Prevention of lethal respiratory vaccinia infections in mice with interferon-alpha and interferon-gamma.
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.
Liu
Ge
G
Advanced Biosystems, Inc, 10900 University Blvd MSN 1A8, Manassas, VA 20110, USA. ge.liu@analex.com
Zhai
Qingzhu
Q
Schaffner
Dustin J
DJ
Wu
Aiguo
A
Yohannes
Adiamseged
A
Robinson
Tanisha M
TM
Maland
Matt
M
Wells
Jay
J
Voss
Thomas G
TG
Bailey
Charlie
C
Alibek
Ken
K
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
D000998:Antiviral Agents; D016898:Interferon-alpha; D007371:Interferon-gamma