A DNA vaccine delivered by dermal electroporation fully protects cynomolgus macaques against Lassa fever. Issue 12 (2nd December 2017)

• Record Type: Journal Article
• Authors: Cashman, Kathleen A.; Wilkinson, Eric R.; Shaia, Carl I.; Facemire, Paul R.; Bell, Todd M.; Bearss, Jeremy J.; Shamblin, Joshua D.; Wollen, Suzanne E.; Broderick, Kate E.; Sardesai, Niranjan Y.; Schmaljohn, Connie S.
• Is Part Of: Human vaccines & immunotherapeutics. Volume 13:Issue 12(2017)
• Page Start: 2902
• Page End: 2911
• Publication Date: 2017-12-02
• Subjects: Lassa fever -- DNA vaccine -- electroporation; Vaccines -- Periodicals; 615.372
• DOI: 10.1080/21645515.2017.1356500
• Languages: English
• ISSNs: 2164-5515

Abstract

ABSTRACT: Lassa virus (LASV) is an ambisense RNA virus in the Arenaviridae family and is the etiological agent of Lassa fever, a severe hemorrhagic disease endemic to West and Central Africa. 1, 2 There are no US Food and Drug Administration (FDA)-licensed vaccines available to prevent Lassa fever. 1, 2 in our previous studies, we developed a gene-optimized DNA vaccine that encodes the glycoprotein precursor gene of LASV (Josiah strain) and demonstrated that 3 vaccinations accompanied by dermal electroporation protected guinea pigs from LASV-associated illness and death. Here, we describe an initial efficacy experiment in cynomolgus macaque nonhuman primates (NHPs) in which we followed an identical 3-dose vaccine schedule that was successful in guinea pigs, and a follow-on experiment in which we used an accelerated vaccination strategy consisting of 2 administrations, spaced 4 weeks apart. In both studies, all of the LASV DNA-vaccinated NHPs survived challenge and none of them had measureable, sustained viremia or displayed weight loss or other disease signs post-exposure. Three of 10 mock-vaccinates survived exposure to LASV, but all of them became acutely ill post-exposure and remained chronically ill to the study end point (45 d post-exposure). Two of the 3 survivors experienced sensorineural hearing loss (described elsewhere). These results clearly demonstrate that the LASV DNA vaccine combined with dermal electroporation is a highly effective candidate for eventual use in humans.