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

•Highly pathogenic avian influenza viruses cause extensive pulmonary damage.•A low dose oral formulation of natural human interferon-α (Alferon LDO) inhibits H5N1 induced pulmonary damage.•All fatal human cases of H5N1 exhibit Acute Respiratory Disease Syndrome (ARDS).•Emerging highly pathogenic avian influenza viruses (H5N1, H7N9, and others) are a major pandemic threat.•Similar results have been observed with type-1 IFN amelioration of pulmonary damage with SARS-CoV.

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 (62.5 IU/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.