Single-dose intranasal administration with mDEF201 (adenovirus vectored mouse interferon-alpha) confers protection from mortality in a lethal SARS-CoV BALB/c mouse model

Antiviral Res. 2011 Jan;89(1):75-82. doi: 10.1016/j.antiviral.2010.11.007. Epub 2010 Nov 18.

Abstract

Interferons (IFNs) are a first line of defense against viral infection. Herein we describe the use of an adenovirus vectored mouse IFN alpha gene (mDEF201) as a prophylactic and treatment countermeasure in a SARS-CoV-infected BALB/c mouse model. Complete survival protection was observed in mice given a single dose of mDEF201 administered intranasally 1, 3, 5, 7, or 14 days prior to lethal SARS-CoV challenge (p<0.001), and body weights of these treated mice were unaffected by the challenge. In addition, low doses of mDEF201 protected lungs in a dose dependent manner as measured by a reduction in gross pathology. Intranasal treatment with mDEF201 ranging from 10(6) to 10(8)PFU significantly protected mice against a lethal SARS-CoV infection in a dose dependent manner up to 12h post infection (p<0.001). The data suggest that mDEF201 is a new class of antiviral agent further development as treatment for SARS-CoV infections.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / genetics
  • Administration, Intranasal
  • Animals
  • Antiviral Agents / administration & dosage*
  • Antiviral Agents / immunology
  • Biological Products / administration & dosage*
  • Biological Products / genetics
  • Biological Products / immunology
  • Body Weight
  • Chlorocebus aethiops
  • Disease Models, Animal
  • Female
  • Genetic Vectors
  • Humans
  • Interferon-alpha / administration & dosage*
  • Interferon-alpha / genetics
  • Interferon-alpha / immunology
  • Mice
  • Mice, Inbred BALB C
  • SARS Virus / immunology*
  • Severe Acute Respiratory Syndrome / mortality
  • Severe Acute Respiratory Syndrome / pathology
  • Severe Acute Respiratory Syndrome / prevention & control*
  • Survival Analysis
  • Vero Cells

Substances

  • Antiviral Agents
  • Biological Products
  • Ifna protein, mouse
  • Interferon-alpha