Antiviral activity of a novel recombinant human interferon-alpha B/D hybrid.
The antiviral potential of a novel cross-species active, recombinant human interferon-alpha B/D hybrid (rHuIFN-alpha B/D), was evaluated for its efficiacy in cultured human monocytes and in several murine models of viral disease. When examined in 14-day-old human monocyte cultures, rHuIFN-alpha B/D was highly effective in preventing viral replication and cell destruction caused by herpes simplex virus type 1 (HSV-1/VR3). The effect observed with 100 units of this hybrid IFN was as good or higher than that observed with equivalent amounts of rHuIFN-alpha A or IFN-gamma. In addition, a single dose (5 X 10(7) U/kg) of rHuIFN-alpha B/D administered several hours after intranasal infection with HSV-1/VR3 suppressed pulmonary virus replication and prevented death due to interstitial pneumonia. Similarly, mice infected with a more aggressive strain of HSV-1 (McIntyre) were protected when this IFN preparation was administered at the time of virus infection and 1 day later. The anti-retroviral activity of rHuIFN-alpha B/D was examined in two murine leukemia retroviral models, Rauscher (RMLV) and Friend (FMLV), and a murine model of acquired immunodeficiency (LP-BM5). Treatment of RMLV or FMLV infected mice significantly prolonged mean survival times and the number of long-term FMLV survivors. These therapeutic effects were demonstrated when IFN was administered on the day of virus infection or as late as 3 days following infection. Transient reversal of the immunosuppressive effects induced by LP-BM5 infection was observed when rHuIFN-alpha B/D treatment was initiated at the time of virus infection. Moreover, when rHuIFN-alpha B/D was used together with azidothymidine (AZT), the effect of the combination was better than either drug alone.
Gangemi
J D
JD
Research Laboratories, Pharmaceuticals Division, CIBA-GEIGY Ltd., Basel, Switzerland.
Lazdins
J
J
Dietrich
F M
FM
Matter
A
A
Poncioni
B
B
Hochkeppel
H K
HK
D000998:Antiviral Agents; D002478:Cells, Cultured; D005622:Friend murine leukemia virus / Q000187:drug effects; D006801:Humans; D007370:Interferon Type I / Q000494:pharmacology*; D009000:Monocytes / Q000187:drug effects; D011925:Rauscher Virus / Q000187:drug effects; D011994:Recombinant Proteins; D018139:Simplexvirus / Q000187:drug effects; D013997:Time Factors; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D007370:Interferon Type I; D011994:Recombinant Proteins