USD 1.6 million to develop TB vaccine

24 September 2019• NEWSITEM

Researchers in Leiden are pioneering a new way to develop a tuberculosis vaccine. Their work is important because TB remains the deadliest infectious disease in the world. The researchers are receiving a USD 1.6 million grant from the US research funding agency National Institutes of Health to support their work.

The researchers, headed by Prof. Tom Ottenhoff and Dr Simone Joosten, are focusing on a new way to activate the immune system that they believe offers a promising path towards controlling the disease. “Tuberculosis still claims an enormous number of victims worldwide. Combined with the growing problem of antibiotic resistance, this highlights the pressing need to find new ways to prevent the disease," explains Ottenhoff. 

HLA-E protein

The research team plans to use the NIH grant to study the interaction between the immune system, small pieces of the tuberculosis bacterium and the HLA-E protein. It is the focus on HLA-E that makes this a unique project. Human leukocyte antigen (HLA) molecules are found on the surface of all human cells and present protein fragments, known as peptides, to the immune system. If the immune system recognises the peptides as foreign – for example in the case of a tuberculosis infection – it becomes activated. 

There are various types of HLA molecules, but HLA-E is special, Joosten explains. “Unlike the other types, which can vary considerably from one person to the next, HLA-E is similar in almost everyone. That means that we can develop a single vaccine that will be effective for every patient. HLA-E also provokes an unusual immune response, and it remains on the cell surface in TB patients who have an HIV infection, which is a common infection occurring together with TB.”

TB vaccine

The researchers believe that these properties make HLA-E a promising candidate as a building block for a TB vaccine. But before they can get to that point, many questions must be answered, and that is what they will be using the NIH grant for over the next four years. Which pieces of the TB bacterium should we use for the vaccine? How exactly does the immune system respond? How does the immune system recognise HLA-E in combination with the TB bacterium? And what is the most effective way to administer a vaccine of this kind?

The researchers will be working on these questions in cooperation with University of Oxford, University of Melbourne, University of Cape Town, King’s College London, Public Health England, the Biomedical Primate Research Centre, Delft University of Technology and various LUMC groups, including in Cell and Chemical Biology and Haematology.

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