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Vaccines

Construction and Nonclinical Testing of a Puumala Virus Synthetic M Gene-Based DNA Vaccine

R. L. Brocato, M. J. Josleyn, V. Wahl-Jensen, C. S. Schmaljohn, J. W. Hooper
R. L. Brocato
aVirology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland, USA
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M. J. Josleyn
aVirology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland, USA
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V. Wahl-Jensen
aVirology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland, USA
bIntegrated Research Facility at Fort Detrick, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, Frederick, MD, USA
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C. S. Schmaljohn
cScience and Technology, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland, USA
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J. W. Hooper
aVirology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland, USA
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DOI: 10.1128/CVI.00546-12
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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-length M segment 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 cross-neutralizing antibodies. This is the first evidence that an experimental DNA vaccine for HFRS can provide protection in a hantavirus lethal disease model.

FOOTNOTES

    • Received 18 September 2012.
    • Returned for modification 24 October 2012.
    • Accepted 2 December 2012.
    • Accepted manuscript posted online 12 December 2012.
  • Supplemental material for this article may be found at http://dx.doi.org/10.1128/CVI.00546-12.

  • Copyright © 2013, American Society for Microbiology. All Rights Reserved.
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Construction and Nonclinical Testing of a Puumala Virus Synthetic M Gene-Based DNA Vaccine
R. L. Brocato, M. J. Josleyn, V. Wahl-Jensen, C. S. Schmaljohn, J. W. Hooper
Clinical and Vaccine Immunology Jan 2013, 20 (2) 218-226; DOI: 10.1128/CVI.00546-12

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Construction and Nonclinical Testing of a Puumala Virus Synthetic M Gene-Based DNA Vaccine
R. L. Brocato, M. J. Josleyn, V. Wahl-Jensen, C. S. Schmaljohn, J. W. Hooper
Clinical and Vaccine Immunology Jan 2013, 20 (2) 218-226; DOI: 10.1128/CVI.00546-12
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