title: 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.
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.
authors.affiliation: Hemispherx Biopharma, Inc., Philadelphia, PA 19103, United States.
authors.forename: David R
authors.initials: DR
authors.lastname: Strayer
authors.affiliation: Hemispherx Biopharma, Inc., Philadelphia, PA 19103, United States.
authors.forename: William A
authors.initials: WA
authors.lastname: Carter
authors.affiliation: B.C.S. Consulting, Newtown Square, PA 19073, United States.
authors.forename: Bruce C
authors.initials: BC
authors.lastname: Stouch
authors.affiliation: Viroclinics Biosciences BV, 3029 AK Rotterdam, The Netherlands.
authors.forename: Koert J
authors.initials: KJ
authors.lastname: Stittelaar
authors.affiliation: Global Pathology Support, 2596 BA The Hague, The Netherlands.
authors.forename: Robert J M M
authors.initials: RJ
authors.lastname: Thoolen
authors.affiliation: Viroclinics Biosciences BV, 3029 AK Rotterdam, The Netherlands.
authors.forename: Albert D M E
authors.initials: AD
authors.lastname: Osterhaus
authors.affiliation: Vanderbilt University, Nashville, TN 37232, United States.
authors.forename: William M
authors.initials: WM
authors.lastname: Mitchell
mesh_terms: D000284:Administration, Oral; D000818:Animals; D004195:Disease Models, Animal; D006470:Hemorrhage / Q000517:prevention & control; D006801:Humans; D007249:Inflammation / Q000517:prevention & control; D053124:Influenza A Virus, H5N1 Subtype / Q000472:pathogenicity; D016898:Interferon-alpha / Q000008:administration & dosage / Q000494:pharmacology*; D055370:Lung Injury / Q000517:prevention & control*; D008252:Macaca fascicularis / Q000821:virology; D008992:Monkey Diseases / Q000188:drug therapy* / Q000821:virology; D009061:Mouth Mucosa; D009976:Orthomyxoviridae Infections / Q000188:drug therapy* / Q000517:prevention & control; D011650:Pulmonary Alveoli / Q000473:pathology / Q000821:virology; D014779:Virus Replication / Q000187:drug effects
chemical_list: D016898:Interferon-alpha
keywords: H5N1; Highly pathogenic; Influenza virus; Interferon; Oro-mucosal (buccal) administration
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