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

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.

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Document Details

Document Type
Technical Report
Publication Date
Dec 12, 2012
Accession Number
ADA582839

Entities

People

  • C. S. Schmaljohn
  • J. W. Hooper
  • M. J. Josleyn
  • R. L. Brocato
  • V. Wahl-jensen

Organizations

  • United States Army Medical Research Institute of Infectious Diseases

Tags

Communities of Interest

  • Biomedical

DTIC Thesaurus Topics

  • Amino Acids
  • Anti-Bacterial Agents
  • Antibodies
  • Biological Products
  • Bunyaviridae Infections
  • Chemical Synthesis
  • Chemistry
  • Construction
  • Epidermis
  • Gene Expression
  • Genetic Code
  • Immunogenicity
  • Infection
  • Infectious Diseases
  • Statistical Analysis
  • Vaccines
  • Viruses

Fields of Study

  • Biology

Readers

  • Molecular Genetics
  • Virology (or Medical Virology).

Technology Areas

  • Biotechnology