Investigating the BCG-induced Natural Killer (NK) cell response in cattle and humans

Investigating the BCG-induced Natural Killer (NK) cell response in cattle and humans

Led by Dr Iman Satti (University of Oxford, UK), with Asst Prof Stephen Cose (UVRI, Uganda), Prof Helen McShane (University of Oxford, UK), Prof Alison Elliott (UVRI, Uganda) and Prof Jayne Hope (University of Edinburgh, UK)

 

Tuberculosis (TB) causes a huge burden of disease in humans and animals. In 2017, there were 10 million new cases of human TB and 1.6 million people died. The global prevalence of bovine TB is estimated at 7.4% of livestock. The only licensed vaccine, Bacillus Calmette Guerin (BCG), provides variable protection against human and bovine TB, particularly in high TB-burden countries. The variability in BCG efficacy has been attributed to many factors including genetic factors, coinfections, geographical location and socioeconomic status. Developing a more effective vaccine requires a better understanding of the BCG-induced immune response in populations where BCG provides good protection as well as in those where BCG is less efficacious.

Natural Killer (NK) cells are immune cells that respond early to infections but are also now recognised to contribute to a more durable immune response. There is emerging evidence for a role of NK cells in the control of TB and in vaccine-induced protection.

Here we propose to evaluate the induction of NK cells after BCG vaccination. We will utilize pre-existing samples from BCG-vaccinated humans to define the kinetics of the NK cell response. We will use samples from the UK, and two TB endemic settings, South Africa and Uganda. Any differences, in responses to BCG, between these populations may contribute to differences in protective efficacy. We have previously shown that Cytomegalovirus (CMV)+ infants who developed TB had lower expression of NK cell-associated gene signatures. We will therefore define the CMV status in our studies and determine if CMV co-infection modulates the NK cell response. We will also evaluate NK cell responses in subjects vaccinated with inhaled BCG. Parallel experiments in samples from BCG-vaccinated cattle will allow comparison between species. Understanding immune responses to BCG vaccination in different populations and species facilitates developing new improved universal TB vaccine.

 

Iman Satti

 

Steve Cose

 

Helen McShane

 

Alison Elliott

 

Jayne Hope