Barbara Kronsteiner-Dobramysl 2019b

Dr Barbara Kronsteiner-Dobramysl

University of Oxford, UK

Metabolic reprogramming of skin microenvironment for improved BCG vaccine efficacy (VALIDATE funded pump-priming project)

Poster Abstract

In theory, every single infectious disease could be eliminated from the earth if good vacccines (plus appropriate social and public health policies) are developed. In this scenario the best example is the vaccine against smallpox that lead to complete eradication of the disease by the year 1980.

Other vaccines, however, have not been so successful, notoriously BCG. This vaccine, first used in humans in 1921, has greatly contributed to reducing TB, but still, TB remains the world's top infectious cause of mortality.

In addition, BCG has proved to be protective in some countries but not in others.

Why is that so? Several hypotheses have been put forward and, for practical purposes, this has conducted researchers to try to develop "better anti-tuberculosis vacicnes".

Here, we propose a different approach: "current BCG is an excellent vaccine, it contains most of the potentially protective antigens. Moreover, it contains its own natural adjuvants; the problem is that we have failed to deliver it into the appropriate metabolic microenvironment".

Recent research shows that the quality of immune cell effector functions are determined by their particular metabolism at the time (i.e. how they produce energy), and that the presence of selected metabolites is capable of modifying cell immune responses locally, such as in solid tumors.

We propose to reprogramme the local cell metabolism at the site where the BCG vaccine will be delivered, to ensure the best immune cell activation and consequently, the highest protection.

Biography

I hold a doctoral degree in immunology from the University of Salzburg, Austria and have 5 years of postdoctoral research experience based at US and UK universities. Since the beginning of 2016, I am working with Prof. Susanna Dunachie at the Centre for Tropical Medicine and Global Health, University of Oxford, on defining immune correlates of survival and protection in human melioidosis as well as the susceptibility of diabetics to infection. In my current research projects I am focusing on metabolic changes in immune cells from people with diabetes and how this contributes to delayed and dysfunctional immune responses as well as poor vaccine efficacy. I am highly experienced in multicolour flow cytometry, mammalian cell culture techniques and immunological assays, work with human and mouse primary cells as well as metabolic assays including extracellular flux analysis using Seahorse.