Protection from pulmonary tissue damage associated with infection of cynomolgus macaques by highly pathogenic avian influenza virus (H5N1) by low dose natural human IFN-α administered to the buccal mucosa

Antiviral Res. 2014 Oct:110:175-80. doi: 10.1016/j.antiviral.2014.07.010. Epub 2014 Aug 9.

Abstract

Using an established nonhuman primate model for H5N1 highly pathogenic influenza virus infection in humans, we have been able to demonstrate the prophylactic mitigation of the pulmonary damage characteristic of human fatal cases from primary influenza virus pneumonia with a low dose oral formulation of a commercially available parenteral natural human interferon alpha (Alferon N Injection®). At the highest oral dose (62.5IU/kg body weight) used there was a marked reduction in the alveolar inflammatory response with minor evidence of alveolar and interstitial edema in contrast to the hemorrhage and inflammatory response observed in the alveoli of control animals. The mitigation of severe damage to the lower pulmonary airway was observed without a parallel reduction in viral titers. Clinical trial data will be necessary to establish its prophylactic human efficacy for highly pathogenic influenza viruses.

Keywords: H5N1; Highly pathogenic; Influenza virus; Interferon; Oro-mucosal (buccal) administration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Animals
  • Disease Models, Animal
  • Hemorrhage / prevention & control
  • Humans
  • Inflammation / prevention & control
  • Influenza A Virus, H5N1 Subtype / pathogenicity
  • Interferon-alpha / administration & dosage
  • Interferon-alpha / pharmacology*
  • Lung Injury / prevention & control*
  • Macaca fascicularis / virology
  • Monkey Diseases / drug therapy*
  • Monkey Diseases / virology
  • Mouth Mucosa
  • Orthomyxoviridae Infections / drug therapy*
  • Orthomyxoviridae Infections / prevention & control
  • Pulmonary Alveoli / pathology
  • Pulmonary Alveoli / virology
  • Virus Replication / drug effects

Substances

  • Interferon-alpha