Construction and nonclinical testing of a Puumala virus synthetic M gene-based DNA vaccine

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Abstract

Puumala virus (PUUV) is a causative agent of hemorrhagic fever with renal syndrome (HFRS). Although PUUV-associated HFRS does not result in high case-fatality rates, the social and economic impact is considerable. There is no licensed vaccine or specific therapeutic to prevent or treat HFRS. Here we report the synthesis of a codon-optimized, full-lengthMsegment open reading frame and its cloning into a DNA vaccine vector to produce the plasmid pWRG/PUU-M(s2). pWRG/PUU-M(s2) delivered by gene gun produced high-titer neutralizing antibodies in hamsters and nonhuman primates. Vaccination with pWRG/ PUU-M(s2) protected hamsters against infection with PUUV but not against infection by related HFRS-associated hantaviruses. Unexpectedly, vaccination protected hamsters in a lethal disease model of Andes virus (ANDV) in the absence of ANDV crossneutralizing antibodies. This is the first evidence that an experimental DNA vaccine for HFRS can provide protection in a hantavirus lethal disease model. Copyright © 2013, American Society for Microbiology. All Rights Reserved.

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Brocato, R. L., Josleyn, M. J., Wahl-Jensen, V., Schmaljohn, C. S., & Hooper, J. W. (2013). Construction and nonclinical testing of a Puumala virus synthetic M gene-based DNA vaccine. Clinical and Vaccine Immunology, 20(2), 218–226. https://doi.org/10.1128/CVI.00546-12

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