The Lamb Model

  • Lamb lung is susceptible to various strains of RSV (Long, A2 and M37 strains; Ovine and bovine strains) as well as human strains of PIV-3 and bovine PI-3 and various bacteria and other pathogens.
  • Virus delivery methods include:  Nebulization (preferred), fiberoptic bronchoscopy, nasal misters/atomizers, intratracheal.
  • Lung lesions in lambs with RSV have similar lesions to human infants:
    • replication in airways is extensive by four days post-infection–viral kinetics characterized for days up to 8 days post infection
    • bronchiolitis characterized by degeneration and necrosis of epithelial cells, syncytial cell formation, neutrophil infiltration, epithelial cell hypertrophy and hyperplasia
  • Viral parameters: Viral titers, mRNA levels (RT qPCR), viral antigen distribution and intensity (immunohistochemistry)
  • Innate and adaptive immune responses are characterized.
  • Lambs can be deprived of colostrum and thus lack anti-RSV antibodies.
  • Lamb lung size is similar to human infants affording ample tissue for sampling.
  • Preterm lambs (90% of full term) can survive and be used for studies.
  • Lambs vaccinated with formalin-inactivated RSV (FI-RSV) develop enhanced lesions.
  • Jugular veins are easily accessible for:
    • pharmacokinetics and volumes are much higher than rodents
    • drug delivery
  • Drugs can be delivered: Intravenous, aerosol/nebulizer, gastric gavage, in diet.