Human Vaccines & Immunotherapeutics (Dec 2017)

A DNA vaccine delivered by dermal electroporation fully protects cynomolgus macaques against Lassa fever

  • Kathleen A. Cashman,
  • Eric R. Wilkinson,
  • Carl I. Shaia,
  • Paul R. Facemire,
  • Todd M. Bell,
  • Jeremy J. Bearss,
  • Joshua D. Shamblin,
  • Suzanne E. Wollen,
  • Kate E. Broderick,
  • Niranjan Y. Sardesai,
  • Connie S. Schmaljohn

DOI
https://doi.org/10.1080/21645515.2017.1356500
Journal volume & issue
Vol. 13, no. 12
pp. 2902 – 2911

Abstract

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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. There are no US Food and Drug Administration (FDA)-licensed vaccines available to prevent Lassa fever. 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.

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