Characterising the cytokines associated with trained innate immunity in BCG vaccinated non-human primates

Characterising the cytokines associated with trained innate immunity in BCG vaccinated non-human primates

Led by Dr Laura Sibley (UKHSA, UK)

 

The Bacille Calmette-Guerin (BCG) vaccine has been in use as the primary vaccine against tuberculosis (TB) for 100 years and is given widely at birth in countries where TB is endemic. BCG has been demonstrated to reduce infant mortality by up to 40% against unrelated childhood diseases. The mechanisms behind this are not well understood, but the hypothesis is that BCG causes epigenetic reprogramming in monocytes and NK cells, giving them memory-like characteristics that mean they can recognise and remove unrelated pathogens - a mechanism termed 'trained innate immunity'. Current research has identified cytokines produced when cells are stimulated with unrelated microorganisms including IFNγ, IL-1β and TNFα in humans and mice, and BCG vaccination is able to protect against experimental infection with Yellow Fever and Candida albicans respectively. In this pilot project, the aim is to investigate the cytokines associated with trained innate immunity induced after BCG vaccination in the non-human primate model where BCG is delivered in different ways; including BCG delivered by different routes (intradermally, intravenously, by aerosol); BCG given close to birth, to different macaque species where the efficacy conferred by BCG differs and to determine responses duration and the impacts on TB infection. At UKHSA Porton Down we have a huge archive of samples from numerous non-human primate vaccine evaluation studies which will be used to address these questions, and will enable the relationship between the responses to be revealed and the outcome following infection with Mycobacterium tuberculosis (M.tb) to be explored. The findings from this work will aid in the design of future vaccines to ensure that any novel TB vaccine to replace BCG can also induce trained immunity, so that children are not left vulnerable to these other infections if they are no longer given BCG. Analysis of the repsonses that comprise the trained immune responses after different routes and timings of BCG vaccination, will inform on how BCG is used in the future and may improve the usefulness and efficacy of BCG against TB.

Laura Sibley