Trypanosome parasites suppress the immune systems of infected cattle, and this project will measure exactly how badly that undermines vaccination against foot-and-mouth disease. The problem is practical. Across sub-Saharan Africa, South America, and Asia, cattle are often infected with trypanosomes—the parasites that cause sleeping sickness in humans and nagana in livestock. These same regions rely on vaccines to control foot-and-mouth disease, a highly contagious viral illness that devastates herds and trade. But trypanosomes are known to kill off B-cells, the immune cells that produce protective antibodies, and to erase immune memory. While this immunosuppression is well-documented in mice, it has never been properly characterised in cattle—the animal that actually matters for farming. If this research succeeds, it will show whether and when trypanosome infection wipes out vaccine protection. That could change how farmers and veterinarians schedule vaccinations in endemic regions—for example, treating cattle for trypanosomes before giving a prime or booster shot. The work is fundamental science in a natural host, but the payoff is actionable: better vaccination strategies that keep cattle healthier and more productive, with direct economic benefits for farming communities.
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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 cytometry for detailed NK- and B-cell subset analysis, single-cell and spatial transcriptomics to assess impact of disturbance of spleen and lymph node structure on relevant cell types, and antibody repertoire sequencing to investigate the impact of trypanosome infection upon the antigen-specific antibody response. These tools will provide an advanced understanding of key immune cell dynamics and interactions during trypanosome infection in cattle, and the extent of any impact upon the antigen-specific antibody response, the critical effector component of the humoral immune response. This will substantially progress our knowledge of trypanosome pathogenesis and immunosuppression in the natural bovine host, and translate key findings from the mouse model. Importantly, the experimental design evaluates how the timing of trypanosome infection and treatment will influence memory recall in the context of FMDV vaccination, providing potentially actionable insights for optimizing vaccination strategies in trypanosome-endemic regions - such as treatment prior to prime and/or boost vaccinations. The outputs of this research can also establish a foundation for initiating research on the interaction between trypanosomes and other pathogen coinfections and/or vaccination, a currently poorly understood area. This work aligns with BBSRC priorities for sustainable agriculture and animal health. By addressing a critical gap in understanding host-pathogen interactions and immune responses, the project outputs have the potential to improve livestock health, productivity, and deliver economic benefits to farming communities in disease-endemic regions.
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