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

Kathleen A. Cashman²  Kate E. Broderick³  Eric R. Wilkinson²  Carl I. Shaia¹  Todd M. Bell¹  Amy C. Shurtleff⁴  Kristin W. Spik²  Catherine V. Badger²  Mary C. Guttieri²  Niranjan Y. Sardesai³ 

[1] Pathology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21702, USA; E-Mails:;Virology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21702, USA; E-Mails:;Inovio Pharmaceuticals, Inc., Blue Bell, PA 19422, USA; E-Mails:;Integrated Toxicology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21702, USA; E-Mail:

关键词: Lassa fever;    Lassa virus;    arenavirus;    guinea pigs;    dermal electroporation;    vaccination;    vaccine;   

DOI  :  10.3390/vaccines1030262

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2013 by the authors; licensee MDPI, Basel, Switzerland.