Metabolic reprogramming of skin microenvironment for improved BCG vaccine efficacy

Metabolic reprogramming of skin microenvironment for improved BCG vaccine efficacy

Led by Titular Prof Francisco Javier Sánchez-García (instituto Politécnico Nacional, Mexico), with Dr Steven Smith (Brunel University, UK), Dr Barbara Kronsteiner-Dobramysl (University of Oxford, UK) and Prof Hazel Dockrell (LSHTM, UK)

 

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.

 

Project Outputs

C Angélica Pérez-Hernández et al 2020. Mitochondrial signature in human monocytes and resistance to infection in C.elegans during fumarate-induced innate immune training. Frontiers in Immunology 11: 1715

Francisco Javier Sánchez-Garcia

 

Steven Smith

 

Barbara Kronsteiner-Dobramysl

 

Hazel Dockrell