; Bell, Todd M.; Shurtleff, Amy C.; Spik, Kristin W.; Badger, Catherine V.; Guttieri, Mary C.; Sardesai, Niranjan Y.; Schmaljohn, Connie S. 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.

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