Understanding trypanosome-mediated immunosuppression of B cell memory responses in cattle.

Existing infections, coinfections, and health interventions interact in a complex way to impact upon disease severity and animal health. However, there are few tractable experimental systems available to study how these interactions affect vaccination outcome. This project leverages a combination of experimental platforms, immunological tools and recent advances in capabilities, to address how the immunosuppression induced by trypanosome infection in cattle impacts vaccine efficacy, using foot-and-mouth disease virus (FMDV) as a well characterised model vaccine that acts via the B-cell and antibody responses. Trypanosome infections pose a major challenge to livestock health across sub-Saharan Africa, South America and Asia, where they are co-endemic with other significant diseases such as FMD for which vaccination is a key element of control.  Trypanosomes suppress the immune system, a process well-documented in mice, leading to the disruption and loss of B-cell populations and severe impairment of immune memory and B-cell/antibody recall responses – including to non-trypanosome immunisations. In mouse models, this phenotype is mediated by natural killer (NK-) cells through a perforin-dependent mechanism that kills B-cells. However, while field observations and preliminary data suggest that similar immunosuppression occurs in the clinically relevant bovine host, this important and relevant phenotype has not yet been characterised in cattle.
This project will investigate to which extent Trypanosoma brucei infection may undermine vaccine-induced immunity in cattle. Key objectives are:
- Examine the effect of T. brucei infection upon B- and NK-cell populations in cattle, identifying key  affected subsets and correlates of immunosuppression.
- Assess the effect of T. brucei infection timing and clearance on vaccine recall responses, using FMDV as a model vaccine antigen.
To achieve these objectives, we will employ advanced methods, including spectral flow...