Virus-specific antiviral treatment for controlling severe and fatal outbreaks of feline calicivirus infection

Alvin W. Smith CaliciTech International, 26833 Sulphur Springs Rd, Corvallis, OR 97330.
Laboratory for Calicivirus Studies, College of Veterinary Medicine, Oregon State University, Corvallis, OR 97331.

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 DVM, PhD
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Patrick L. Iversen AVI BioPharma Inc, 4575 SW Research Way, Corvallis, OR 97333.

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 PhD
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Peter D. O'Hanley AVI BioPharma Inc, 4575 SW Research Way, Corvallis, OR 97333.

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 MD, PhD, MPH
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Douglas E. Skilling CaliciTech International, 26833 Sulphur Springs Rd, Corvallis, OR 97330.
Laboratory for Calicivirus Studies, College of Veterinary Medicine, Oregon State University, Corvallis, OR 97331.

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Janet R. Christensen AVI BioPharma Inc, 4575 SW Research Way, Corvallis, OR 97333.

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Sherry S. Weaver Animal Hospital of Towne Lake, 2990 Eagle Dr, Woodstock, GA 30189.

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Kimberli Longley Greenhill Humane Society, 88530 Greenhill Rd, Eugene, OR 97402.

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Michael A. Stone Animal Critical Care and Emergency Services, 11536 Lake City Way NE, Seattle, WA 98125.

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Steve E. Poet Best Friends Animal Hospital of East Medford, 980 N Phoenix Rd, Medford, OR 97504.

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David O. Matson Graduate Program in Public Health, East Virginia Medical School and Old Dominion University, 700 W Olney Rd, Norfolk, VA 23501-1980.

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 MD, PhD

Abstract

Objective—To test the life-sparing and therapeutic effect of a parenterally administered virus-specific antiviral phosphorodiamidate morpholino oligomer (PMO) for treating kittens during outbreaks of severe viral disease.

Animals—112 kittens of various sex and age in 4 trials involving 3 outbreaks of naturally developing caliciviral disease.

Procedures—Each trial provided an opportunity to investigate the disease. A calicivirus isolated from the liver of a cat that died with hemorrhage and hepatitis was sequenced, and a PMO that had sequence specificity complementary to a 5' region was synthesized. In vitro efficacy of the PMO was tested against the isolate, followed by 3 trials in outbreaks of severe caliciviral disease. The PMO was administered starting on day 1 of disease onset (0.7 to 5.0 mg/kg, SC, q 24 h) and continuing for up to 7 days. Survival time, clinical recovery, and caliciviral shedding were compared by use of various antiviral dosages. In a fourth trial involving nonfatal disease, a control treatment was administered for comparison.

Results—In vitro blockage of caliciviral replication by the PMO was dose dependent. In trials 1 to 3 in which survival was the endpoint, 47 of 59 cats receiving PMO survived but only 3 of 31 survived without PMO treatment. Antiviral treatment reduced viral shedding and hastened clinical recovery, as measured by weight gains and clinical condition.

Conclusions and Clinical Relevance—These data provided evidence that virus-specific PMOs were effective in treating kittens with severe Vesivirus disease and suggested a broader application for other viruses and species, including humans.

Abstract

Objective—To test the life-sparing and therapeutic effect of a parenterally administered virus-specific antiviral phosphorodiamidate morpholino oligomer (PMO) for treating kittens during outbreaks of severe viral disease.

Animals—112 kittens of various sex and age in 4 trials involving 3 outbreaks of naturally developing caliciviral disease.

Procedures—Each trial provided an opportunity to investigate the disease. A calicivirus isolated from the liver of a cat that died with hemorrhage and hepatitis was sequenced, and a PMO that had sequence specificity complementary to a 5' region was synthesized. In vitro efficacy of the PMO was tested against the isolate, followed by 3 trials in outbreaks of severe caliciviral disease. The PMO was administered starting on day 1 of disease onset (0.7 to 5.0 mg/kg, SC, q 24 h) and continuing for up to 7 days. Survival time, clinical recovery, and caliciviral shedding were compared by use of various antiviral dosages. In a fourth trial involving nonfatal disease, a control treatment was administered for comparison.

Results—In vitro blockage of caliciviral replication by the PMO was dose dependent. In trials 1 to 3 in which survival was the endpoint, 47 of 59 cats receiving PMO survived but only 3 of 31 survived without PMO treatment. Antiviral treatment reduced viral shedding and hastened clinical recovery, as measured by weight gains and clinical condition.

Conclusions and Clinical Relevance—These data provided evidence that virus-specific PMOs were effective in treating kittens with severe Vesivirus disease and suggested a broader application for other viruses and species, including humans.

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