The effect of vaccination on the response to experimental infection with bovine respiratory syncytial virus infection in calves
Bovine respiratory syncytial virus (BRSV) is an important respiratory pathogen of cattle. Both inactivated and modified live virus (MLV) BRSV vaccines are currently in use. Vaccine efficacy, the significance of qualitative differences in antibody responses, and the correlates of immunity to BRSV infection, remain unexamined by a virulent experimental challenge. This thesis addressed these issues. The functional properties of antibodies induced by a MLV and 3 inactivated BRSV vaccines were compared in feedlot calves (n = 10 per group) (trial 1). A challenge model that induces severe clinical disease and pulmonary pathology was developed by serially passing a field isolate of BRSV in newborn calves, using lung washing as the challenge inoculum. The effect of vaccination on BRSV infection was investigated. In trial 2, BRSV naive calves were vaccinated twice with a formalin inactivated (FI) vaccine, 103 pfu MLV or sham vaccinated (n = 4 per group). In trial 3, calves were vaccinated with either 2 doses of MLV intramuscularly (IM) or intradermally, with a single dose IM of MLV or MLV with an adjuvant (four groups, (n = 10 per group), or were unvaccinated (n = 10). Calves were challenged 34 days (trial 2) or 3 weeks (trial 3) after the second or only vaccination. MLV BRSV vaccines preferrentially induced antibodies with potentially protective, fusion inhibiting, properties (trial 1). Significant reductions in clinical disease, pulmonary pathology, and in trial 3, reduced virus shedding, were observed in calves vaccinated with the MLV or the FI BRSV vaccines. Decreased protection in calves that received a single dose of unadjuvanted MLV vaccine was associated with delayed post challenge serum IgG and decreased lymphoproliferative and IFNɣ responses. In trial 3, prechallenge serum antibody was not indicative of protection, but anamnestic serum and mucosal antibody responses had a low but significant negative predictive value for virus shedding and pulmonary pathology. Virus clearance in unvaccinated calves was independent of antibody and coincident with detection of BRSV specific cytotoxic cells, a response marginally accelerated by vaccination with MLV. Pulmonary emphysema and edema were independent of examined immune responses, but all vaccines were associated with an earlier clinical response to challenge.
Doctor of Philosophy (Ph.D.)