Priming of multiple T cell subsets by modified-live and inactivated bovine respiratory syncytial virus vaccines

Abstract

T cell activity is a critical component of immunity to bovine respiratory syncytial virus (BRSV). We tested the effects of immunization by modified-live and inactivated BRSV vaccines on cell-mediated and humoral immunity in young calves. The two forms of vaccine stimulated similar serum neutralizing antibody production, although the early kinetics of those responses differed. CD4 +, CD8 +, and γδ T cells were analyzed before and after immunization for BRSV-specific in vitro recall responses, as evaluated by CD25 upregulation measured by flow cytometry. Modified-live virus (MLV) primed each of the three subsets for statistically significant in vitro responses to antigen. Inactivated vaccine also primed each T cell population for significant antigen-driven CD25 upregulation, including responses by CD4 + and γδ T cells that were stronger and longer-lasting than those primed by MLV. Monoclonal antibody was used in additional assays to block MHC class I during incubation of BRSV antigen with peripheral blood mononuclear cells from an animal in the inactivated vaccine group. The recall response by CD8 + T cells was more inhibited by this treatment than the other subsets, further suggesting that the inactivated vaccine had primed antigen-specific CD8 + T cells. In summary, the data indicate that balanced BRSV-specific T cell responses can be induced by inactivated, as well as modified-live, conventional vaccines, which may implicate an alternative pathway of MHC class I antigen presentation.