TC83 replicon vectored vaccine provides protection against Junin virus in guinea pigs

Vaccine. 2010 Jul 5;28(30):4713-8. doi: 10.1016/j.vaccine.2010.04.077. Epub 2010 May 7.

Abstract

Junin virus (JUNV) is the etiological agent of the potentially lethal, reemerging human disease, Argentine hemorrhagic fever (AHF). The mechanism of the disease development is not well understood and no antiviral therapy is available. Candid 1, a live-attenuated vaccine, has been developed by the US Army and is being used in the endemic area to prevent AHF. This vaccine is only approved for use in Argentina. In this study we have used the alphavirus-based approach to engineer a replicon system based on a human (United States Food and Drug Administration Investigational New Drug status) vaccine TC83 that express heterologous viral antigens, such as glycoproteins (GPC) of Junin virus (JUNV). Preclinical studies testing the immunogenicity and efficacy of TC83/GPC were performed in guinea pigs. A single dose of the live-attenuated alphavirus based vaccine expressing only GPC was immunogenic and provided partial protection, while a double dose of the same vaccine provided a complete protection against JUNV. This is the first scientific report to our knowledge that the immune response against GPC alone is sufficient to prevent lethal disease against JUNV in an animal model.

MeSH terms

  • Animals
  • Antibodies, Viral / analysis
  • Antibodies, Viral / biosynthesis
  • Arenaviridae Infections / immunology*
  • Arenaviridae Infections / prevention & control*
  • Arenaviridae Infections / virology
  • Cell Line
  • Chlorocebus aethiops
  • Cricetinae
  • DNA, Viral / genetics
  • DNA, Viral / immunology
  • Female
  • Genetic Vectors
  • Glycoproteins / chemistry
  • Glycoproteins / immunology
  • Guinea Pigs
  • Junin virus / genetics*
  • Junin virus / immunology*
  • Neutralization Tests
  • Plasmids / immunology
  • Replicon / immunology*
  • Survival Analysis
  • Telemetry
  • Vaccines, DNA / immunology
  • Vero Cells
  • Viral Load
  • Viral Plaque Assay
  • Viral Vaccines / immunology*

Substances

  • Antibodies, Viral
  • DNA, Viral
  • Glycoproteins
  • Vaccines, DNA
  • Viral Vaccines