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A vaccinia recombinant virus: Comparative evaluations among free-ranging, immunocompetent, and immunodeficient hosts

Posted on:1995-11-05Degree:Ph.DType:Dissertation
University:University of PennsylvaniaCandidate:Hanlon, Cathleen AlmaFull Text:PDF
GTID:1474390014990406Subject:Biology
Abstract/Summary:
An orally efficacious vaccinia-rabies glycoprotein (V-RG) recombinant virus holds promise for wildlife rabies control. Due to thymidine kinase gene inactivation, the V-RG virus is attenuated. However, it may retain parental vaccinia characteristics for accidental mucous membrane infection and other complications in immunocompromised hosts. In these studies, neonatal, prednisolone-treated, and CDV{dollar}sp1{dollar}-infected raccoons, FIV+, FeLV+, and dually-infected FeLV+, FIP+ cats, and athymic nude and SCID mice were utilized to evaluate V-RG in host models for specific vaccinia contraindications. Additionally, during the first North American V-RG field release on Parramore Island, VA, 887 free-ranging raccoons were live-trapped and examined for vaccinia-like lesions. No lesions suggestive of V-RG virus were demonstrated. The V-RG virus was recovered from tonsils of two, biomarker-positive vaccination area raccoons on days two and four following bait distribution. Survivorship was not different between baited and non-baited areas. In laboratory studies among 52 raccoons, two received 20 times the field dose per os, one dam nursing four 17 day-old kits received 10 times the field dose, eight raccoons received one vaccine-laden bait each, six were inoculated with one field dose at seven conjunctival and oral mucosal sites, 14 were less than 25 days-old upon oral, intradermal, ocular, or intranasal exposure, 21 received V-RG intradermally of which four were pretreated with prednisolone, and two had canine distemper. Notable findings in raccoons were limited to focal microscopic ulcerations at scarification sites. In 24 experimentally-infected FIV+, FeLV+, FeLV+ and FIP+, and uninfected cats, oral and intradermal inoculation of V-RG vaccine produced no clinically detectable adverse effects. In athymic nude mice, multi-systemic infection followed severe intradermal V-RG inoculation, but with a decrease in positive tissues and viral titers over time. In SCID mice, V-RG was innocuous by the oral route. Parenteral V-RG inoculation produced progressive lesions but at a significantly slower rate than with vaccinia. Administration of vaccinia immune globulin and hydroxyphosphonylmethoxypropylcytosine (HPMPC) resulted in regression of V-RG infection in SCID mice. ftn{dollar}sp1{dollar}CDV-Canine distemper virus. FIV-Feline immunodeficiency virus. FeLV-Feline leukemia virus. FIP-Feline infectious peritonitis. SCID-Severe combined immunodeficiency.
Keywords/Search Tags:V-RG, Virus, Vaccinia, SCID mice, Felv, Oral
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