Recipient Organization
IOWA STATE UNIVERSITY
2229 Lincoln Way
AMES,IA 50011
Performing Department
Veterinary Medicine
Non Technical Summary
There are advantages and disadvantages of the ovine model of RSV in contrast to other models. Overall, in our view, the ovine model has more advantages than disadvantages and better mimicks the human condition than certain other models. New therapeutic compounds to prevent or treat RSV are needed. Work in this proposal further develops the ovine model in its use in testing new anti-RSV compounds. Work Aim 1 work determines the extent to which a viral strain with considerable virulence to humans (RSV-A Memphis 37 strain) (M37) causes disease in lambs when aerosolized or delivered intranasally. Aim 2 determines the extent to which new drugs prevent M37 infection and disease.
Animal Health Component
(N/A)
Research Effort Categories
Basic
(N/A)
Applied
(N/A)
Developmental
(N/A)
Goals / Objectives
I am unaware that this proposal was approved by NIFA. It is grant funded by a private company, Gilead, Inc. Aim 1.1. Determines the susceptibility of lambs to respiratory syncytial virus (RSV) strain Memphis 37 (M37) delivered by aerosolization or intranasal inoculation with an atomizer. Aim 1.2. Determines the kinetics of M37 disease severity in lambs. Aim 2.1. Determines the efficacy of newly formulated drugs when administered prophylactically in inhibiting M37 disease.
Project Methods
Aim 1.1. M37 strain will be inoculated into lambs with an nebulizer or atomizer and clinical signs, temperature, respiratory rates and nasal swabs will be collected. At six days post-inoculation (peak infection) lambs are necropsied and lung is assessed for disease severity (lesions), RSV titers, RSV mRNA levels, RSV antigen, and inflammatory mediators. Aim 1.2. Lambs are inoculated with M37 by the method above (nebulizer or atomizer) that causes consistent disease and clinical signs, temperature and respiratory rates will be monitored. Groups of lambs will be necropsied at set timepoints post-inoculation (day, 1, 2, 3, 4, 5, 7, 9 and 14) and viral outputs (above), lesions, and inflammatory mediators will be measured. Controls lack M37 inoculation and will be assessed the same. Aim 2. Lambs will be pre-treated by intravenous delivery of a new anti-RSV drug and then inoculated with M37; controls will lack the drug but receive M37. Disease severity will be measure as above.