title: Prevention of lethal respiratory vaccinia infections in mice with interferon-alpha and interferon-gamma.
abstract: The antiviral efficacy of interferons (IFNs) was evaluated using a vaccinia intranasal infection model in mice in this study. We provide evidence that intranasal administration of IFN-alpha and IFN-gamma (days -1 to +3) resulted in 100 and 90% survival against a lethal respiratory vaccinia infection (8 LD50) in mice, respectively; whereas no animals in the placebo group survived through the study period (21 days). The IFN treatment consisted of a single daily dose of 5x10(3) U per mouse for 5 consecutive days. The efficacy of IFN-gamma was evident even when the IFN-gamma treatments started 1-2 days after infection and when a lower dose (2x10(3) U per mouse) was used. The treatment of IFN-alpha and IFN-gamma reduced the virus titers in the lungs of infected mice by 1000-10,000-fold, when the administration started 1 day after infection. Our data suggest that IFN-alpha and IFN-gamma are effective in protecting vaccinia-infected mice from viral replication in lungs and mortality, and may be beneficial in other human orthopoxvirus infections.
authors.affiliation: Advanced Biosystems, Inc, 10900 University Blvd MSN 1A8, Manassas, VA 20110, USA. ge.liu@analex.com
authors.forename: Ge
authors.initials: G
authors.lastname: Liu
authors.forename: Qingzhu
authors.initials: Q
authors.lastname: Zhai
authors.forename: Dustin J
authors.initials: DJ
authors.lastname: Schaffner
authors.forename: Aiguo
authors.initials: A
authors.lastname: Wu
authors.forename: Adiamseged
authors.initials: A
authors.lastname: Yohannes
authors.forename: Tanisha M
authors.initials: TM
authors.lastname: Robinson
authors.forename: Matt
authors.initials: M
authors.lastname: Maland
authors.forename: Jay
authors.initials: J
authors.lastname: Wells
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Voss
authors.forename: Charlie
authors.initials: C
authors.lastname: Bailey
authors.forename: Ken
authors.initials: K
authors.lastname: Alibek
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D001835:Body Weight; D016898:Interferon-alpha / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D007371:Interferon-gamma / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D051379:Mice; D012141:Respiratory Tract Infections / Q000401:mortality / Q000517:prevention & control*; D016019:Survival Analysis; D014615:Vaccinia / Q000188:drug therapy* / Q000401:mortality / Q000821:virology; D014616:Vaccinia virus / Q000187:drug effects / Q000254:growth & development; D010948:Viral Plaque Assay; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D007371:Interferon-gamma