A DNA vaccine delivered by dermal electroporation fully protects cynomolgus macaques against Lassa fever.
Hum Vaccin Immunother. 2017 Oct 18;:0
Authors: Cashman KA, Wilkinson ER, Shaia CI, Facemire PR, Bell TM, Bearss JJ, Shamblin JD, Wollen SE, Broderick KE, Sardesai NY, Schmaljohn CS
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 U.S. 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 three 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 employed an accelerated vaccination strategy consisting of two administrations, spaced four 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 endpoint (45 days post-exposure). Two of the three 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.
PMID: 29045192 [PubMed - as supplied by publisher]
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