Bovine T cell responses to bovine respiratory syncytial virus and a vaccine vector candidate
The literature review section of this dissertation summarizes current knowledge of BRSV, immunity to BRSV, bovine T cell biology, and methods for analyzing cell-mediated immunity (CMI) in domestic animals. Previous work indicates that CMI responses to BRSV are critical to protective immunity. Studies described here were designed to characterize BRSV-specific responses by the different T cell subsets, particularly following vaccination. In vitro assays for BRSV-specific T cell activation were performed in parallel with conventional serum virus neutralizing antibody assays. In one study, BRSV-responsive CD4+, CD8+, and gammadelta T cells were identified in calves lacking detectable antibody to the virus. It was demonstrated that these individuals had immunological memory for BRSV, as they mounted anamnestic-like antibody responses to a vaccine. The practical implications are that seronegative calves are not necessarily immunologically naive and seroconversion may not be a necessary correlate for protective immunity after vaccinating calves that have maternal antibody. In two other studies, T cell priming was monitored following immunization with commercial modified-live virus (MLV) or inactivated, adjuvanted BRSV vaccines. In the first of these experiments, calves were initially seronegative and T cell negative to BRSV. The inactivated vaccine induced higher, more sustained CD4+ and gammadelta T cell responses than MLV. Inactivated vaccine also induced CD8+ T cell responses as high as those induced by MLV. In the second of these experiments, comparable vaccines from other commercial sources were administered to calves with pre-existing antibody (presumably maternal), but no detectable T cell memory. Again, greater antigen-specific T cell responses were observed in calves receiving inactivated virus with adjuvant than those receiving MLV. These results seem to support the use of inactivated BRSV vaccines, which does not conform to usual expectations of live and inactivated vaccines. Another study examined interactions between bovine T cells and modified vaccinia virus Ankara (MVA), a potential vector for BRSV gene expression in vaccines or in vitro studies. gammadelta T cells from normal cattle tended to respond to MVA in vitro, in a manner consistent with an innate response or antigen cross-reactivity.