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

Alvin W. SmithCaliciTech 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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Patrick L. IversenAVI BioPharma Inc, 4575 SW Research Way, Corvallis, OR 97333.

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Peter D. O'HanleyAVI BioPharma Inc, 4575 SW Research Way, Corvallis, OR 97333.

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Douglas E. SkillingCaliciTech 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. ChristensenAVI BioPharma Inc, 4575 SW Research Way, Corvallis, OR 97333.

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

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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.

Contributor Notes

Supported by AVI BioPharma Incorporated, Oregon State University Agriculture Experimental Station, and the Oregon State University Foundation Presidents Club Fund for the Laboratory for Calicivirus Studies.

The authors thank D. Pohka and Dana White for assistance with outbreak 1 (trial 1); Johnnie Prince for assistance with outbreak 2 (trials 2 and 3); Janice Whetstone for assistance with outbreak 3 (trial 4); Chet Smith for technical assistance; and Dwight Weller, Doreen Weller, Christina Fox, and Candace Lovejoy for assistance with synthesis, purification, and quality control of the phosphorodiamidate morpholino oligomer.

Address correspondence to Dr. Smith.